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Wikipedia

Prostate cancer

May 15, 2023

Cancer of the prostate[6][7] is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men.[8] The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder. It is located in the hypogastric region of the abdomen. To give an idea of where it is located, the bladder is superior to the prostate gland as shown in the image[9] The rectum is posterior in perspective to the prostate gland and the ischial tuberosity of the pelvic bone is inferior. Most prostate cancers are slow growing. Cancerous cells may spread to other areas of the body, particularly the bones and lymph nodes. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty urinating, blood in the urine, or pain in the pelvis or back. Benign prostatic hyperplasia may produce similar symptoms. Other late symptoms include fatigue, due to low levels of red blood cells.

Prostate cancer
Other namesCarcinoma of the prostate
Position of the prostate
SpecialtyOncology, urology
SymptomsNone, difficulty urinating, blood in the urine, pain in the pelvis, back, or when urinating[1][2]
Usual onsetAge > 50[3]
Risk factorsOlder age, family history, race[3]
Diagnostic methodTissue biopsy, medical imaging[2]
Differential diagnosisBenign prostatic hyperplasia[1]
TreatmentActive surveillance, surgery, radiation therapy, hormone therapy, chemotherapy[2]
Prognosisfive-year survival rate 97.1% (US)[4]
Frequency1.2 million new cases (2018)[5]
Deaths359,000 (2018)[5]

Factors that increase the risk of prostate cancer include older age, family history, and race.[3][10] About 99% of cases occur after age 50.[3] A first-degree relative with the disease increases the risk two- to three-fold.[3] Other factors include a diet high in processed meat and red meat,[3] while the risk from a high intake of milk products is inconclusive.[11] An association with gonorrhea has been found, although no reason for this relationship has been identified.[12] An increased risk is associated with the BRCA mutations.[13] Diagnosis is by biopsy.[2] Medical imaging may be done to assess whether metastasis is present.[2]

Prostate cancer screening, including prostate-specific antigen (PSA) testing, increases cancer detection but whether it improves outcomes is controversial.[3][14][15][16] Informed decision making is recommended for those 55 to 69 years old.[17][18] Testing, if carried out, is more appropriate for those with a longer life expectancy.[19] Although 5α-reductase inhibitors appear to decrease low-grade cancer risk, they do not affect high-grade cancer risk, and are not recommended for prevention.[3] Vitamin or mineral supplementation does not appear to affect risk.[3][20]

Many cases are managed with active surveillance or watchful waiting.[2] Other treatments may include a combination of surgery, radiation therapy, hormone therapy, or chemotherapy.[2] Tumors limited to the prostate may be curable.[1] Pain medications, bisphosphonates, and targeted therapy,[21] among others, may be useful.[2] Outcomes depend on age, health status and how aggressive and extensive the cancer is.[2] Most men with prostate cancer do not die from it.[2] The United States five-year survival rate is 97.1%.[4]

Globally, it is the second-most common cancer. It is the fifth-leading cause of cancer-related death in men.[22] In 2018, it was diagnosed in 1.2 million and caused 359,000 deaths.[5] It was the most common cancer in males in 84 countries,[3] occurring more commonly in the developed world.[23] Rates have been increasing in the developing world.[23] Detection increased significantly in the 1980s and 1990s in many areas due to increased PSA testing.[3] One study reported prostate cancer in 30% to 70% of Russian and Japanese men over age 60 who had died of unrelated causes.[1]

Signs and symptoms

 
A diagram of prostate cancer pressing on the urethra, which can cause symptoms
 
Prostate cancer

Early prostate cancer usually has no clear symptoms.[24] When they do appear, they are often similar to those of benign prostatic hyperplasia. These include frequent urination, nocturia (increased urination at night), difficulty starting and maintaining a steady stream of urine, hematuria (blood in the urine), dysuria (painful urination) as well as fatigue due to anemia, and bone pain.[25] One study found that about a third of diagnosed patients had one or more such symptoms.[26][27]

Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra.[28][29] Changes within the gland directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.[26]

Metastatic prostate cancer can cause additional symptoms.[30] The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs.[31] Spread of cancer into other bones such as the femur is usually to the part of the bone nearer to the prostate. Prostate cancer in the spine can compress the spinal cord, causing tingling, leg weakness, and urinary and fecal incontinence.[32]

Risk factors

The primary risk factors are obesity,[33] age, and family history. Obese men have been found to have a 34% greater death rate from prostate cancer than those with normal weight.[33] Prostate cancer is uncommon in men younger than 45, but becomes more common with advancing age.[34][35] The average age at the time of diagnosis is 70.[36]

Men with high blood pressure are more likely to develop prostate cancer.[37] A small increase in risk is associated with lack of exercise.[38] Elevated blood testosterone levels[39] may increase risk.

Genetics

Genetics affects risk, as suggested by associations with race, family, and specific gene variants.[40] Up to 10% of prostate cancer is caused by inherited genes; including 40% of early-onset prostate cancers.[41] Men with an affected first-degree relative (father or brother) have more than twice the risk of developing prostate cancer, and those with two first-degree relatives have a five-fold greater risk compared with men with no family history.[41] This risk appears to be greater for men with an affected brother than for those with an affected father.[citation needed] Increased risk also runs in some ethnic groups, with African-American men at particularly high risk – having prostate cancer at higher rates, and having more-aggressive prostate cancers.[41] In contrast, the incidence and mortality rates for Hispanic men are one-third lower than for non-Hispanic whites. Twin studies in Scandinavia suggest that 58% of prostate cancer risk can be explained by inherited factors.[42][43]

Many genes are involved in inherited risk for prostate cancer. The first gene linked to inherited prostate cancer in families was hereditary prostate cancer gene 1 (HPC1).[44][45] Mutations within the HOXB13 gene can also carry strong risk for prostate cancer.[46][47] Inherited genetic variation of the chromosome 8q24 locus, one that is prominently observed through genome-wide association study (GWAS) of both familial and sporadic prostate cancer, can carry near-Mendelian (up to 20-fold) risk for prostate cancer.[48] This region encompasses regulatory elements, non-coding genes, and the stem cell related POU5F1B gene. Roughly 4% of families in which multiple men are affected by prostate cancer carry mutations in HOXB13, and another 4% carry mutations at 8q24. Mutations in BRCA1 and BRCA2 (important risk factors for ovarian cancer and breast cancer in women) have also been implicated.[49]

Large genome-wide association studies have identified several dozen gene variants associated with increased prostate cancer risk; together the gene variants are estimated to cause around 25% of prostate cancer cases.[41] These variants include single-nucleotide polymorphisms in the vitamin D receptor common in African-Americans, and in the androgen receptor, CYP3A4, and CYP17 involved in testosterone synthesis and signaling.[41]

A number of somatic mutations (acquired rather than inherited) have also been defined in prostate tumors that drive their growth. TMPRSS2-ETS gene family fusion, specifically TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes cancer cell growth.[50] These fusions can arise via complex rearrangement chains called chromoplexy.[51]

Lifestyle

Plant-based diets are associated with a lower risk for prostate cancer. Switching to a plant-based diet shows favorable results for cancer outcomes in men with prostate cancer. Especially vegan diets consistently show favorable associations with prostate cancer risk and outcomes.[52]

People who consume high levels of dietary fats are at an increased risk of developing symptomatic prostate cancer, as are those who consume high levels of polycyclic aromatic hydrocarbons (from cooking red meats).[41] Those with a diet rich in cruciferous vegetables, genistein, and lycopene (found in tomatoes) are at a reduced risk of symptomatic prostate cancer.[41]

Several dietary supplements have been studied and found not to impact prostate cancer risk, including selenium, vitamin C, and vitamin E.[53]

The consumption of milk may be related to prostate cancer.[54][55] A 2020 systematic review found the results on milk consumption and prostate cancer inconclusive but stated that individuals with higher risk may reduce or eliminate milk.[56] A 2019 overview stated that the evidence that linked milk to higher rates of prostate cancer was inconsistent and inconclusive.[57]

Lower blood levels of vitamin D may increase risks.[58]

The data on the relationship between diet and prostate cancer are poor.[59] However, the rate of prostate cancer is linked to the consumption of the Western diet.[59] Little if any evidence associates trans fat, saturated fat, and carbohydrate intake and prostate cancer.[59][60] Evidence does not support a role for omega-3 fatty acids in preventing prostate cancer.[59][61] Vitamin supplements appear to have no effect and some may increase the risk.[20][59] High supplemental calcium intake has been linked to advanced prostate cancer.[62]

Fish may lower prostate-cancer deaths, but does not appear to affect occurrence.[63] Some evidence supports lower rates of prostate cancer with a vegetarian diet,[64] lycopene, selenium[65][66] cruciferous vegetables, soy, beans and/or other legumes.[67]

Regular exercise may slightly lower risk, especially vigorous activity.[67][68]

Medication exposure

Some links have been established between prostate cancer and medications, medical procedures, and medical conditions.[69] Statins may also decrease risk.[70]

Infection

Prostatitis (infection or inflammation) may increase risk. In particular, infection with the sexually transmitted infections Chlamydia, gonorrhea, or syphilis seems to increase risk.[12][71]

Papilloma virus has been proposed to have a potential role, but as of 2015, the evidence was inconclusive;[72] as of 2018, the increased risk was debated.[73]

Environment

US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.[74]

Sex

Although some evidence from prospective cohort studies indicates that frequent ejaculation may reduce prostate cancer risk,[75] no randomized controlled trials reported this benefit.[76] An association between vasectomy and prostate cancer was found, but causality has not been established.[77]

Pathophysiology

 

The prostate is part of the male reproductive system that helps make and store seminal fluid. In adult men, a typical prostate is about 3 cm long and weighs about 20 g.[78] It is located in the pelvis, under the urinary bladder and in front of the rectum. The prostate surrounds part of the urethra, the tube that carries urine from the bladder during urination and semen during ejaculation.[79] The prostate contains many small glands, which make about 20% of the fluid constituting semen.[80]

Superiorly, the prostate base is contiguous with the bladder outlet. Inferiorly, the prostate's apex heads in the direction of the urogenital diaphragm, which is pointed anterio-inferiorly.[81] The prostate can be divided into four anatomic spaces: peripheral, central, transitional, and anterior fibromuscular stroma.[82] The peripheral space contains the posterior and lateral portions of the prostate, as well as the inferior portions of the prostate.[83] The central space contains the superior portion of the prostate including the most proximal aspects of the urethra and bladder neck.[84] The transitional space is located just anterior to the central space and includes urethra distal to the central gland urethra.[85] The neurovascular bundles course along the posterolateral prostate surface and penetrate the prostatic capsule there as well.[86]

Most of the glandular tissue is found in the peripheral and central zones (peripheral zone: 70-80% of glandular tissue; central zone: 20% of glandular tissue).[87] Some is found in the transitional space (5% of glandular tissue). Thus, most cancers that develop from glandular tissue are found in the peripheral and central spaces,[88] while about 5% is found in the transitional space. None is found in the anterior fibromuscular stroma since no glands are in that anatomic space.

The prostate glands require male hormones, known as androgens, to work properly. Androgens include testosterone, which is made in the testes;[89] dehydroepiandrosterone, made in the adrenal glands; and dihydrotestosterone, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass.[citation needed]

Because of the prostate's location, prostate diseases often affect urination, ejaculation, and rarely defecation. In prostate cancer, the cells of these glands mutate into cancer cells.[90]

 
Prostate cancer that has metastasized to the lymph nodes
 
Prostate cancer that has metastasized to the bone

Most prostate cancers are classified as adenocarcinomas, or glandular cancers, that begin when semen-secreting gland cells mutate into cancer cells.[91] The region of the prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain within otherwise normal prostate glands, a condition known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN).[92] Although no proof establishes that PIN is a cancer precursor, it is closely associated with cancer.[93] Over time, these cells multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor.

Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or tumor cells may develop the ability to travel in the bloodstream and lymphatic system.[94]

Prostate cancer is considered a malignant tumor because it can invade other areas of the body. This invasion is called metastasis.[95] Prostate cancer most commonly metastasizes to the bones and lymph nodes, and may invade the rectum, bladder, and lower ureters after local progression.[96] The route of metastasis to bone is thought to be venous, as the prostatic venous plexus draining the prostate connects with the vertebral veins.[97]

The prostate is a zinc-accumulating, citrate-producing organ. Transport protein ZIP1 is responsible for the transport of zinc into prostate cells.[98] One of zinc's important roles is to change the cell's metabolism to produce citrate, an important semen component.[99] The process of zinc accumulation, alteration of metabolism, and citrate production is energy inefficient, and prostate cells require enormous amounts of energy (ATP) to accomplish this task. Prostate cancer cells are generally devoid of zinc. Prostate cancer cells save energy by not making citrate, and use the conserved energy to grow, reproduce and spread.[100]

The absence of zinc is thought to occur via silencing the gene that produces ZIP1. It is called a tumor suppressor gene product for the gene SLC39A1. The cause of the epigenetic silencing is unknown.[101] Strategies that transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits NF-κB pathways, is antiproliferative, and induces apoptosis in abnormal cells.[102] Unfortunately, oral ingestion of zinc is ineffective since high concentrations of zinc into prostate cells is not possible without ZIP1.[98]

Loss of cancer suppressor genes, early in prostatic carcinogenesis, have been localized to chromosomes 8p, 10q, 13q, and 16q. P53 mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings, hence, p53 mutations are a late event in the pathology. Other tumor suppressor genes that are thought to play a role include PTEN and KAI1. "Up to 70 percent of men with prostate cancer have lost one copy of the PTEN gene at the time of diagnosis".[103] Relative frequency of loss of E-cadherin and CD44 has also been observed. Loss of the retinoblastoma (RB) protein induces androgen receptor deregulation in castration-resistant prostate cancer by deregulating 'E2F1 expression.[104]

The factors that drive disease progression and clinical prognosis remain only partly understood but a variety of molecular determinants has been identified that appear to be involved. The most important of these might be the tyrosine phosphatase ACP1 of which the expression might outperform the Gleason grading system for predicting disease course.[105] Other molecules identified include the transcription factor RUNX2 which may prevent cancer cells from undergoing apoptosis,[106] the PI3k/Akt signaling cascade in conjunction with the transforming growth factor beta/SMAD signaling cascade that also protect against apoptosis.[107] Pim-1 is upregulated in prostate cancer.[21] X-linked inhibitor of apoptosis (XIAP) is hypothesized to promote cancer cell survival and growth,[108] the Macrophage inhibitory cytokine-1 (MIC-1) that stimulates the focal adhesion kinase (FAK) signaling pathway.[109] Nevertheless, it is fair to say that the molecular factors that determine why some patients have quiescent disease while others display prognosis, remain largely obscure.

The androgen receptor helps cancer cells to survive.[110] Prostate-specific membrane antigen (PSMA) stimulates cancer development by increasing folate levels, helping the cancer cells to survive and grow; it increases available folates for use by hydrolyzing glutamated folates.[111]

Screening

Main article: Prostate cancer screening

Prostate cancer screening searches for cancers in those without symptoms. Options include the digital rectal exam and the PSA blood test.[112] Such screening is controversial,[113] and for many, may lead to unnecessary disruption and possibly harmful consequences.[114] Harms of population-based screening, primarily due to overdiagnosis (the detection of latent cancers that would have otherwise not been discovered) may outweigh the benefits.[112] Others recommend shared decision-making, an approach where screening may occur after a physician consultation.[115]

The United States Preventive Services Task Force (USPSTF) suggests the decision whether to have PSA screening be based on consultation with a physician for men 55 to 69 years of age.[15] USPSTF recommends against PSA screening after age 70.[17] The Centers for Disease Control and Prevention endorsed USPSTF's conclusion.[116] The American Society of Clinical Oncology and the American College of Physicians discourage screening for those who are expected to live less than 10–15 years, while those with a greater life expectancy a decision should individually balance the potential risks and benefits.[117] In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment."[118]

American Urological Association (AUA 2013) guidelines call for weighing the uncertain benefits of screening against the known harms associated with diagnostic tests and treatment.[119] The AUA recommends that shared decision-making should control screening for those 55 to 69, and that screening should occur no more often than every two years.[120] In the United Kingdom as of 2018, no program existed to screen for prostate cancer.[16]

The American Cancer Society's position regarding early detection by PSA testing is:

Research has not yet proven that the potential benefits of testing outweigh the harms of testing and treatment. The American Cancer Society believes that men should not be tested without learning about what we know and don't know about the risks and possible benefits of testing and treatment. Starting at age 50, (45 if African American or brother or father suffered from condition before age 65) talk to your doctor about the pros and cons of testing so you can decide if testing is the right choice for you."[121]

Diagnosis

 
Prostate needle biopsy
 
If already having grown large, a prostate cancer may first be detected on CT scan.

Several tests can be used to gather information about the prostate and the urinary tract. Digital rectal examination may allow a doctor to detect prostate abnormalities.[122] Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted in the urethra.[123]

A diagnosis of prostate cancer requires a biopsy of the prostate be taken and examined under a microscope by a pathologist. Prostate biopsies are typically taken by a needle guided by imaging – either transrectal ultrasound, magnetic resonance imaging (MRI), or a combination of the two.[124] During a biopsy, a urologist or radiologist obtains tissue samples from the prostate via either the rectum or the perineum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second.[125] Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization.[126]

Ultrasound imaging can be obtained transrectally and is used during prostate biopsies.[127] Prostate cancer can be seen as a hypoechoic lesion in 60% of cases. The other 40% of cancerous lesions are either hyperechoic or isoechoic. On Color Doppler, the lesions appear hypervascular.[128]

Antibiotics should be used to prevent complications such as fever, urinary tract infections, and sepsis[129] even if the most appropriate course or dose is undefined.[130] About 55% of men report discomfort during prostate biopsy.[131]

Biopsies are examined under a microscope by a pathologist, who determines the type and extent of cancerous cells present. Cancers are first classified based on their appearance under a microscope. Over 95% of prostate cancers are classified as adenocarcinomas (resembling gland tissue), with the rest largely squamous-cell carcinoma (resembling squamous cells, a type of epithelial cell) and transitional cell carcinoma (resembling transitional cells).[132] Tumor samples can be stained for the presence of PSA and other tumor markers to determine the origin of malignant cells that have metastasized.[133]

Next tumor samples are graded based on how much the tumor tissue differs from normal prostate tissue; the more different the tumor appears, the faster the tumor is likely to grow. The Gleason grading system is commonly used, where the pathologist assigns a number from 1 (similar to prostate tissue) to 5 (least similar) for the most common pattern observed under the microscope, then does the same for the second-most common pattern. The sum of these two numbers is the Gleason score.[132] The total scores of 2 through 5 are no longer commonly used in practice, making the lowest score 6, and the highest score 10. Scores are commonly grouped into Gleason grade groups: a score of 6 or lower is Gleason grade group 1; a score of 7 with the first number (from the most common pattern) 3 and the second number 4 is grade group 2; the reverse – first number 4, second number 3 – is grade group 3; a score of 8 is grade group 4; a score of 9 or 10 is grade group 5.[132] Higher Gleason scores and higher grade groups represent cancer cases likely to be more aggressive with worse prognosis.[132]

 
Micrograph showing a prostate cancer (conventional adenocarcinoma) with perineural invasion. H&E stain.

Staging

Main article: Prostate cancer staging
 
Diagram showing T1-3 stages of prostate cancer.

After diagnosis of prostate cancer, the tumor is staged to determine the extent of tumor growth and spread. Prostate cancer is typically staged using the American Joint Committee on Cancer's (AJCC) three-component TNM system, with scores assigned for the extent of the tumor (T), spread to any lymph nodes (N), and the presence of metastases (M).[135] Scores of T1 and T2 represent tumors that remain within the prostate: T1 is for tumors not detectable by imaging or digital rectal exam; T2 is for tumors detectable by imaging or rectal exam, but still confined within the prostate.[136] T3 is for tumors that grow beyond the prostate – T3a is for tumors with any extension outside the prostate; T3b is for tumors that invade the adjacent seminal vesicles. T4 is for tumors that have grown into organs beyond the seminal vesicles.[136] The N and M scores are binary. N1 represents any spread to the nearby lymph nodes. M1 represents any metastases to other body sites.[136]

The AJCC then combines the TNM scores, Gleason grade group, and results of the PSA blood test to categorize cancer cases into one of four stages, and their subdivisions. Cancer cases with localized tumors (T1 or T2), no spread (N0 and M0), Gleason grade group 1, and PSA less than 10 ng/mL are designated stage I. Those with localized tumors, no spread, and PSA between 10 and 20 ng/mL are desigated stage II – subdivided into IIA for Gleason grade group 1, IIB for grade group 2, and IIC for grade group 3 or 4. Stage III is the designation for any of three higher risk factors: IIIA is for a PSA level about 20 ng/mL; IIIB is for T3 or T4 tumors; IIIC is for a Gleason grade group of 5. Stage IV is for cancers that have spread to lymph nodes (N1, stage IVA) or other organs (M1, stage IVB).[135]

In the United Kingdom the Cambridge Prognostic Group (CPG) is used for categorising prostate cancer into 5 risk groups (CPG1 to CPG5).[137]

Several tests can be used to look for evidence of spread. Medical specialty professional organizations, including the American Urological Association and European Association of Urology, recommend against the use of PET scans, CT scans, or bone scans when a physician stages early prostate cancer with low risk for metastasis.[138][139][140][141][142] Those tests would be appropriate in cases such as when a CT scan evaluates spread within the pelvis, a bone scan looks for spread to the bones, and endorectal coil magnetic resonance imaging evaluates the prostatic capsule and the seminal vesicles. Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis—the reverse of what is found in many other metastatic cancers.[143] Approved radiopharmaceutical diagnostic agents used in PET: fluciclovine (2016), Ga 68 PSMA-11 (2020), piflufolastat (2021).

In men with high-risk localised prostate cancer, staging with PSMA PET/CT may be appropriate to detect nodal or distant metastatic spread. In 2020, a randomised phase 3 trial compared Gallium-68 PSMA PET/CT to standard imaging (CT and bone scan). It reported superior accuracy of Gallium-68 PSMA-11 PET/CT (92% vs 65%), higher significant change in management (28% vs 15%), less equivocal/uncertain imaging findings (7% vs 23%) and lower radiation exposure (10 msV vs 19 mSv). The study concluded that PSMA PET/CT is a suitable replacement for conventional imaging.[144]

A PSMA scan is a positron emission tomography (PET) imaging technique which targets the overexpression of PSMA in prostate cancer tissue. A range of radiopharmaceuticals have been developed, with more under active research. Gallium-68 (68Ga) PSMA-11 and fluorine-18 (18F) PSMA-DCFPyL received FDA approval for PET-CT imaging in prostate cancer in 2021.[145][146] It has a role in evaluation of prostate cancer patients, especially patients who may go on to receive lutetium-177 (177Lu) PSMA radioligand therapy.[147][148]

  •  

    Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)

  •  

    Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)

  •  

    Sclerosis of the bones of the pelvis due to prostate cancer metastases

Prevention

No drug or vaccine is approved by regulatory agencies for the prevention of prostate cancer. Several studies have shown 5α-reductase inhibitors to reduce the incidence of prostate cancer; however, whether they reduce disease is not clear.[53]

Management

Main article: Management of prostate cancer

The first decision is whether treatment is needed. Low-grade forms found in elderly men often grow so slowly that treatment is not required.[149] Treatment may be inappropriate if a person has other serious health problems or is not expected to live long enough for symptoms to appear. Approaches in which treatment is postponed are termed "expectant management".[149] Expectant management is divided into two approaches: Watchful waiting, which has palliative intent (aims to treat symptoms only), and active surveillance, which has curative intent (aims to prevent the cancer from advancing).[149]

Which option is best depends on disease stage, the Gleason score, and the PSA level. Other important factors are age, general health and a person's views about potential treatments and their possible side effects. Because most treatments can have significant side effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. A 2017 review found that more research focused on person-centered outcomes is needed to guide patients.[150] A combination of treatment options is often recommended.[151][152][153]

Guidelines for specific clinical situations require estimation of life expectancy.[154] As average life expectancy increases due to advances in the treatment of other diseases, more patients will live long enough for their prostate cancer to express symptoms.[155] An 18-item questionnaire was proposed to learn whether patients have adequate knowledge and understanding of their treatment options. In one 2015 study, most of those who were newly diagnosed correctly answered fewer than half of the questions.[154]

The widespread use of PSA screening in the US has resulted in diagnosis at earlier age and cancer stage, but almost all cases are still diagnosed after age 65, while about 25% are diagnosed after age 75.[156] Though US National Comprehensive Cancer Network guidelines recommend using life expectancy to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as radical prostatectomy or radiation therapy and are instead treated with hormonal therapy or watchful waiting.[157]

Surveillance

Main article: Active surveillance of prostate cancer

Many men diagnosed with low-risk prostate cancer are eligible for active surveillance. The tumor is carefully observed over time, with the intention of initiating treatment if signs of progression appear.[158] Active surveillance is not synonymous with watchful waiting, a term which implies no treatment or specific program of monitoring, with the assumption that only palliative treatment would be used if advanced, symptomatic disease develops.[149]

Active surveillance involves monitoring the tumor for growth or symptoms, which trigger treatment. The monitoring process may involve PSA tests, digital rectal examination, or repeated biopsies every few months.[159] The goal of active surveillance is to postpone treatment, and avoid overtreatment and its side effects, given a slow-growing or self-limited tumor that in most people is unlikely to cause problems.[160] This approach is not used for aggressive cancers, and may cause anxiety for people who wrongly believe that all cancers are deadly or that their condition is life-threatening.[161] Between 50 and 75% of patients die from other causes without experiencing prostate symptoms.[162] In localized disease, based on long-term follow-up, radical prostatectomy results in significantly improved oncological outcomes when compared with watchful waiting.[163] Prostatectomy is associated with increased rates of urinary incontinence and erectile dysfunction, but these findings are based primarily on men diagnosed before widespread PSA screening and cannot be highly generalized.[163] When compared to active monitoring/surveillance, on follow-up at ten years, radical prostatectomy probably has similar outcomes for disease-specific survival and probably reduces risk of disease progression and spreading.[163] Urinary and sexual function are probably decreased in patients treated with radical prostatectomy.[163]

Active treatment

Both surgical and nonsurgical treatments are available, but treatment can be difficult, and combinations can be used.[164] Treatment by external beam radiation therapy, brachytherapy, cryosurgery, high-intensity focused ultrasound, and prostatectomy are, in general, offered to men whose cancer remains within the prostate.[165] Hormonal therapy and chemotherapy are often reserved for metastatic disease. Exceptions include local or metastasis-directed therapy with radiation may be used for advanced tumors with limited metastasis.[166] Hormonal therapy is used for some early-stage tumors. Cryotherapy (the process of freezing the tumor), hormonal therapy, and chemotherapy may be offered if initial treatment fails and the cancer progresses.[167] Sipuleucel-T, a cancer vaccine, was reported to offer a four-month increase in survival in metastatic prostate cancer,[168] but the marketing authorisation for it was withdrawn on 19 May 2015.

If radiation therapy fails, radical prostatectomy may be an option,[169] though it is a technically challenging surgery.[170] However, radiation therapy after surgical failure may have many complications.[171] It is associated with a small increase in bladder and colon cancer.[172] Radiotherapy and surgery appear to result in similar outcomes with respect to bowel, erectile and urinary function after five years.[173]

Nonsurgical treatment

Non-surgical treatment may involve radiation therapy, chemotherapy, hormonal therapy, external beam radiation therapy, and particle therapy, high-intensity focused ultrasound, or some combination.[174][175]

Prostate cancer that persists when testosterone levels are lowered by hormonal therapy is called castrate-resistant prostate cancer (CRPC).[176][177] Many early-stage cancers need normal levels of testosterone to grow, but CRPC does not. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term CRPC emerged because these cancers show reliance upon hormones, particularly testosterone, for androgen receptor activation.[178][179]

The cancer chemotherapeutic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months.[180][181] A second-line chemotherapy treatment is cabazitaxel.[182] A combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective in the treatment of CRPC.[183]

Immunotherapy treatment with sipuleucel-T in CRPC appeared to increase survival by four months.[184] However, marketing authorisation for sipuleucel-T was withdrawn on 19 May 2015. The second line hormonal therapy abiraterone increases survival by about 4.6 months.[185] Enzalutamide is another second line hormonal agent with a five-month survival advantage. Both abiraterone and enzalutamide are currently in clinical trials in those with CRPC who have not previously received chemotherapy.[186][187]

Not all patients respond to androgen signaling-blocking drugs. Certain cells with characteristics resembling stem cells remain unaffected.[188][189] Therefore, the desire to improve CRPC outcomes resulted in increasing doses or combination therapy with synergistic androgen-signaling blocking agents.[190] But even these combination will not affect stem-like cells that do not exhibit androgen signaling.[191]

For patients with metastatic prostate cancer that has spread to their bones, doctors use a variety of bone-modifying agents to prevent skeletal complications and support the formation of new bone mass.[192] Zoledronic acid (a bisphosphonate) and denosumab (a RANK-ligand-inhibitor) appear to be effective agents, but are associated with more frequent and serious adverse events.[192]

Surgery

Radical prostatectomy is considered the mainstay of surgical treatment of prostate cancer, where the surgeon removes the prostate, seminal vesicles, and surrounding lymph nodes.[193] It can be done by an open technique (a skin incision at the lower abdomen), or laparoscopically. Radical retropubic prostatectomy is the most commonly used open surgical technique.[194] Robotic-assisted prostatectomy has become common.[195] Men with localized prostate cancer, having laparoscopic radical prostatectomy or robotic-assisted radical prostatectomy, might have shorter stays in the hospital and get fewer blood transfusions than men undergoing open radical prostatectomy.[196] How these treatments compare with regard to overall survival or recurrence-free survival is unknown.[196]

Transurethral resection of the prostate is the standard surgical treatment for benign enlargement of the prostate.[195] In prostate cancer, this procedure can be used to relieve symptoms of urinary retention caused by a large prostate tumor, but it is not used to treat the cancer itself. The procedure is done under spinal anesthesia, a resectoscope is inserted inside the penis and the extra prostatic tissue is cut to clear the way for the urine to pass.[90]

Uses of MRI

Prostate MRI is also used for surgical planning for robotic prostatectomy.[197] It helps surgeons decide whether to resect or spare the neurovascular bundle, determine return to urinary continence, and help assess surgical difficulty.[197] MRI is used in other types of treatment planning, for both focal therapy[198] and radiotherapy.[199] MRI can also be used to target areas for research sampling in biobanking.[200][201]

Complications

The two main complications encountered after prostatectomy and prostate radiotherapy are erectile dysfunction and urinary incontinence, mainly stress-type. Most men regain continence within 6 to 12 months after the operation, so doctors usually wait at least one year before resorting to invasive treatments.[202]

Stress urinary incontinence usually happens after prostate surgery or radiation therapy due to factors that include damage to the urethral sphincter or surrounding tissue and nerves.[203] The prostate surrounds the urethra, a muscular tube that closes the urinary bladder.[204] Any of the mentioned reasons can lead to incompetent closure of the urethra and hence incontinence.[205] Initial therapy includes bladder training, lifestyle changes, kegel exercises, and the use of incontinence pads. More invasive surgical treatment can include the insertion of a urethral sling or an artificial urinary sphincter, which is a mechanical device that mimics the function of the urethral sphincter, and is activated manually by the patient through a switch implanted in the scrotum.[206] The latter is considered the gold standard in patients with moderate or severe stress urinary incontinence.[207]

Erectile dysfunction happens in different degrees in nearly all men who undergo prostate cancer treatment, including radiotherapy or surgery; however, within one year, most of them will notice improvement. If nerves were damaged, this progress may not take place. Pharmacological treatment includes PDE-5 inhibitors such as viagra or cialis, or injectable intracavernous drugs injected directly into the penis (prostaglandin E1 and vasoactive drug mixtures). Other nonpharmacological therapy includes vacuum constriction devices and penile implants.[208]

Psychological

Psychological interventions such as psychoeducation, cognitive behavioural therapy (CBT) and mindfulness are recommended for the management of mental and emotional complications of disease symptoms and those associated with active treatment.[209][210] Due to limited research and inadequate methodological rigor of published literature, solid recommendations cannot be made on the effectiveness of mindfulness in men with prostate cancer.[211]

Prognosis

Many prostate cancers are not destined to be lethal, and most men will ultimately not die as a result of the disease. Mortality varies widely across geography and other elements. In the United States, five-year survival rates range from 29% (distant metastases) to 100% (local or regional tumors).[212] In Japan, the fatality rate rose to 8.6/100,000 in 2000.[213] In India in the 1990s, half of those diagnosed with local cancer died within 19 years.[214] One study reported that African-Americans have 50–60 times more deaths than found in Shanghai, China.[215] In Nigeria, 2% of men develop prostate cancer, and 64% of them are dead after 2 years.[216] Most Nigerian men present with metastatic disease with a typical survival of 40 months.[217]

In patients who undergo treatment, the most important clinical prognostic indicators of disease outcome are the stage, pretherapy PSA level, and Gleason score.[218] The higher the grade and the stage, the poorer the prognosis. Nomograms can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients.[219] A complicating factor is that the majority of patients have multiple independent tumor foci upon diagnosis, and these foci have independent genetic changes and molecular features.[220] Because of this extensive inter-focal heterogeneity, it is a risk that the prognostication is set based on the wrong tumor focus.

An important aspect of decision making on the value of treatment is how to balance prognosis from prostate cancer with other causes of mortality and the morbidity of treatment. The PREDICT Prostate algorithm[221] is a multivariable prognostic model that provides individualised cancer-specific and overall long-term survival estimates in early stage non-metastatic PCa patients.[222] In addition to the use of routinely available preoperative clinical-pathological variables such as PSA, biopsy Gleason score (ISUP grade group), and clinical T-stage, the PREDICT Prostate tool also includes the impact of patient characteristics (age and comorbidity status) and radical treatment (radical prostatectomy or radiotherapy) on survival. The tool provides patients with estimated survival rates after treatment in the context of absolute mortality rate, which allows patients to make an informed decision as to the value of treatment and its potential side effects. Thurtle et al.[223] performed an external validation of their previously published PREDICT Prostate model.[224] The tool outperformed other widely used models and was proven to have high c-indices for all-cause and PCa-specific mortality, and the model calibration was good and remained accurate within the treatment subgroups. Recent work has also shown that it significantly alters clinician treatment recommendations and improves patients confidence in decision making and in their understanding of mortality risks from a new prostate cancer diagnosis [225][226] Predict Prostate is endorsed for use as a decision aid for prostate cancer by the UK National Institute for Health and Care Excellence [227]

Androgen ablation therapy causes remission in 80–90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission, an androgen-independent phenotype typically emerges, wherein the median overall survival is 23–37 months from the time of initiation of androgen ablation therapy.[228] How androgen-independence is established and how it re-establishes progression is unclear.[229]

Classification systems

 
Micrograph of prostate adenocarcinoma, acinar type, the most common type of prostate cancer. Needle biopsy, H&E stain

Several tools are available to help predict outcomes, such as pathologic stage and recurrence after surgery or radiation therapy. Most combine stage, grade, and PSA level, and some include the number or percentage of biopsy cores positive, age, and/or other information.

  • The D'Amico classification stratifies men by low, intermediate, or high risk based on stage, grade and PSA. It is used widely in clinical practice and research settings.[230] The major downside to the three-level system is that it does not account for multiple adverse parameters (e.g., high Gleason score and high PSA) in stratifying patients.
  • The Partin tables[231] predict pathologic outcomes (margin status, extraprostatic extension, and seminal vesicle invasion) based on the same three variables and are published as lookup tables.
  • The Kattan nomograms predict recurrence after surgery and/or radiation therapy, based on data available at the time of diagnosis or after surgery.[232] The Kattan score represents the likelihood of remaining free of disease at a given time interval following treatment.
  • The UCSF Cancer of the Prostate Risk Assessment (CAPRA) score predicts both pathologic status and recurrence after surgery. It offers accuracy comparable to the Kattan preoperative nomogram and can be calculated without tables or a calculator. Points are assigned based on PSA, grade, stage, age, and percentage of cores positive; the sum yields a 0–10 score, with every two points representing roughly a doubling of risk of recurrence. The CAPRA score was derived from community-based data in the CaPSURE database.[233] It has been validated among over 10,000 prostatectomy patients, including patients from CaPSURE;[234] the SEARCH registry, representing data from several Veterans Health Administration and military medical centers;[235] a multi-institutional cohort in Germany;[236] and the prostatectomy cohort at Johns Hopkins University.[237] More recently, it has been shown to predict metastasis and mortality following prostatectomy, radiation therapy, watchful waiting, or androgen deprivation therapy.[238]
  • The UK National Institute for Health and Care Excellence guidelines recommends use of the Cambridge Prognostic Groups (CPG) 5-tier model when determining treatment options. The rationale for the change related to recent evidence, which suggests that 5-tier risk stratification model was better at predicting prostate cancer specific mortality than older 3-tier models [239] The CPG model has been tested and validated in studies including >80,000 men [240][241][242] The NICE CPG model and treatment recommendations can be viewed at the NICE guideline website.[243]

Life expectancy

Life expectancy projections are averages for an entire male population, and many medical and lifestyle factors modify these numbers.[244] For example, studies have shown that a 40-year-old man will lose 3.1 years of life if he is overweight (BMI 25–29) and 5.8 years of life if he is obese (BMI 30 or more), compared to men of normal weight. If he is both overweight and a smoker, he will lose 6.7 years, and if obese and a smoker, he will lose 13.7 years.[245]

No evidence shows that either surgery or beam radiation has an advantage over the other in this regard. The lower death rates reported with surgery appear to occur because surgery is more likely to be offered to younger men with less severe cancers. Insufficient information is available to determine whether seed radiation extends life more readily than the other treatments, but data so far do not suggest that it does.[246]

Men with low-grade disease (Gleason 2–4) were unlikely to die of prostate cancer within 15 years of diagnosis.[247] Older men (age 70–75) with low-grade disease had a roughly 20% overall survival at 15 years due to deaths from competing causes. Men with high-grade disease (Gleason 8–10) experienced high mortality within 15 years of diagnosis, regardless of their age.[248]

Epidemiology

 
Age-standardized death from prostate cancer per 100,000 inhabitants in 2004.[249]
  no data
  <4
  4–8
  8–12
  12–16
  16–20
  20–24
  24–28
  28–32
  32–36
  36–40
  40–44
  >44

As of 2012, prostate cancer is the second-most frequently diagnosed cancer (at 15% of all male cancers)[250] and the sixth leading cause of cancer death in males worldwide.[251] In 2010, prostate cancer resulted in 256,000 deaths, up from 156,000 deaths in 1990.[252] Rates of prostate cancer vary widely. Rates vary widely between countries. It is least common in South and East Asia, and more common in Europe, North America, Australia, and New Zealand.[253] Prostate cancer is least common among Asian men and most common among Black men, with white men in between.[254][255]

Prostate cancer is common with age, but a minority of men with prostate cancer will ever have symptoms of the disease or have their prostate cancer diagnosed. More than 70% of men autopsied in their 70s have cancer in their prostate; however, 1 in 8 men are diagnosed with prostate cancer. Of those with prostate cancer, around 2% die of the disease.[256]

United States

 
New cases and deaths from prostate cancer in the United States per 100,000 males between 1975 and 2014

Prostate cancer is the third-leading cause of cancer death in men, exceeded by lung cancer and colorectal cancer. It accounts for 19% of all male cancers and 9% of male cancer-related deaths.[257]

Cases ranged from an estimated 230,000 in 2005[258] to an estimated 164,690 In 2018.[259]

Deaths held steady around 30,000 in 2005[258] and 29,430 in 2018.

Age-adjusted incidence rates increased steadily from 1975 through 1992, with particularly dramatic increases associated with the spread of PSA screening in the late 1980s, later followed by a fall in incidence. A decline in early-stage incidence rates from 2011 to 2012 (19%) in men aged 50 years and older persisted through 2013 (6%).

Declines in mortality rates in certain jurisdictions may reflect the interaction of PSA screening and improved treatment.[260] The estimated lifetime risk is about 14.0%, and the lifetime mortality risk is 2.6%.[261]

Between 2005 and 2011, the proportion of disease diagnosed at a locoregional stage was 93% for whites and 92% for African Americans;[262] the proportion of disease diagnosed at a late stage was 4% for European Americans and 5% for African Americans.[262]

Prostate cancer is more common in the African American population than the European American population.[3] An autopsy study of White and Asian men also found an increase in occult prostate cancer with age,[263] reaching nearly 60% in men older than 80 years. More than 50% of cancers in Asian men and 25% of cancers in White men had a Gleason score of 7 or greater,[264] suggesting that Gleason score may be an imprecise indicator of clinically insignificant cases.[265]

Canada

Prostate cancer is the third-leading type of cancer in Canadian men. In 2016, around 4,000 died and 21,600 men were diagnosed with prostate cancer.[113]

Europe

In Europe in 2012, it was the third-most diagnosed cancer after breast and colorectal cancers at 417,000 cases.[266]

In the United Kingdom, it is the second-most common cause of cancer death after lung cancer, where around 35,000 cases are diagnosed every year, of which around 10,000 are fatal.[267]

History

The prostate was first described by Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538.[268] Prostate cancer was identified in 1853.[269][270] It was initially considered a rare disease, probably because of shorter life expectancies and poorer detection methods in the 19th century. The first treatments were surgeries to relieve urinary obstruction.[271]

Removal of the gland was first described in 1851,[272] and radical perineal prostatectomy was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital.[273][269]

Surgical removal of the testes (orchiectomy) to treat prostate cancer was first performed in the 1890s, with limited success.[274] Transurethral resection of the prostate (TURP) replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh.[275] This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function.

In 1941, Charles B. Huggins published studies in which he used estrogen to oppose testosterone production in men with metastatic prostate cancer. This discovery of "chemical castration" won Huggins the 1966 Nobel Prize in Physiology or Medicine.[276] The role of the gonadotropin-releasing hormone (GnRH) in reproduction was determined by Andrzej W. Schally and Roger Guillemin, who shared the 1977 Nobel Prize in Physiology or Medicine for this work. GnRH receptor agonists, such as leuprorelin and goserelin, were subsequently developed and used to treat prostate cancer.[277][278]

Radiation therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium implants. External beam radiotherapy became more popular as stronger [X-ray] radiation sources became available in the middle of the 20th century. Brachytherapy with implanted seeds (for prostate cancer) was first described in 1983.[279]

Systemic chemotherapy for prostate cancer was first studied in the 1970s. The initial regimen of cyclophosphamide and 5-fluorouracil was quickly joined by regimens using other systemic chemotherapy drugs.[280]

Enzalutamide gained FDA approval in 2012 for the treatment of castration-resistant prostate cancer (CRPC).[186][187] Alpharadin won FDA approval in 2013, under the priority review program.[281]

In 2006, a previously unknown retrovirus, Xenotropic MuLV-related virus (XMRV), was associated with human prostate tumors,[282] but PLOS Pathogens retracted the article in 2012.[282]

Society and culture

Men with prostate cancer generally encounter significant disparities in awareness, funding, media coverage, and research—and therefore, inferior treatment and poorer outcomes—compared to other cancers of equal prevalence.[283] In 2001, The Guardian noted that Britain had 3,000 nurses specializing in breast cancer, compared to a single nurse for prostate cancer.[284] Waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer.[285]

A 2007 report by the U.S.-based National Prostate Cancer Coalition stated that prostate cancer drugs were outnumbered seven to one by breast cancer drugs.[286] The Times also noted an "anti-male bias in cancer funding" with a four-to-one discrepancy in the United Kingdom by both the government and by cancer charities such as Cancer Research UK.[283][287] Critics cite such figures when claiming that women's health is favored over men's health.[288]

Disparities extend into detection, with governments failing to fund or mandate prostate cancer screening while fully supporting breast cancer programs. For example, a 2007 report found 49 U.S. states mandate insurance coverage for routine breast cancer screening, compared to 28 for prostate cancer.[289]

Prostate cancer experiences significantly less media coverage than other, equally prevalent cancers, outcovered 2.6:1 by breast cancer.[283]

Prostate Cancer Awareness Month takes place in September in a number of countries. A light blue ribbon is used to promote the cause.[290][291]

Research

Castration-resistant prostate cancer

Castration-resitant prostate cancer is prostate cancer that progresses despite androgen depletion therapy.[292]

Enzalutamide is a nonsteroidal antiandrogen (NSAA).[186][187] It has been used with abiraterone in studies involving Whole genome sequencing that have shown how androgen receptors acquire resistance to them, which determines the use of new therapies against this pathology such as degraders of the protein or of the N-terminal domain of this receptor. This has been seen thanks to the sequencing of circulating tumor DNA in patients.[293]

Alpharadin uses bone targeted Radium-223 isotopes to kill cancer cells by alpha radiation.[294][unreliable medical source?]

PARP inhibitor olaparib is an approved breast/ovarian cancer drug that is undergoing clinical trials.[295] Also in trials for CRPC are : checkpoint inhibitor ipilimumab, CYP17 inhibitor galeterone (TOK-001), and immunotherapy PROSTVAC.[295]

All medications for CRPC block androgen receptor (AR) signaling via direct or indirect targeting of the AR ligand binding domain (LBD). AR belongs to the steroid nuclear receptor family.[296] Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important for disease progression.[297] Molecules that could successfully target alternative domains have emerged.[296] Such therapies could provide an advantage; particularly in treating prostate cancers that are resistant to current therapies.[296]

Evolution

Sequencing techniques, in addition to reflecting the mechanisms of resistance to treatment, through the circulating tumor DNA, distinguish between the evolutionary history of this cancer when it metastasizes and the temporal subclonal dynamics, determining how the tumor is found when it is diagnosed.[293]

Pre-clinical

Arachidonate 5-lipoxygenase has been identified as playing a significant role in the survival of prostate cancer cells.[298][299][300] Medications that target this enzyme are undergoing development.[298][299][300] In particular, arachidonate 5-lipoxygenase inhibitors produce massive, rapid programmed cell death in prostate cancer cells.[298][299][300]

Galectin-3 is another potential target.[301] Aberrant glycan profiles have been described in prostate cancer,[302][303] and studies have found specific links between the galectin signature and prostate cancer.[304][305]

The PIM kinase family is another potential target for selective inhibition. A number of related drugs are under development. It has been suggested the most promising approach may be to co-target this family with other pathways including PI3K.[21]

Cancer models

Scientists have established prostate cancer cell lines to investigate disease progression. LNCaP, PC-3 (PC3), and DU-145 (DU145) are commonly used prostate cancer cell lines.[306] The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express AR, but PC-3 and DU-145 cells express very little or no AR.[citation needed]

The proliferation of LNCaP cells is androgen-dependent but the proliferation of PC-3 and DU-145 cells is androgen-insensitive. Elevation of AR expression is often observed in advanced prostate tumors in patients.[307][308] Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These androgen-independent LNCaP cells have elevated AR expression and express prostate specific antigen upon androgen treatment. Paradoxically, androgens inhibit the proliferation of these androgen-independent prostate cancer cells.[309][310][311]

Diagnosis

One active research area and non-clinically applied investigations involves non-invasive methods of tumor detection.[312] A molecular test that detects the presence of cell-associated PCA3 mRNA in fluid obtained from the prostate and first-void urine sample is under investigation. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. The test result is currently reported as a specimen ratio of PCA3 mRNA to PSA mRNA.[313]

The PCA3 test attempts to help decide whether, in men suspected of having prostate cancer (especially if an initial biopsy fails to explain the elevated serum PSA), a biopsy/rebiopsy is needed. The higher the expression of PCA3 in the sample, the greater the likelihood of a positive biopsy.[314] The CDC's Evaluation of Genomic Applications in Practice and Prevention Working Group discourages clinical use.[315]

See also

References

  1. ^ a b c d "Prostate Cancer Treatment (PDQ) – Health Professional Version". National Cancer Institute. 2014-04-11. from the original on 5 July 2014. Retrieved 1 July 2014.
  2. ^ a b c d e f g h i j "Prostate Cancer Treatment (PDQ) – Patient Version". National Cancer Institute. 2014-04-08. from the original on 5 July 2014. Retrieved 1 July 2014.
  3. ^ a b c d e f g h i j k l "Chapter 5.11". World Cancer Report. World Health Organization. 2014. ISBN 978-9283204299.
  4. ^ a b "SEER Stat Fact Sheets: Prostate Cancer". NCI. from the original on 6 July 2014. Retrieved 18 June 2014.
  5. ^ a b c Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (November 2018). "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries". CA. 68 (6): 394–424. doi:10.3322/caac.21492. PMID 30207593. S2CID 52188256.
  6. ^ "Prostate cancer - Symptoms and causes". Mayo Clinic. Retrieved 2023-02-11.
  7. ^ "What Is Prostate Cancer?". www.cancer.org. Retrieved 2023-02-11.
  8. ^ Luining WI, Cysouw MC, Meijer D, Hendrikse NH, Boellaard R, Vis AN, Oprea-Lager DE (February 2022). "Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer". Cancers. 14 (5): 1169. doi:10.3390/cancers14051169. PMC 8909566. PMID 35267481.
  9. ^ "What Is Prostate Cancer?". www.cancer.org. Retrieved 2022-09-28.
  10. ^ Kalish LA, McDougal WS, McKinlay JB (November 2000). "Family history and the risk of prostate cancer". Urology. 56 (5): 803–806. doi:10.1016/S0090-4295(00)00780-9. PMID 11068306.
  11. ^ Koh KA, Sesso HD, Paffenbarger RS, Lee IM (December 2006). "Dairy products, calcium and prostate cancer risk". British Journal of Cancer. 95 (11): 1582–1585. doi:10.1038/sj.bjc.6603475. PMC 2360740. PMID 17106437.
  12. ^ a b Caini S, Gandini S, Dudas M, Bremer V, Severi E, Gherasim A (August 2014). "Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis". Cancer Epidemiology. 38 (4): 329–338. doi:10.1016/j.canep.2014.06.002. PMID 24986642.
  13. ^ Lee MV, Katabathina VS, Bowerson ML, Mityul MI, Shetty AS, Elsayes KM, et al. (2016). "BRCA-associated Cancers: Role of Imaging in Screening, Diagnosis, and Management". Radiographics. 37 (4): 1005–1023. doi:10.1148/rg.2017160144. PMID 28548905.
  14. ^ "Prostate Cancer Treatment". National Cancer Institute. 6 February 2018. Retrieved 1 March 2018. Controversy exists regarding the value of screening... reported no clear evidence that screening for prostate cancer decreases the risk of death from prostate cancer
  15. ^ a b Catalona WJ (March 2018). "Prostate Cancer Screening". The Medical Clinics of North America. 102 (2): 199–214. doi:10.1016/j.mcna.2017.11.001. PMC 5935113. PMID 29406053.
  16. ^ a b "PSA testing". nhs.uk. 3 January 2015. Retrieved 5 March 2018.
  17. ^ a b "Final Recommendation Statement: Prostate Cancer: Screening". www.uspreventiveservicestaskforce.org. US Preventive Services Task Force (USPSTF). Retrieved 30 August 2018.
  18. ^ Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, Davidson KW, et al. (May 2018). "Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement". JAMA. 319 (18): 1901–1913. doi:10.1001/jama.2018.3710. PMID 29801017.
  19. ^ Cabarkapa S, Perera M, McGrath S, Lawrentschuk N (December 2016). "Prostate cancer screening with prostate-specific antigen: A guide to the guidelines". Prostate International. 4 (4): 125–129. doi:10.1016/j.prnil.2016.09.002. PMC 5153437. PMID 27995110.
  20. ^ a b Stratton J, Godwin M (June 2011). "The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis". Family Practice. 28 (3): 243–252. doi:10.1093/fampra/cmq115. PMID 21273283.
  21. ^ a b c Luszczak S, Kumar C, Sathyadevan VK, Simpson BS, Gately KA, Whitaker HC, Heavey S (January 2020). "PIM kinase inhibition: co-targeted therapeutic approaches in prostate cancer". Signal Transduction and Targeted Therapy. 5 (1): 7. doi:10.1038/s41392-020-0109-y. PMC 6992635. PMID 32296034.
  22. ^ "Chapter 1.1". World Cancer Report. World Health Organization. 2014. ISBN 978-9283204299.
  23. ^ a b Baade PD, Youlden DR, Krnjacki LJ (February 2009). "International epidemiology of prostate cancer: geographical distribution and secular trends". Molecular Nutrition & Food Research. 53 (2): 171–184. doi:10.1002/mnfr.200700511. PMID 19101947.
  24. ^ "Prostate Cancer Signs and Symptoms". www.cancer.org. Retrieved 2023-02-11.
  25. ^ Leslie SW, Soon-Sutton TL, Sajjad H, Siref LE. Prostate Cancer. 2020 Oct 28. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; PMID 29261872.
  26. ^ a b Miller DC, Hafez KS, Stewart A, Montie JE, Wei JT (September 2003). "Prostate carcinoma presentation, diagnosis, and staging: an update form the National Cancer Data Base". Cancer. 98 (6): 1169–1178. doi:10.1002/cncr.11635. hdl:2027.42/34379. PMID 12973840. S2CID 22077473.
  27. ^ "Advanced prostate cancer". Prostate Cancer UK. Retrieved 2023-02-11.
  28. ^ Henninger S, Neusser S, Lorenz C, Bitzer EM (December 2014). "[Prostate cancer in routine healthcare: health-related quality of life after inpatient treatment]". Der Urologe. Ausg. A. 53 (12): 1793–1799. doi:10.1007/s00120-014-3615-0. PMID 25297490.
  29. ^ Bauer RM (2016). "Urinary Dysfunction in Prostate Cancer: Male Slings". In Sandhu JS (ed.). Urinary Dysfunction in Prostate Cancer. Urinary Dysfunction in Prostate Cancer: A Management Guide. Cham: Springer International Publishing. pp. 53–69. doi:10.1007/978-3-319-23817-3_4. ISBN 978-3-319-23817-3. Retrieved 2022-04-28.
  30. ^ "Advanced prostate cancer". Prostate Cancer UK. Retrieved 2023-02-11.
  31. ^ Liu Z, Murphy SF, Huang J, Zhao L, Hall CC, Schaeffer AJ, et al. (July 2020). "A novel immunocompetent model of metastatic prostate cancer-induced bone pain". The Prostate. 80 (10): 782–794. doi:10.1002/pros.23993. PMC 7375026. PMID 32407603.
  32. ^ van der Cruijsen-Koeter IW, Vis AN, Roobol MJ, Wildhagen MF, de Koning HJ, van der Kwast TH, Schröder FH (July 2005). "Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer, section rotterdam". The Journal of Urology. 174 (1): 121–125. doi:10.1097/01.ju.0000162061.40533.0f. PMID 15947595.
  33. ^ a b Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (April 2003). "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults". The New England Journal of Medicine. 348 (17): 1625–1638. doi:10.1056/NEJMoa021423. PMID 12711737. S2CID 22714795.
  34. ^ Maistro S, Xavier CD, Serio PA, Katayama ML, Roela RA, Koike Folgueira MA (2019-05-20). "Cancer driver genes in prostate cancer from young men". Journal of Clinical Oncology. 37 (15_suppl): e16586. doi:10.1200/JCO.2019.37.15_suppl.e16586. ISSN 0732-183X. S2CID 190897312.
  35. ^ Smith CV, Bauer JJ, Connelly RR, Seay T, Kane C, Foley J, et al. (December 2000). "Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database". The Journal of Urology. 164 (6): 1964–1967. doi:10.1016/S0022-5347(05)66929-7. PMID 11061892.
  36. ^ Hankey BF, Feuer EJ, Clegg LX, Hayes RB, Legler JM, Prorok PC, et al. (June 1999). "Cancer surveillance series: interpreting trends in prostate cancer--part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates". Journal of the National Cancer Institute. 91 (12): 1017–1024. doi:10.1093/jnci/91.12.1017. PMID 10379964.
  37. ^ Martin RM, Vatten L, Gunnell D, Romundstad P (March 2010). "Blood pressure and risk of prostate cancer: Cohort Norway (CONOR)". Cancer Causes & Control. 21 (3): 463–472. doi:10.1007/s10552-009-9477-x. PMID 19949849. S2CID 30484327.
  38. ^ Friedenreich CM, Neilson HK, Lynch BM (September 2010). "State of the epidemiological evidence on physical activity and cancer prevention". European Journal of Cancer. 46 (14): 2593–2604. doi:10.1016/j.ejca.2010.07.028. PMID 20843488.
  39. ^ Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ (August 1996). "Prospective study of sex hormone levels and risk of prostate cancer". Journal of the National Cancer Institute. 88 (16): 1118–1126. doi:10.1093/jnci/88.16.1118. PMID 8757191.
  40. ^ "Prostate cancer". Genetics Home Reference. Retrieved 1 May 2020.
  41. ^ a b c d e f g Scher & Eastham 2022, "Epidemiology".
  42. ^ Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. (July 2000). "Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland". The New England Journal of Medicine. 343 (2): 78–85. doi:10.1056/NEJM200007133430201. PMID 10891514.
  43. ^ Hjelmborg JB, Scheike T, Holst K, Skytthe A, Penney KL, Graff RE, et al. (November 2014). "The heritability of prostate cancer in the Nordic Twin Study of Cancer". Cancer Epidemiology, Biomarkers & Prevention. 23 (11): 2303–2310. doi:10.1158/1055-9965.EPI-13-0568. PMC 4221420. PMID 24812039. S2CID 29554506.
  44. ^ Smith JR, Freije D, Carpten JD, Grönberg H, Xu J, Isaacs SD, et al. (November 1996). "Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search". Science. 274 (5291): 1371–1374. Bibcode:1996Sci...274.1371S. doi:10.1126/science.274.5291.1371. PMID 8910276. S2CID 42684655.
  45. ^ Carpten J, Nupponen N, Isaacs S, Sood R, Robbins C, Xu J, et al. (February 2002). "Germline mutations in the ribonuclease L gene in families showing linkage with HPC1". Nature Genetics. 30 (2): 181–184. doi:10.1038/ng823. PMID 11799394. S2CID 2922306.
  46. ^ Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, et al. (January 2012). "Germline mutations in HOXB13 and prostate-cancer risk". The New England Journal of Medicine. 366 (2): 141–149. doi:10.1056/NEJMoa1110000. PMC 3779870. PMID 22236224.
  47. ^ Dupont WD, Breyer JP, Johnson SH, Plummer WD, Smith JR (May 2021). "Prostate cancer risk variants of the HOXB genetic locus". Scientific Reports. 11 (1): 11385. Bibcode:2021NatSR..1111385D. doi:10.1038/s41598-021-89399-7. PMC 8167119. PMID 34059701. S2CID 235269663.
  48. ^ Dupont WD, Breyer JP, Plummer WD, Chang SS, Cookson MS, Smith JA, et al. (March 2020). "8q24 genetic variation and comprehensive haplotypes altering familial risk of prostate cancer". Nature Communications. 11 (1): 1523. Bibcode:2020NatCo..11.1523D. doi:10.1038/s41467-020-15122-1. PMC 7089954. PMID 32251286. S2CID 214606533.
  49. ^ Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, et al. (May 1997). "The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews". The New England Journal of Medicine. 336 (20): 1401–1408. doi:10.1056/NEJM199705153362001. PMID 9145676.
  50. ^ Beuzeboc P, Soulié M, Richaud P, Salomon L, Staerman F, Peyromaure M, et al. (December 2009). "[Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives]". Progres en Urologie (in French). 19 (11): 819–824. doi:10.1016/j.purol.2009.06.002. PMID 19945666.
  51. ^ Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, et al. (April 2013). "Punctuated evolution of prostate cancer genomes". Cell. 153 (3): 666–677. doi:10.1016/j.cell.2013.03.021. PMC 3690918. PMID 23622249.
  52. ^ Gupta N, Patel HD, Taylor J, Borin JF, Jacobsohn K, Kenfield SA, et al. (September 2022). "Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes". Prostate Cancer and Prostatic Diseases. 25 (3): 444–452. doi:10.1097/JU.0000000000002518.04. PMID 35790788. S2CID 248030075.
  53. ^ a b Scher & Eastham 2022, "No Cancer Diagnosis".
  54. ^ "Milk and Health". American College of Cardiology. Retrieved 2021-02-21.
  55. ^ Willett WC, Ludwig DS (February 2020). "Milk and Health". The New England Journal of Medicine. 382 (7): 644–654. doi:10.1056/NEJMra1903547. PMID 32053300. S2CID 211099544.
  56. ^ Sargsyan A, Dubasi HB (July 2021). "Milk Consumption and Prostate Cancer: A Systematic Review". The World Journal of Men's Health. 39 (3): 419–428. doi:10.5534/wjmh.200051. PMC 8255404. PMID 32777868.
  57. ^ López-Plaza B, Bermejo LM, Santurino C, Cavero-Redondo I, Álvarez-Bueno C, Gómez-Candela C (May 2019). "Milk and Dairy Product Consumption and Prostate Cancer Risk and Mortality: An Overview of Systematic Reviews and Meta-analyses". Advances in Nutrition. 10 (suppl_2): S212–S223. doi:10.1093/advances/nmz014. PMC 6518142. PMID 31089741.
  58. ^ Wigle DT, Turner MC, Gomes J, Parent ME (March 2008). "Role of hormonal and other factors in human prostate cancer". Journal of Toxicology and Environmental Health Part B: Critical Reviews. 11 (3–4): 242–259. doi:10.1080/10937400701873548. PMID 18368555. S2CID 24489849.
  59. ^ a b c d e Masko EM, Allott EH, Freedland SJ (May 2013). "The relationship between nutrition and prostate cancer: is more always better?". European Urology. 63 (5): 810–820. doi:10.1016/j.eururo.2012.11.012. PMC 3597758. PMID 23219353.
  60. ^ Thompson AK, Shaw DI, Minihane AM, Williams CM (December 2008). "Trans-fatty acids and cancer: the evidence reviewed". Nutrition Research Reviews. 21 (2): 174–188. doi:10.1017/S0954422408110964. PMID 19087370.
  61. ^ Heinze VM, Actis AB (February 2012). "Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review". International Journal of Food Sciences and Nutrition. 63 (1): 66–78. doi:10.3109/09637486.2011.598849. PMID 21762028. S2CID 21614046.
  62. ^ Datta M, Schwartz GG (2012). "Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: a critical review". The Oncologist. 17 (9): 1171–1179. doi:10.1634/theoncologist.2012-0051. PMC 3448410. PMID 22836449.
  63. ^ Szymanski KM, Wheeler DC, Mucci LA (November 2010). "Fish consumption and prostate cancer risk: a review and meta-analysis". The American Journal of Clinical Nutrition. 92 (5): 1223–1233. doi:10.3945/ajcn.2010.29530. PMID 20844069.
  64. ^ American Dietetic Association (June 2003). "Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets". Journal of the American Dietetic Association. 103 (6): 748–765. doi:10.1053/jada.2003.50142. PMID 12778049.
  65. ^ World Cancer Research Fund; American Institute for Cancer (2007). (PDF). Washington, D.C.: American Institute for Cancer Research. p. 76. ISBN 978-0-9722522-2-5. Archived from the original (PDF) on 2013-05-23.
  66. ^ Rowles JL, Ranard KM, Applegate CC, Jeon S, An R, Erdman JW (September 2018). "Processed and raw tomato consumption and risk of prostate cancer: a systematic review and dose-response meta-analysis". Prostate Cancer and Prostatic Diseases. 21 (3): 319–336. doi:10.1038/s41391-017-0005-x. PMID 29317772. S2CID 3306182.
  67. ^ a b "American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention" (PDF). American Cancer Society. (PDF) from the original on 2012-06-25.
  68. ^ Torti DC, Matheson GO (2004-05-01). "Exercise and prostate cancer". Sports Medicine. 34 (6): 363–369. doi:10.2165/00007256-200434060-00003. PMID 15157121. S2CID 43085964.
  69. ^ Jacobs EJ, Rodriguez C, Mondul AM, Connell CJ, Henley SJ, Calle EE, Thun MJ (July 2005). "A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence". Journal of the National Cancer Institute. 97 (13): 975–980. doi:10.1093/jnci/dji173. PMID 15998950.
  70. ^ Shannon J, Tewoderos S, Garzotto M, Beer TM, Derenick R, Palma A, Farris PE (August 2005). "Statins and prostate cancer risk: a case-control study". American Journal of Epidemiology. 162 (4): 318–325. doi:10.1093/aje/kwi203. PMID 16014776.
  71. ^ Dennis LK, Lynch CF, Torner JC (July 2002). "Epidemiologic association between prostatitis and prostate cancer". Urology. 60 (1): 78–83. doi:10.1016/S0090-4295(02)01637-0. PMID 12100928.
  72. ^ Heidegger I, Borena W, Pichler R (May 2015). "The role of human papilloma virus in urological malignancies". Anticancer Research. 35 (5): 2513–2519. PMID 25964524.
  73. ^ Cai T, Di Vico T, Durante J, Tognarelli A, Bartoletti R (December 2018). "Human papilloma virus and genitourinary cancers: a narrative review". Minerva Urologica e Nefrologica. 70 (6): 579–587. doi:10.23736/S0393-2249.18.03141-7. PMID 30160386. S2CID 52118310.
  74. ^ "Prostate Cancer | Johns Hopkins Brady Urological Institute". www.hopkinsmedicine.org. Retrieved 2022-04-28.
  75. ^ Rider JR, Wilson KM, Sinnott JA, Kelly RS, Mucci LA, Giovannucci EL (December 2016). "Ejaculation Frequency and Risk of Prostate Cancer: Updated Results with an Additional Decade of Follow-up". European Urology. 70 (6): 974–982. doi:10.1016/j.eururo.2016.03.027. PMC 5040619. PMID 27033442.
  76. ^ Aboul-Enein BH, Bernstein J, Ross MW (July 2016). "Evidence for Masturbation and Prostate Cancer Risk: Do We Have a Verdict?". Sexual Medicine Reviews. 4 (3): 229–234. doi:10.1016/j.sxmr.2016.02.006. PMID 27871956.
  77. ^ "A comprehensive cancer control program for BC". Retrieved 2 November 2021.
  78. ^ Aumüller G (1979). Prostate Gland and Seminal Vesicles. Berlin-Heidelberg: Springer-Verlag.
  79. ^ Moore KL, Chubb D (1999). Clinically Oriented Anatomy. Baltimore, Maryland: Lippincott Williams & Wilkins. ISBN 978-0-683-06132-1.
  80. ^ Steive H (1930). "Männliche Genitalorgane". Handbuch der mikroskopischen Anatomie des Menschen. Vol. VII Part 2. Berlin: Springer. pp. 1–399.
  81. ^ Collins MA, Terris MK (2021-10-25). Talavera F, Noble MJ (eds.). "Transurethral Resection of the Prostate: Overview, Treatment & Management, Post-Procedure". Medscape.
  82. ^ McNeal JE (1984). "Anatomy of the prostate and morphogenesis of BPH". Progress in Clinical and Biological Research. 145: 27–53. PMID 6201879.
  83. ^ Muruve MA (2020-06-11). Gest TR (ed.). "Prostate Anatomy: Overview, Gross Anatomy, Microscopic Anatomy". Medscape.
  84. ^ Singh O, Bolla SR (2022). "Anatomy, Abdomen and Pelvis, Prostate". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 31082031. Retrieved 2022-04-28.
  85. ^ Schenkman NS, Manger JP (2020-06-11). Gest TR (ed.). "Male Urethra Anatomy: Overview, Gross Anatomy, Microscopic Anatomy". Medscape.
  86. ^ Pisipati S, Ali A, Mandalapu RS, Haines Iii GK, Singhal P, Reddy BN, et al. (October 2014). "Newer concepts in neural anatomy and neurovascular preservation in robotic radical prostatectomy". Indian Journal of Urology. 30 (4): 399–409. doi:10.4103/0970-1591.142064. PMC 4220380. PMID 25378822.
  87. ^ Oh WK, Hurwitz M, D'Amico AV, Richie JP, Kantoff PW (2003). "Biology of Prostate Cancer". Holland-Frei Cancer Medicine (6th ed.).
  88. ^ Reissigl A, Pointner J, Strasser H, Ennemoser O, Klocker H, Bartsch G (February 1997). "Frequency and clinical significance of transition zone cancer in prostate cancer screening". The Prostate. 30 (2): 130–135. doi:10.1002/(SICI)1097-0045(19970201)30:2<130::AID-PROS8>3.0.CO;2-S. PMID 9051151. S2CID 24142928.
  89. ^ "Androgens: Function, Measurement and Related Disorders". Cleveland Clinic. Retrieved 2022-04-28.
  90. ^ a b "Prostate Cancer: Symptoms, Diagnosis & Treatment". Cleveland Clinic. Retrieved 2022-04-28.
  91. ^ "Prostate Tumor - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2022-04-28.
  92. ^ Zhou M (January 2018). "High-grade prostatic intraepithelial neoplasia, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma of the prostate". Modern Pathology. 31 (S1): S71–S79. doi:10.1038/modpathol.2017.138. PMID 29297491. S2CID 13649812.
  93. ^ Brosman SA, Goluboff ET, Talavera F, Theodorescu D (2021-10-04). Kim ED (ed.). "Precancerous Lesions of the Prostate: Overview, PIN and ASAP Rates, Diagnostic Significance".
  94. ^ "Advanced Prostate Cancer: Symptoms, Diagnosis & Treatment - Urology Care Foundation". www.urologyhealth.org. Retrieved 2022-04-28.
  95. ^ Martin TA, Ye L, Sanders AJ, Lane J, Jiang WG (2013). Cancer Invasion and Metastasis: Molecular and Cellular Perspective. Landes Bioscience.
  96. ^ Leslie SW, Soon-Sutton TL, Sajjad H, Siref LE (2022). "Prostate Cancer". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 29261872. Retrieved 2022-04-28.
  97. ^ . Pathology study images. University of Virginia School of Medicine. Archived from the original on 2011-07-20. Retrieved 2011-04-28. There are many connections between the prostatic venous plexus and the vertebral veins. The veins forming the prostatic plexus do not contain valves and it is thought that straining to urinate causes prostatic venous blood to flow in a reverse direction and enter the vertebral veins carrying malignant cells to the vertebral column.
  98. ^ a b Costello LC, Franklin RB (May 2006). "The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots". Molecular Cancer. 5: 17. doi:10.1186/1476-4598-5-17. PMC 1481516. PMID 16700911.
  99. ^ Vickram S, Rohini K, Srinivasan S, Nancy Veenakumari D, Archana K, Anbarasu K, et al. (February 2021). "Role of Zinc (Zn) in Human Reproduction: A Journey from Initial Spermatogenesis to Childbirth". International Journal of Molecular Sciences. 22 (4): 2188. doi:10.3390/ijms22042188. PMC 7926410. PMID 33671837.
  100. ^ Costello LC, Franklin RB (June 1998). "Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer". The Prostate. 35 (4): 285–296. doi:10.1002/(sici)1097-0045(19980601)35:4<285::aid-pros8>3.0.co;2-f. PMID 9609552. S2CID 21084346.
  101. ^ Franklin RB, Feng P, Milon B, Desouki MM, Singh KK, Kajdacsy-Balla A, et al. (September 2005). "hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer". Molecular Cancer. 4: 32. doi:10.1186/1476-4598-4-32. PMC 1243239. PMID 16153295.
  102. ^ Uzzo RG, Leavis P, Hatch W, Gabai VL, Dulin N, Zvartau N, Kolenko VM (November 2002). "Zinc inhibits nuclear factor-kappa B activation and sensitizes prostate cancer cells to cytotoxic agents". Clinical Cancer Research. 8 (11): 3579–3583. PMID 12429649.
  103. ^ . August 4, 2005. Archived from the original on May 19, 2008.
  104. ^ Sharma A, Yeow WS, Ertel A, Coleman I, Clegg N, Thangavel C, et al. (December 2010). "The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression". The Journal of Clinical Investigation. 120 (12): 4478–4492. doi:10.1172/JCI44239. PMC 2993601. PMID 21099110.
  105. ^ Ruela-de-Sousa RR, Hoekstra E, Hoogland AM, Souza Queiroz KC, Peppelenbosch MP, Stubbs AP, et al. (April 2016). "Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential". European Urology. 69 (4): 710–719. doi:10.1016/j.eururo.2015.06.040. PMID 26159288.
  106. ^ Leav I, Plescia J, Goel HL, Li J, Jiang Z, Cohen RJ, et al. (January 2010). "Cytoprotective mitochondrial chaperone TRAP-1 as a novel molecular target in localized and metastatic prostate cancer". The American Journal of Pathology. 176 (1): 393–401. doi:10.2353/ajpath.2010.090521. PMC 2797899. PMID 19948822.
  107. ^ Zha J, Huang YF (September 2009). "[TGF-beta/Smad in prostate cancer: an update]". Zhonghua Nan Ke Xue = National Journal of Andrology (in Chinese). 15 (9): 840–843. PMID 19947572.
  108. ^ Watanabe S, Miyata Y, Kanda S, Iwata T, Hayashi T, Kanetake H, Sakai H (May 2010). "Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy". Journal of Cancer Research and Clinical Oncology. 136 (5): 787–793. doi:10.1007/s00432-009-0718-x. PMID 19946707. S2CID 34855148.
  109. ^ Senapati S, Rachagani S, Chaudhary K, Johansson SL, Singh RK, Batra SK (March 2010). "Overexpression of macrophage inhibitory cytokine-1 induces metastasis of human prostate cancer cells through the FAK-RhoA signaling pathway". Oncogene. 29 (9): 1293–1302. doi:10.1038/onc.2009.420. PMC 2896817. PMID 19946339.
  110. ^ Narizhneva NV, Tararova ND, Ryabokon P, Shyshynova I, Prokvolit A, Komarov PG, et al. (December 2009). "Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer". Cell Cycle. 8 (24): 4155–4167. doi:10.4161/cc.8.24.10316. PMC 2896895. PMID 19946220.
  111. ^ Yao V, Berkman CE, Choi JK, O'Keefe DS, Bacich DJ (February 2010). "Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid". The Prostate. 70 (3): 305–316. doi:10.1002/pros.21065. PMID 19830782. S2CID 21518526.
  112. ^ a b Alberts AR, Schoots IG, Roobol MJ (June 2015). "Prostate-specific antigen-based prostate cancer screening: Past and future". International Journal of Urology. 22 (6): 524–532. doi:10.1111/iju.12750. PMID 25847604. S2CID 7525080.
  113. ^ a b Rendon RA, Mason RJ, Marzouk K, Finelli A, Saad F, So A, et al. (October 2017). "Canadian Urological Association recommendations on prostate cancer screening and early diagnosis". Canadian Urological Association Journal. 11 (10): 298–309. doi:10.5489/cuaj.4888. PMC 5659858. PMID 29381452.
  114. ^ . USPSTF Draft Prostate Screening Recommendations. Archived from the original on 2 March 2018. Retrieved 2 March 2018.
  115. ^ Mulhem E, Fulbright N, Duncan N (October 2015). "Prostate Cancer Screening". American Family Physician. 92 (8): 683–688. PMID 26554408.
  116. ^ Prostate Cancer Screening 2017-09-07 at the Wayback Machine CDC, updated April 6, 2010
  117. ^ Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P (May 2013). "Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians". Annals of Internal Medicine. 158 (10): 761–769. doi:10.7326/0003-4819-158-10-201305210-00633. PMID 23567643.
  118. ^ Basch E, Oliver TK, Vickers A, Thompson I, Kantoff P, Parnes H, et al. (August 2012). "Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion". Journal of Clinical Oncology. 30 (24): 3020–3025. doi:10.1200/JCO.2012.43.3441. PMC 3776923. PMID 22802323.
  119. ^ Carter HB (September 2013). "American Urological Association (AUA) guideline on prostate cancer detection: process and rationale". BJU International. 112 (5): 543–547. doi:10.1111/bju.12318. PMID 23924423. S2CID 19703425.
  120. ^ . American Urological Association. 2013. Archived from the original on 7 May 2013. Retrieved 10 May 2013.
  121. ^ "Cancer Screening Guidelines | Detecting Cancer Early". from the original on 2011-06-13. Retrieved 2011-06-16. American Cancer Society American Cancer Society Guidelines for the early detection of cancer Cited: September 2011
  122. ^ "Prostate Cancer and the Digital Rectal Exam". WebMD. Retrieved 2022-04-28.
  123. ^ "Cystoscopy: Purpose, Procedure, and Preparation". Healthline. 2015-10-19. Retrieved 2022-04-28.
  124. ^ Scher & Eastham 2022, "Prostate Biopsy".
  125. ^ El Shafei AR, Jones JS (2021-10-04). Kim ED (ed.). "Prostate Biopsy: Practice Essentials, Background, Indications and Contraindications". Medscape.
  126. ^ Drost FH, Osses D, Nieboer D, Bangma CH, Steyerberg EW, Roobol MJ, Schoots IG (January 2020). "Prostate Magnetic Resonance Imaging, with or Without Magnetic Resonance Imaging-targeted Biopsy, and Systematic Biopsy for Detecting Prostate Cancer: A Cochrane Systematic Review and Meta-analysis". European Urology. 77 (1): 78–94. doi:10.1016/j.eururo.2019.06.023. PMID 31326219. S2CID 198131275.
  127. ^ "Transrectal Ultrasonography - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2022-04-28.
  128. ^ Ebeid AI, Elshamy AS (2018-09-01). "Hypoechoic versus hypervascular lesion in the diagnosis of prostatic carcinoma". African Journal of Urology. 24 (3): 169–174. doi:10.1016/j.afju.2018.01.004. ISSN 1110-5704. S2CID 81718491.
  129. ^ Yaghi MD, Kehinde EO (2015). "Oral antibiotics in trans-rectal prostate biopsy and its efficacy to reduce infectious complications: Systematic review". Urology Annals. 7 (4): 417–427. doi:10.4103/0974-7796.164860. PMC 4660689. PMID 26538868.
  130. ^ Zani EL, Clark OA, Rodrigues Netto N (May 2011). "Antibiotic prophylaxis for transrectal prostate biopsy". The Cochrane Database of Systematic Reviews (5): CD006576. doi:10.1002/14651858.CD006576.pub2. PMID 21563156.
  131. ^ Essink-Bot ML, de Koning HJ, Nijs HG, Kirkels WJ, van der Maas PJ, Schröder FH (June 1998). "Short-term effects of population-based screening for prostate cancer on health-related quality of life". Journal of the National Cancer Institute. 90 (12): 925–931. doi:10.1093/jnci/90.12.925. PMID 9637143.
  132. ^ a b c d Scher & Eastham 2022, "Pathology".
  133. ^ Chuang AY, DeMarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI (August 2007). "Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma". The American Journal of Surgical Pathology. 31 (8): 1246–1255. doi:10.1097/PAS.0b013e31802f5d33. PMID 17667550. S2CID 11535862.
  134. ^ References for pie chart are located in table in the article Histopathologic diagnosis of prostate cancer: Incidences[spelling?] generally include cases where the pattern is found admixed with usual acinar adenocarcinoma.
  135. ^ a b "Prostate Cancer Staging". American Cancer Society. 8 October 2021. Retrieved 14 May 2023.
  136. ^ a b c Scher & Eastham 2022, "Table 87-1 TNM Classification".
  137. ^ "Prostate cancer: diagnosis and management. NICE guideline [NG131]". National Institute for Health and Care Excellence (NICE). Retrieved 2022-10-03.
  138. ^ "EAU Guidelines on Prostate Cancer - DIAGNOSTIC EVALUATION". Uroweb. European Association of Urology. March 2023. Retrieved 15 May 2023.
  139. ^ National Comprehensive Cancer Network – Prostate (2012). "NCCN Clinical Practice Guidelines in Oncology". nccn.org. from the original on 9 November 2012. Retrieved 15 November 2012.
  140. ^ Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, Cookson MS, et al. (June 2007). "Guideline for the management of clinically localized prostate cancer: 2007 update". The Journal of Urology. 177 (6): 2106–2131. doi:10.1016/j.juro.2007.03.003. PMID 17509297.
  141. ^ American Society of Clinical Oncology (April 2013). (PDF). The Journal of the Oklahoma State Medical Association. 106 (4): 150–151. PMID 23795527. Archived from the original (PDF) on 2012-07-31.
  142. ^ Makarov DV, Desai RA, Yu JB, Sharma R, Abraham N, Albertsen PC, et al. (January 2012). "The population level prevalence and correlates of appropriate and inappropriate imaging to stage incident prostate cancer in the medicare population". The Journal of Urology. 187 (1): 97–102. doi:10.1016/j.juro.2011.09.042. PMID 22088337.
  143. ^ Macedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L, Goncalves F (March 2017). "Bone Metastases: An Overview". Oncology Reviews. 11 (1): 321. doi:10.4081/oncol.2017.321. PMC 5444408. PMID 28584570.
  144. ^ Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. (April 2020). "Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study". Lancet. 395 (10231): 1208–1216. doi:10.1016/S0140-6736(20)30314-7. PMID 32209449. S2CID 214609500.
  145. ^ "FDA approves novel PSMA-PET imaging product for prostate cancer". Urology Times. Retrieved 2023-01-04.
  146. ^ "PSMA Radiopharmaceutical Effective against Prostate Cancer". National Cancer Institute. National Institutes of Health. 29 June 2021.
  147. ^ Fallahi, Babak; Khademi, Niloufar; Karamzade-Ziarati, Najme; Fard-Esfahani, Armaghan; Emami-Ardekani, Alireza; Farzanefar, Saeed; Eftekhari, Mohammad; Beiki, Davood (February 2021). "99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer". Clinical Nuclear Medicine. 46 (2): e68–e74. doi:10.1097/RLU.0000000000003410. ISSN 1536-0229. PMID 33234922. S2CID 227168658.
  148. ^ Harsini, Sara; Fallahi, Babak; Karamzade Ziarati, Najme; Razi, Ali; Amini, Erfan; Emami-Ardekani, Alireza; Fard-Esfahani, Armaghan; Kardoust Parizi, Mehdi; Farzanehfar, Saeed; Beiki, Davood (2021). "A Prospective Study on [68Ga]-PSMA PET/CT Imaging in Newly Diagnosed Intermediate- and High-Risk Prostate Cancer". Asia Oceania Journal of Nuclear Medicine & Biology. 9 (2): 101–110. doi:10.22038/AOJNMB.2020.52375.1358. ISSN 2322-5718. PMC 8255520. PMID 34250139.
  149. ^ a b c d Filson CP, Marks LS, Litwin MS (8 May 2015). "Expectant management for men with early stage prostate cancer". CA. 65 (4): 265–282. doi:10.3322/caac.21278. PMID 25958817. S2CID 36057004.
  150. ^ Jayadevappa R, Chhatre S, Wong YN, Wittink MN, Cook R, Morales KH, et al. (May 2017). "Comparative effectiveness of prostate cancer treatments for patient-centered outcomes: A systematic review and meta-analysis (PRISMA Compliant)". Medicine. 96 (18): e6790. doi:10.1097/MD.0000000000006790. PMC 5419922. PMID 28471976.
  151. ^ Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, et al. (September 2009). "Outcomes of localized prostate cancer following conservative management". JAMA. 302 (11): 1202–1209. doi:10.1001/jama.2009.1348. PMC 2822438. PMID 19755699.
  152. ^ Mongiat-Artus P, Peyromaure M, Richaud P, Droz JP, Rainfray M, Jeandel C, et al. (December 2009). "[Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French association of urology]". Progres en Urologie (in French). 19 (11): 810–817. doi:10.1016/j.purol.2009.02.008. PMID 19945664.
  153. ^ Picard JC, Golshayan AR, Marshall DT, Opfermann KJ, Keane TE (November 2009). "The multi-disciplinary management of high-risk prostate cancer". Urologic Oncology. 30 (1): 3–15. doi:10.1016/j.urolonc.2009.09.002. PMID 19945310.
  154. ^ a b Mohan R, Schellhammer PF (August 2011). "Treatment options for localized prostate cancer". American Family Physician. 84 (4): 413–420. PMID 21842788.
  155. ^ Rawla P (April 2019). "Epidemiology of Prostate Cancer". World Journal of Oncology. 10 (2): 63–89. doi:10.14740/wjon1191. PMC 6497009. PMID 31068988.
  156. ^ Fitzpatrick JM (March 2008). "Management of localized prostate cancer in senior adults: the crucial role of comorbidity". BJU International. 101 Suppl 2 (Suppl 2): 16–22. doi:10.1111/j.1464-410X.2007.07487.x. PMID 18307688. S2CID 205538470.
  157. ^ "Evidence-Based Cancer Guidelines, Oncology Drug Compendium, Oncology Continuing Medical Education". NCCN. Retrieved 2011-08-29.
  158. ^ Cooper GM (2000). "The Development and Causes of Cancer". The Cell: A Molecular Approach (2nd ed.).
  159. ^ . Cancer Care Ontario. Archived from the original on 2020-04-10.
  160. ^ Ellis SD, Hwang S, Morrow E, Kimminau KS, Goonan K, Petty L, et al. (May 2021). "Perceived barriers to the adoption of active surveillance in low-risk prostate cancer: a qualitative analysis of community and academic urologists". BMC Cancer. 21 (1): 649. doi:10.1186/s12885-021-08386-3. PMC 8165996. PMID 34058998.
  161. ^ "Cancer". www.who.int. Retrieved 2022-04-28.
  162. ^ . Cancer.gov. 2011-04-19. Archived from the original on 2011-05-03. Retrieved 2011-08-29.
  163. ^ a b c d Vernooij RW, Lancee M, Cleves A, Dahm P, Bangma CH, Aben KK (June 2020). "Radical prostatectomy versus deferred treatment for localised prostate cancer". The Cochrane Database of Systematic Reviews. 2020 (6): CD006590. doi:10.1002/14651858.CD006590.pub3. PMC 7270852. PMID 32495338.
  164. ^ Sartor O, de Bono JS (February 2018). "Metastatic Prostate Cancer". The New England Journal of Medicine. 378 (7): 645–657. doi:10.1056/NEJMra1701695. PMID 29412780.
  165. ^ "Prostate cancer - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2022-04-28.
  166. ^ Dhondt B, De Bleser E, Claeys T, Buelens S, Lumen N, Vandesompele J, et al. (December 2019). "Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time". World Journal of Urology. 37 (12): 2557–2564. doi:10.1007/s00345-018-2609-8. PMID 30578441. S2CID 58594673.
  167. ^ "Hormone Therapy for Breast Cancer | Breast Cancer Treatment". www.cancer.org. Retrieved 2022-04-28.
  168. ^ Hammerstrom AE, Cauley DH, Atkinson BJ, Sharma P (August 2011). "Cancer immunotherapy: sipuleucel-T and beyond". Pharmacotherapy. 31 (8): 813–828. doi:10.1592/phco.31.8.813. PMC 4159742. PMID 21923608.
  169. ^ "Prostate Cancer: Radical Prostatectomy". WebMD. Retrieved 10 May 2020.
  170. ^ "Radical Prostatectomy for Prostate Cancer | Memorial Sloan Kettering Cancer Center". www.mskcc.org. Retrieved 2022-05-25.
  171. ^ Mouraviev V, Evans B, Polascik TJ (2006). "Salvage prostate cryoablation after primary interstitial brachytherapy failure: a feasible approach". Prostate Cancer and Prostatic Diseases. 9 (1): 99–101. doi:10.1038/sj.pcan.4500853. PMID 16314889.
  172. ^ Wallis CJ, Mahar AL, Choo R, Herschorn S, Kodama RT, Shah PS, et al. (March 2016). "Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis". BMJ. 352: i851. doi:10.1136/bmj.i851. PMC 4775870. PMID 26936410.
  173. ^ Wallis CJ, Glaser A, Hu JC, Huland H, Lawrentschuk N, Moon D, et al. (January 2018). "Survival and Complications Following Surgery and Radiation for Localized Prostate Cancer: An International Collaborative Review" (PDF). European Urology. 73 (1): 11–20. doi:10.1016/j.eururo.2017.05.055. PMID 28610779.
  174. ^ Hong H, Zhang Y, Sun J, Cai W (June 2010). "Positron emission tomography imaging of prostate cancer". Amino Acids. 39 (1): 11–27. doi:10.1007/s00726-009-0394-9. PMC 2883014. PMID 19946787.
  175. ^ Peyromaure M, Valéri A, Rebillard X, Beuzeboc P, Richaud P, Soulié M, Salomon L (December 2009). "[Characteristics of prostate cancer in men less than 50-year-old]". Progres en Urologie (in French). 19 (11): 803–809. doi:10.1016/j.purol.2009.04.010. PMID 19945663.
  176. ^ "Castrate-resistant prostate cancer: In NCI Dictionary of Cancer Terms". National Cancer Institute, US National Institutes of Health. 2019. Retrieved 17 September 2019.
  177. ^ "Treatments for castrate-resistant prostate cancer". Canadian Cancer Society. 2019. Retrieved 17 September 2019.
  178. ^ Tran K, McGill S. Treatment Sequences of Androgen Receptor–Targeted Agents for Prostate Cancer [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2021 March Available from: https://www.ncbi.nlm.nih.gov/books/NBK571920/
  179. ^ Seruga B, Ocana A, Tannock IF (January 2011). "Drug resistance in metastatic castration-resistant prostate cancer". Nature Reviews. Clinical Oncology. 8 (1): 12–23. doi:10.1038/nrclinonc.2010.136. PMID 20859283. S2CID 24512148.
  180. ^ Clarke NW (2005). (PDF). Archived from the original (PDF) on 2012-07-12.
  181. ^ . National Institute for Health and Clinical Excellence. 2010-12-10. Archived from the original on 2012-02-02. Retrieved 2011-07-04.
  182. ^ de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. (October 2010). "Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial". Lancet. 376 (9747): 1147–1154. doi:10.1016/S0140-6736(10)61389-X. PMID 20888992. S2CID 4791847.
  183. ^ . March 2010. Archived from the original on 15 June 2010. Retrieved 10 May 2010.
  184. ^ Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. (July 2010). "Sipuleucel-T immunotherapy for castration-resistant prostate cancer". The New England Journal of Medicine. 363 (5): 411–422. doi:10.1056/NEJMoa1001294. PMID 20818862. S2CID 12168204.
  185. ^ "FDA approves Zytiga for late-stage prostate cancer". U.S. Food and Drug Administration. 2011-04-28. from the original on 2013-09-22.
  186. ^ a b c (Press release). Food and Drug Administration. 2012-08-31. Archived from the original on 2013-10-02.
  187. ^ a b c Azvolinsky A (September 4, 2012). "FDA Approves Enzalutamide (Xtandi) for Late-Stage Prostate Cancer". CancerNetwork. from the original on September 13, 2012.
  188. ^ Qin J, Liu X, Laffin B, Chen X, Choy G, Jeter CR, et al. (May 2012). "The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration". Cell Stem Cell. 10 (5): 556–569. doi:10.1016/j.stem.2012.03.009. PMC 3348510. PMID 22560078.
  189. ^ Maitland NJ, Collins AT (June 2008). "Prostate cancer stem cells: a new target for therapy". Journal of Clinical Oncology. 26 (17): 2862–2870. doi:10.1200/JCO.2007.15.1472. PMID 18539965.
  190. ^ Attard G, Richards J, de Bono JS (April 2011). "New strategies in metastatic prostate cancer: targeting the androgen receptor signaling pathway". Clinical Cancer Research. 17 (7): 1649–1657. doi:10.1158/1078-0432.CCR-10-0567. PMC 3513706. PMID 21372223.
  191. ^ Rane JK, Pellacani D, Maitland NJ (October 2012). "Advanced prostate cancer--a case for adjuvant differentiation therapy". Nature Reviews. Urology. 9 (10): 595–602. doi:10.1038/nrurol.2012.157. PMID 22890299. S2CID 43634798.
  192. ^ a b Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, et al. (Cochrane Urology Group) (December 2020). "Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis". The Cochrane Database of Systematic Reviews. 2020 (12): CD013020. doi:10.1002/14651858.CD013020.pub2. PMC 8095056. PMID 33270906.
  193. ^ "Radical prostatectomy: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2022-04-28.
  194. ^ Khera M, Miles BJ, Cornell RJ, Colen JS (2021-10-16). Schwartz BF (ed.). "Simple Prostatectomy: Overview, Preparation, Technique". Medscape.
  195. ^ a b "Surgery for Prostate Cancer". www.cancer.org. Retrieved 2020-03-30.
  196. ^ a b Ilic D, Evans SM, Allan CA, Jung JH, Murphy D, Frydenberg M (September 2017). "Laparoscopic and robotic-assisted versus open radical prostatectomy for the treatment of localised prostate cancer". The Cochrane Database of Systematic Reviews. 2017 (9): CD009625. doi:10.1002/14651858.cd009625.pub2. PMC 6486168. PMID 28895658.
  197. ^ a b Tan N, Margolis DJ, McClure TD, Thomas A, Finley DS, Reiter RE, et al. (August 2012). "Radical prostatectomy: value of prostate MRI in surgical planning". Abdominal Imaging. 37 (4): 664–674. doi:10.1007/s00261-011-9805-y. PMID 21993567. S2CID 20471235.
  198. ^ Scheltema MJ, Tay KJ, Postema AW, de Bruin DM, Feller J, Futterer JJ, et al. (May 2017). "Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project". World Journal of Urology. 35 (5): 695–701. doi:10.1007/s00345-016-1932-1. OCLC 1188365278. PMC 5397427. PMID 27637908.
  199. ^ Wang T, Zhou J, Tian S, Wang Y, Patel P, Jani AB, et al. (March 2020). "A planning study of focal dose escalations to multiparametric MRI-defined dominant intraprostatic lesions in prostate proton radiation therapy". The British Journal of Radiology. 93 (1107): 20190845. doi:10.1259/bjr.20190845. PMC 7066949. PMID 31904261.
  200. ^ Heavey S, Haider A, Sridhar A, Pye H, Shaw G, Freeman A, Whitaker H (October 2019). "Use of Magnetic Resonance Imaging and Biopsy Data to Guide Sampling Procedures for Prostate Cancer Biobanking". Journal of Visualized Experiments (152). doi:10.3791/60216. PMID 31657791.
  201. ^ Heavey S, Costa H, Pye H, Burt EC, Jenkinson S, Lewis GR, et al. (May 2019). "PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens". The Prostate. 79 (7): 768–777. doi:10.1002/pros.23782. PMC 6618051. PMID 30807665.
  202. ^ . Continence Foundation of Australia. Archived from the original on 2020-04-10.
  203. ^ "Prostate Cancer and Urinary Incontinence". WebMD. Retrieved 2022-04-28.
  204. ^ "Incontinence After Prostate Cancer Surgery". Cleveland Clinic. Retrieved 2022-04-28.
  205. ^ Singla N, Singla AK (March 2014). "Post-prostatectomy incontinence: Etiology, evaluation, and management". Turkish Journal of Urology. 40 (1): 1–8. doi:10.5152/tud.2014.222014. PMC 4548645. PMID 26328137.
  206. ^ Sajadi KP, Terris MK (2021-11-29). Talavera F (ed.). "Artificial Urinary Sphincter Placement: Practice Essentials, History of the Procedure, Problem". Medscape.
  207. ^ (PDF). European Association of Urology. 2018. Archived from the original (PDF) on 2020-02-08. Retrieved 2020-04-01.
  208. ^ "Erectile Dysfunction After Prostate Cancer". www.hopkinsmedicine.org. 19 November 2019. Retrieved 2020-04-01.
  209. ^ Parahoo K, McDonough S, McCaughan E, Noyes J, Semple C, Halstead EJ, et al. (December 2013). Parahoo K (ed.). "Psychosocial interventions for men with prostate cancer". The Cochrane Database of Systematic Reviews (12): CD008529. doi:10.1002/14651858.CD008529.pub3. PMID 24368598.
  210. ^ Vartolomei L, Shariat SF, Vartolomei MD (September 2018). "Psychotherapeutic Interventions Targeting Prostate Cancer Patients: A Systematic Review of the Literature". European Urology Oncology. 1 (4): 283–291. doi:10.1016/j.euo.2018.04.011. PMID 31100249. S2CID 81502256.
  211. ^ Nnate DA, Anyachukwu CC, Igwe SE, Abaraogu UO (October 2021). "Mindfulness-based interventions for psychological wellbeing and quality of life in men with prostate cancer: A systematic review and meta-analysis". Psycho-Oncology. 30 (10): 1680–1690. doi:10.1002/pon.5749. PMID 34139035. S2CID 235470939.
  212. ^ . seer.cancer.gov. Archived from the original on 18 March 2017. Retrieved 11 April 2017.
  213. ^ Wakai K (February 2005). "[Descriptive epidemiology of prostate cancer in Japan and Western countries]". Nihon Rinsho. Japanese Journal of Clinical Medicine (in Japanese). 63 (2): 207–212. PMID 15714967.
  214. ^ Jaubert de Beaujeu M, Chavrier Y (January 1976). "[Deformations of the anterior thoracic wall (author's transl)]". Annales de Chirurgie Thoracique et Cardio-Vasculaire (in French). 15 (1): 1–6. PMID 1259345.
  215. ^ Hsing AW, Tsao L, Devesa SS (January 2000). "International trends and patterns of prostate cancer incidence and mortality". International Journal of Cancer. 85 (1): 60–67. doi:10.1002/(SICI)1097-0215(20000101)85:1<60::AID-IJC11>3.0.CO;2-B. PMID 10585584. S2CID 21911559.
  216. ^ Osegbe DN (April 1997). "Prostate cancer in Nigerians: facts and nonfacts". The Journal of Urology. 157 (4): 1340–1343. doi:10.1016/S0022-5347(01)64966-8. PMID 9120935.
  217. ^ Bello JO (May 2017). "Predictors of survival outcomes in native sub Saharan black men newly diagnosed with metastatic prostate cancer". BMC Urology. 17 (1): 39. doi:10.1186/s12894-017-0228-0. PMC 5450414. PMID 28558685.
  218. ^ Nelson WG, Antonarakis ES, Carter HB, De Marzo AM, DeWeese TL (2020-01-01). "81 - Prostate Cancer". In Niederhuber JE, Armitage JO, Kastan MB, Doroshow JH (eds.). Abeloff's Clinical Oncology (Sixth ed.). Philadelphia: Elsevier. pp. 1401–1432.e7. ISBN 978-0-323-47674-4.
  219. ^ Di Blasio CJ, Rhee AC, Cho D, Scardino PT, Kattan MW (October 2003). "Predicting clinical end points: treatment nomograms in prostate cancer". Seminars in Oncology. 30 (5): 567–586. doi:10.1016/S0093-7754(03)00351-8. PMID 14571407.
  220. ^ Løvf M, Zhao S, Axcrona U, Johannessen B, Bakken AC, Carm KT, et al. (March 2019). "Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity". European Urology. 75 (3): 498–505. doi:10.1016/j.eururo.2018.08.009. PMID 30181068. S2CID 52156954.
  221. ^ prostate.predict.nhs.uk
  222. ^ Devos G, Joniau S (July 2020). "PREDICT Prostate, a useful tool in men with low- and intermediate-risk prostate cancer who are hesitant between conservative management and active treatment". BMC Medicine. 18 (1): 213. doi:10.1186/s12916-020-01681-z. PMC 7364577. PMID 32669105. S2CID 220544109.
  223. ^ Thurtle D, Bratt O, Stattin P, Pharoah P, Gnanapragasam V (June 2020). "Comparative performance and external validation of the multivariable PREDICT Prostate tool for non-metastatic prostate cancer: a study in 69,206 men from Prostate Cancer data Base Sweden (PCBaSe)". BMC Medicine. 18 (1): 139. doi:10.1186/s12916-020-01606-w. PMC 7296776. PMID 32539712. S2CID 219691220.
  224. ^ Thurtle DR, Greenberg DC, Lee LS, Huang HH, Pharoah PD, Gnanapragasam VJ (March 2019). "Individual prognosis at diagnosis in nonmetastatic prostate cancer: Development and external validation of the PREDICT Prostate multivariable model". PLOS Medicine. 16 (3): e1002758. doi:10.1371/journal.pmed.1002758. PMC 6413892. PMID 30860997.
  225. ^ Thurtle DR, Jenkins V, Pharoah PD, Gnanapragasam VJ (October 2019). "Understanding of prognosis in non-metastatic prostate cancer: a randomised comparative study of clinician estimates measured against the PREDICT prostate prognostic model". British Journal of Cancer. 121 (8): 715–718. doi:10.1038/s41416-019-0569-4. PMC 6889281. PMID 31523057. S2CID 202573988.
  226. ^ Thurtle D, Jenkins V, Freeman A, Pearson M, Recchia G, Tamer P, et al. (November 2021). "Clinical Impact of the Predict Prostate Risk Communication Tool in Men Newly Diagnosed with Nonmetastatic Prostate Cancer: A Multicentre Randomised Controlled Trial" (PDF). European Urology. 80 (5): 661–669. doi:10.1016/j.eururo.2021.08.001. PMID 34493413. S2CID 237440530.
  227. ^ "Endorsed resource – Predict Prostate | Prostate cancer: Diagnosis and management | Guidance | NICE".
  228. ^ Hellerstedt BA, Pienta KJ (2002). "The current state of hormonal therapy for prostate cancer". CA. 52 (3): 154–179. doi:10.3322/canjclin.52.3.154. PMID 12018929. S2CID 25311034.
  229. ^ Feldman BJ, Feldman D (October 2001). "The development of androgen-independent prostate cancer". Nature Reviews. Cancer. 1 (1): 34–45. doi:10.1038/35094009. PMID 11900250. S2CID 205020623.
  230. ^ Hernandez DJ, Nielsen ME, Han M, Partin AW (November 2007). "Contemporary evaluation of the D'amico risk classification of prostate cancer". Urology. 70 (5): 931–935. doi:10.1016/j.urology.2007.08.055. PMID 18068450.
  231. ^ Eifler JB, Feng Z, Lin BM, Partin MT, Humphreys EB, Han M, et al. (January 2013). "An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011". BJU International. 111 (1): 22–29. doi:10.1111/j.1464-410X.2012.11324.x. PMC 3876476. PMID 22834909.
  232. ^ "Prostate Cancer Nomograms | Memorial Sloan Kettering Cancer Center". www.mskcc.org. Retrieved 2022-04-28.
  233. ^ . 2006-09-27. Archived from the original on 2006-09-27. Retrieved 2020-08-08.
  234. ^ Cooperberg MR, Pasta DJ, Elkin EP, Litwin MS, Latini DM, Du Chane J, Carroll PR (June 2005). "The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy". The Journal of Urology. 173 (6): 1938–1942. doi:10.1097/01.ju.0000158155.33890.e7. PMC 2948569. PMID 15879786.
  235. ^ Cooperberg MR, Freedland SJ, Pasta DJ, Elkin EP, Presti JC, Amling CL, et al. (November 2006). "Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy". Cancer. 107 (10): 2384–2391. doi:10.1002/cncr.22262. PMID 17039503. S2CID 17420454.
  236. ^ May M, Knoll N, Siegsmund M, Fahlenkamp D, Vogler H, Hoschke B, Gralla O (November 2007). "Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients". The Journal of Urology. 178 (5): 1957–62, discussion 1962. doi:10.1016/j.juro.2007.07.043. PMID 17868719.
  237. ^ Zhao KH, Hernandez DJ, Han M, Humphreys EB, Mangold LA, Partin AW (August 2008). "External validation of University of California, San Francisco, Cancer of the Prostate Risk Assessment score". Urology. 72 (2): 396–400. doi:10.1016/j.urology.2007.11.165. PMID 18372031.
  238. ^ Cooperberg MR, Broering JM, Carroll PR (June 2009). "Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis". Journal of the National Cancer Institute. 101 (12): 878–887. doi:10.1093/jnci/djp122. PMC 2697208. PMID 19509351.
  239. ^ "New guidance regarding the diagnosis and risk stratification of patients with prostate cancer". BJU International. 129 (3): 304–305. March 2022. doi:10.1111/bju.15703. PMID 35297163. S2CID 247475696.
  240. ^ Gnanapragasam VJ, Lophatananon A, Wright KA, Muir KR, Gavin A, Greenberg DC (August 2016). "Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study". PLOS Medicine. 13 (8): e1002063. doi:10.1371/journal.pmed.1002063. PMC 4970710. PMID 27483464.
  241. ^ Gnanapragasam VJ, Bratt O, Muir K, Lee LS, Huang HH, Stattin P, Lophatananon A (February 2018). "The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study". BMC Medicine. 16 (1): 31. doi:10.1186/s12916-018-1019-5. PMC 5831573. PMID 
May 15, 2023
prostate, cancer, cancer, prostate, second, most, common, cancerous, tumor, worldwide, fifth, leading, cause, cancer, related, mortality, among, prostate, gland, male, reproductive, system, that, surrounds, urethra, just, below, bladder, located, hypogastric, . Cancer of the prostate 6 7 is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer related mortality among men 8 The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder It is located in the hypogastric region of the abdomen To give an idea of where it is located the bladder is superior to the prostate gland as shown in the image 9 The rectum is posterior in perspective to the prostate gland and the ischial tuberosity of the pelvic bone is inferior Most prostate cancers are slow growing Cancerous cells may spread to other areas of the body particularly the bones and lymph nodes It may initially cause no symptoms In later stages symptoms include pain or difficulty urinating blood in the urine or pain in the pelvis or back Benign prostatic hyperplasia may produce similar symptoms Other late symptoms include fatigue due to low levels of red blood cells Prostate cancerOther namesCarcinoma of the prostatePosition of the prostateSpecialtyOncology urologySymptomsNone difficulty urinating blood in the urine pain in the pelvis back or when urinating 1 2 Usual onsetAge gt 50 3 Risk factorsOlder age family history race 3 Diagnostic methodTissue biopsy medical imaging 2 Differential diagnosisBenign prostatic hyperplasia 1 TreatmentActive surveillance surgery radiation therapy hormone therapy chemotherapy 2 Prognosisfive year survival rate 97 1 US 4 Frequency1 2 million new cases 2018 5 Deaths359 000 2018 5 Factors that increase the risk of prostate cancer include older age family history and race 3 10 About 99 of cases occur after age 50 3 A first degree relative with the disease increases the risk two to three fold 3 Other factors include a diet high in processed meat and red meat 3 while the risk from a high intake of milk products is inconclusive 11 An association with gonorrhea has been found although no reason for this relationship has been identified 12 An increased risk is associated with the BRCAmutations 13 Diagnosis is by biopsy 2 Medical imaging may be done to assess whether metastasis is present 2 Prostate cancer screening including prostate specific antigen PSA testing increases cancer detection but whether it improves outcomes is controversial 3 14 15 16 Informed decision making is recommended for those 55 to 69 years old 17 18 Testing if carried out is more appropriate for those with a longer life expectancy 19 Although 5a reductase inhibitors appear to decrease low grade cancer risk they do not affect high grade cancer risk and are not recommended for prevention 3 Vitamin or mineral supplementation does not appear to affect risk 3 20 Many cases are managed with active surveillance or watchful waiting 2 Other treatments may include a combination of surgery radiation therapy hormone therapy or chemotherapy 2 Tumors limited to the prostate may be curable 1 Pain medications bisphosphonates and targeted therapy 21 among others may be useful 2 Outcomes depend on age health status and how aggressive and extensive the cancer is 2 Most men with prostate cancer do not die from it 2 The United States five year survival rate is 97 1 4 Globally it is the second most common cancer It is the fifth leading cause of cancer related death in men 22 In 2018 it was diagnosed in 1 2 million and caused 359 000 deaths 5 It was the most common cancer in males in 84 countries 3 occurring more commonly in the developed world 23 Rates have been increasing in the developing world 23 Detection increased significantly in the 1980s and 1990s in many areas due to increased PSA testing 3 One study reported prostate cancer in 30 to 70 of Russian and Japanese men over age 60 who had died of unrelated causes 1 Contents 1 Signs and symptoms 2 Risk factors 2 1 Genetics 2 2 Lifestyle 2 3 Medication exposure 2 4 Infection 2 5 Environment 2 6 Sex 3 Pathophysiology 4 Screening 5 Diagnosis 5 1 Staging 6 Prevention 7 Management 7 1 Surveillance 7 2 Active treatment 7 2 1 Nonsurgical treatment 7 2 2 Surgery 7 2 3 Uses of MRI 7 2 4 Complications 7 3 Psychological 8 Prognosis 8 1 Classification systems 8 2 Life expectancy 9 Epidemiology 9 1 United States 9 2 Canada 9 3 Europe 10 History 11 Society and culture 12 Research 12 1 Castration resistant prostate cancer 12 1 1 Evolution 12 2 Pre clinical 12 3 Cancer models 12 4 Diagnosis 13 See also 14 References 14 1 Works cited 15 External linksSigns and symptoms Edit A diagram of prostate cancer pressing on the urethra which can cause symptoms Prostate cancer Early prostate cancer usually has no clear symptoms 24 When they do appear they are often similar to those of benign prostatic hyperplasia These include frequent urination nocturia increased urination at night difficulty starting and maintaining a steady stream of urine hematuria blood in the urine dysuria painful urination as well as fatigue due to anemia and bone pain 25 One study found that about a third of diagnosed patients had one or more such symptoms 26 27 Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra 28 29 Changes within the gland directly affect urinary function Because the vas deferens deposits seminal fluid into the prostatic urethra and secretions from the prostate are included in semen content prostate cancer may also cause problems with sexual function and performance such as difficulty achieving erection or painful ejaculation 26 Metastatic prostate cancer can cause additional symptoms 30 The most common symptom is bone pain often in the vertebrae bones of the spine pelvis or ribs 31 Spread of cancer into other bones such as the femur is usually to the part of the bone nearer to the prostate Prostate cancer in the spine can compress the spinal cord causing tingling leg weakness and urinary and fecal incontinence 32 Risk factors EditThe primary risk factors are obesity 33 age and family history Obese men have been found to have a 34 greater death rate from prostate cancer than those with normal weight 33 Prostate cancer is uncommon in men younger than 45 but becomes more common with advancing age 34 35 The average age at the time of diagnosis is 70 36 Men with high blood pressure are more likely to develop prostate cancer 37 A small increase in risk is associated with lack of exercise 38 Elevated blood testosterone levels 39 may increase risk Genetics Edit Genetics affects risk as suggested by associations with race family and specific gene variants 40 Up to 10 of prostate cancer is caused by inherited genes including 40 of early onset prostate cancers 41 Men with an affected first degree relative father or brother have more than twice the risk of developing prostate cancer and those with two first degree relatives have a five fold greater risk compared with men with no family history 41 This risk appears to be greater for men with an affected brother than for those with an affected father citation needed Increased risk also runs in some ethnic groups with African American men at particularly high risk having prostate cancer at higher rates and having more aggressive prostate cancers 41 In contrast the incidence and mortality rates for Hispanic men are one third lower than for non Hispanic whites Twin studies in Scandinavia suggest that 58 of prostate cancer risk can be explained by inherited factors 42 43 Many genes are involved in inherited risk for prostate cancer The first gene linked to inherited prostate cancer in families was hereditary prostate cancer gene 1 HPC1 44 45 Mutations within the HOXB13 gene can also carry strong risk for prostate cancer 46 47 Inherited genetic variation of the chromosome 8q24 locus one that is prominently observed through genome wide association study GWAS of both familial and sporadic prostate cancer can carry near Mendelian up to 20 fold risk for prostate cancer 48 This region encompasses regulatory elements non coding genes and the stem cell related POU5F1B gene Roughly 4 of families in which multiple men are affected by prostate cancer carry mutations in HOXB13 and another 4 carry mutations at 8q24 Mutations in BRCA1 and BRCA2 important risk factors for ovarian cancer and breast cancer in women have also been implicated 49 Large genome wide association studies have identified several dozen gene variants associated with increased prostate cancer risk together the gene variants are estimated to cause around 25 of prostate cancer cases 41 These variants include single nucleotide polymorphisms in the vitamin D receptor common in African Americans and in the androgen receptor CYP3A4 and CYP17 involved in testosterone synthesis and signaling 41 A number of somatic mutations acquired rather than inherited have also been defined in prostate tumors that drive their growth TMPRSS2 ETS gene family fusion specifically TMPRSS2 ERG or TMPRSS2 ETV1 4 promotes cancer cell growth 50 These fusions can arise via complex rearrangement chains called chromoplexy 51 Lifestyle Edit Plant based diets are associated with a lower risk for prostate cancer Switching to a plant based diet shows favorable results for cancer outcomes in men with prostate cancer Especially vegan diets consistently show favorable associations with prostate cancer risk and outcomes 52 People who consume high levels of dietary fats are at an increased risk of developing symptomatic prostate cancer as are those who consume high levels of polycyclic aromatic hydrocarbons from cooking red meats 41 Those with a diet rich in cruciferous vegetables genistein and lycopene found in tomatoes are at a reduced risk of symptomatic prostate cancer 41 Several dietary supplements have been studied and found not to impact prostate cancer risk including selenium vitamin C and vitamin E 53 The consumption of milk may be related to prostate cancer 54 55 A 2020 systematic review found the results on milk consumption and prostate cancer inconclusive but stated that individuals with higher risk may reduce or eliminate milk 56 A 2019 overview stated that the evidence that linked milk to higher rates of prostate cancer was inconsistent and inconclusive 57 Lower blood levels of vitamin D may increase risks 58 The data on the relationship between diet and prostate cancer are poor 59 However the rate of prostate cancer is linked to the consumption of the Western diet 59 Little if any evidence associates trans fat saturated fat and carbohydrate intake and prostate cancer 59 60 Evidence does not support a role for omega 3 fatty acids in preventing prostate cancer 59 61 Vitamin supplements appear to have no effect and some may increase the risk 20 59 High supplemental calcium intake has been linked to advanced prostate cancer 62 Fish may lower prostate cancer deaths but does not appear to affect occurrence 63 Some evidence supports lower rates of prostate cancer with a vegetarian diet 64 lycopene selenium 65 66 cruciferous vegetables soy beans and or other legumes 67 Regular exercise may slightly lower risk especially vigorous activity 67 68 Medication exposure Edit Some links have been established between prostate cancer and medications medical procedures and medical conditions 69 Statins may also decrease risk 70 Infection Edit Prostatitis infection or inflammation may increase risk In particular infection with the sexually transmitted infections Chlamydia gonorrhea or syphilis seems to increase risk 12 71 Papilloma virus has been proposed to have a potential role but as of 2015 the evidence was inconclusive 72 as of 2018 the increased risk was debated 73 Environment Edit US war veterans who had been exposed to Agent Orange had a 48 increased risk of prostate cancer recurrence following surgery 74 Sex Edit Although some evidence from prospective cohort studies indicates that frequent ejaculation may reduce prostate cancer risk 75 no randomized controlled trials reported this benefit 76 An association between vasectomy and prostate cancer was found but causality has not been established 77 Pathophysiology Edit The prostate is part of the male reproductive system that helps make and store seminal fluid In adult men a typical prostate is about 3 cm long and weighs about 20 g 78 It is located in the pelvis under the urinary bladder and in front of the rectum The prostate surrounds part of the urethra the tube that carries urine from the bladder during urination and semen during ejaculation 79 The prostate contains many small glands which make about 20 of the fluid constituting semen 80 Superiorly the prostate base is contiguous with the bladder outlet Inferiorly the prostate s apex heads in the direction of the urogenital diaphragm which is pointed anterio inferiorly 81 The prostate can be divided into four anatomic spaces peripheral central transitional and anterior fibromuscular stroma 82 The peripheral space contains the posterior and lateral portions of the prostate as well as the inferior portions of the prostate 83 The central space contains the superior portion of the prostate including the most proximal aspects of the urethra and bladder neck 84 The transitional space is located just anterior to the central space and includes urethra distal to the central gland urethra 85 The neurovascular bundles course along the posterolateral prostate surface and penetrate the prostatic capsule there as well 86 Most of the glandular tissue is found in the peripheral and central zones peripheral zone 70 80 of glandular tissue central zone 20 of glandular tissue 87 Some is found in the transitional space 5 of glandular tissue Thus most cancers that develop from glandular tissue are found in the peripheral and central spaces 88 while about 5 is found in the transitional space None is found in the anterior fibromuscular stroma since no glands are in that anatomic space The prostate glands require male hormones known as androgens to work properly Androgens include testosterone which is made in the testes 89 dehydroepiandrosterone made in the adrenal glands and dihydrotestosterone which is converted from testosterone within the prostate itself Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass citation needed Because of the prostate s location prostate diseases often affect urination ejaculation and rarely defecation In prostate cancer the cells of these glands mutate into cancer cells 90 Prostate cancer that has metastasized to the lymph nodes Prostate cancer that has metastasized to the bone Most prostate cancers are classified as adenocarcinomas or glandular cancers that begin when semen secreting gland cells mutate into cancer cells 91 The region of the prostate gland where the adenocarcinoma is most common is the peripheral zone Initially small clumps of cancer cells remain within otherwise normal prostate glands a condition known as carcinoma in situ or prostatic intraepithelial neoplasia PIN 92 Although no proof establishes that PIN is a cancer precursor it is closely associated with cancer 93 Over time these cells multiply and spread to the surrounding prostate tissue the stroma forming a tumor Eventually the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum or tumor cells may develop the ability to travel in the bloodstream and lymphatic system 94 Prostate cancer is considered a malignant tumor because it can invade other areas of the body This invasion is called metastasis 95 Prostate cancer most commonly metastasizes to the bones and lymph nodes and may invade the rectum bladder and lower ureters after local progression 96 The route of metastasis to bone is thought to be venous as the prostatic venous plexus draining the prostate connects with the vertebral veins 97 The prostate is a zinc accumulating citrate producing organ Transport protein ZIP1 is responsible for the transport of zinc into prostate cells 98 One of zinc s important roles is to change the cell s metabolism to produce citrate an important semen component 99 The process of zinc accumulation alteration of metabolism and citrate production is energy inefficient and prostate cells require enormous amounts of energy ATP to accomplish this task Prostate cancer cells are generally devoid of zinc Prostate cancer cells save energy by not making citrate and use the conserved energy to grow reproduce and spread 100 The absence of zinc is thought to occur via silencing the gene that produces ZIP1 It is called a tumor suppressor gene product for the gene SLC39A1 The cause of the epigenetic silencing is unknown 101 Strategies that transport zinc into transformed prostate cells effectively eliminate these cells in animals Zinc inhibits NF kB pathways is antiproliferative and induces apoptosis in abnormal cells 102 Unfortunately oral ingestion of zinc is ineffective since high concentrations of zinc into prostate cells is not possible without ZIP1 98 Loss of cancer suppressor genes early in prostatic carcinogenesis have been localized to chromosomes8p 10q 13q and 16q P53 mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings hence p53 mutations are a late event in the pathology Other tumor suppressor genes that are thought to play a role include PTEN and KAI1 Up to 70 percent of men with prostate cancer have lost one copy of the PTEN gene at the time of diagnosis 103 Relative frequency of loss of E cadherin and CD44 has also been observed Loss of the retinoblastoma RB protein induces androgen receptor deregulation in castration resistant prostate cancer by deregulating E2F1 expression 104 The factors that drive disease progression and clinical prognosis remain only partly understood but a variety of molecular determinants has been identified that appear to be involved The most important of these might be the tyrosine phosphatase ACP1 of which the expression might outperform the Gleason grading system for predicting disease course 105 Other molecules identified include the transcription factor RUNX2 which may prevent cancer cells from undergoing apoptosis 106 the PI3k Akt signaling cascade in conjunction with the transforming growth factor beta SMAD signaling cascade that also protect against apoptosis 107 Pim 1 is upregulated in prostate cancer 21 X linked inhibitor of apoptosis XIAP is hypothesized to promote cancer cell survival and growth 108 the Macrophage inhibitory cytokine 1 MIC 1 that stimulates the focal adhesion kinase FAK signaling pathway 109 Nevertheless it is fair to say that the molecular factors that determine why some patients have quiescent disease while others display prognosis remain largely obscure The androgen receptor helps cancer cells to survive 110 Prostate specific membrane antigen PSMA stimulates cancer development by increasing folate levels helping the cancer cells to survive and grow it increases available folates for use by hydrolyzing glutamated folates 111 Screening EditMain article Prostate cancer screening Prostate cancer screening searches for cancers in those without symptoms Options include the digital rectal exam and the PSA blood test 112 Such screening is controversial 113 and for many may lead to unnecessary disruption and possibly harmful consequences 114 Harms of population based screening primarily due to overdiagnosis the detection of latent cancers that would have otherwise not been discovered may outweigh the benefits 112 Others recommend shared decision making an approach where screening may occur after a physician consultation 115 The United States Preventive Services Task Force USPSTF suggests the decision whether to have PSA screening be based on consultation with a physician for men 55 to 69 years of age 15 USPSTF recommends against PSA screening after age 70 17 The Centers for Disease Control and Prevention endorsed USPSTF s conclusion 116 The American Society of Clinical Oncology and the American College of Physicians discourage screening for those who are expected to live less than 10 15 years while those with a greater life expectancy a decision should individually balance the potential risks and benefits 117 In general they concluded it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment 118 American Urological Association AUA 2013 guidelines call for weighing the uncertain benefits of screening against the known harms associated with diagnostic tests and treatment 119 The AUA recommends that shared decision making should control screening for those 55 to 69 and that screening should occur no more often than every two years 120 In the United Kingdom as of 2018 no program existed to screen for prostate cancer 16 The American Cancer Society s position regarding early detection by PSA testing is Research has not yet proven that the potential benefits of testing outweigh the harms of testing and treatment The American Cancer Society believes that men should not be tested without learning about what we know and don t know about the risks and possible benefits of testing and treatment Starting at age 50 45 if African American or brother or father suffered from condition before age 65 talk to your doctor about the pros and cons of testing so you can decide if testing is the right choice for you 121 Diagnosis Edit Prostate needle biopsy If already having grown large a prostate cancer may first be detected on CT scan Several tests can be used to gather information about the prostate and the urinary tract Digital rectal examination may allow a doctor to detect prostate abnormalities 122 Cystoscopy shows the urinary tract from inside the bladder using a thin flexible camera tube inserted in the urethra 123 A diagnosis of prostate cancer requires a biopsy of the prostate be taken and examined under a microscope by a pathologist Prostate biopsies are typically taken by a needle guided by imaging either transrectal ultrasound magnetic resonance imaging MRI or a combination of the two 124 During a biopsy a urologist or radiologist obtains tissue samples from the prostate via either the rectum or the perineum A biopsy gun inserts and removes special hollow core needles usually three to six on each side of the prostate in less than a second 125 Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization 126 Ultrasound imaging can be obtained transrectally and is used during prostate biopsies 127 Prostate cancer can be seen as a hypoechoic lesion in 60 of cases The other 40 of cancerous lesions are either hyperechoic or isoechoic On Color Doppler the lesions appear hypervascular 128 Antibiotics should be used to prevent complications such as fever urinary tract infections and sepsis 129 even if the most appropriate course or dose is undefined 130 About 55 of men report discomfort during prostate biopsy 131 Biopsies are examined under a microscope by a pathologist who determines the type and extent of cancerous cells present Cancers are first classified based on their appearance under a microscope Over 95 of prostate cancers are classified as adenocarcinomas resembling gland tissue with the rest largely squamous cell carcinoma resembling squamous cells a type of epithelial cell and transitional cell carcinoma resembling transitional cells 132 Tumor samples can be stained for the presence of PSA and other tumor markers to determine the origin of malignant cells that have metastasized 133 Next tumor samples are graded based on how much the tumor tissue differs from normal prostate tissue the more different the tumor appears the faster the tumor is likely to grow The Gleason grading system is commonly used where the pathologist assigns a number from 1 similar to prostate tissue to 5 least similar for the most common pattern observed under the microscope then does the same for the second most common pattern The sum of these two numbers is the Gleason score 132 The total scores of 2 through 5 are no longer commonly used in practice making the lowest score 6 and the highest score 10 Scores are commonly grouped into Gleason grade groups a score of 6 or lower is Gleason grade group 1 a score of 7 with the first number from the most common pattern 3 and the second number 4 is grade group 2 the reverse first number 4 second number 3 is grade group 3 a score of 8 is grade group 4 a score of 9 or 10 is grade group 5 132 Higher Gleason scores and higher grade groups represent cancer cases likely to be more aggressive with worse prognosis 132 Micrograph showing a prostate cancer conventional adenocarcinoma with perineural invasion H amp E stain Pie chart of histopathologic subdiagnoses of prostate cancer 134 Staging Edit Main article Prostate cancer staging Diagram showing T1 3 stages of prostate cancer After diagnosis of prostate cancer the tumor is staged to determine the extent of tumor growth and spread Prostate cancer is typically staged using the American Joint Committee on Cancer s AJCC three component TNM system with scores assigned for the extent of the tumor T spread to any lymph nodes N and the presence of metastases M 135 Scores of T1 and T2 represent tumors that remain within the prostate T1 is for tumors not detectable by imaging or digital rectal exam T2 is for tumors detectable by imaging or rectal exam but still confined within the prostate 136 T3 is for tumors that grow beyond the prostate T3a is for tumors with any extension outside the prostate T3b is for tumors that invade the adjacent seminal vesicles T4 is for tumors that have grown into organs beyond the seminal vesicles 136 The N and M scores are binary N1 represents any spread to the nearby lymph nodes M1 represents any metastases to other body sites 136 The AJCC then combines the TNM scores Gleason grade group and results of the PSA blood test to categorize cancer cases into one of four stages and their subdivisions Cancer cases with localized tumors T1 or T2 no spread N0 and M0 Gleason grade group 1 and PSA less than 10 ng mL are designated stage I Those with localized tumors no spread and PSA between 10 and 20 ng mL are desigated stage II subdivided into IIA for Gleason grade group 1 IIB for grade group 2 and IIC for grade group 3 or 4 Stage III is the designation for any of three higher risk factors IIIA is for a PSA level about 20 ng mL IIIB is for T3 or T4 tumors IIIC is for a Gleason grade group of 5 Stage IV is for cancers that have spread to lymph nodes N1 stage IVA or other organs M1 stage IVB 135 In the United Kingdom the Cambridge Prognostic Group CPG is used for categorising prostate cancer into 5 risk groups CPG1 to CPG5 137 Several tests can be used to look for evidence of spread Medical specialty professional organizations including the American Urological Association and European Association of Urology recommend against the use of PET scans CT scans or bone scans when a physician stages early prostate cancer with low risk for metastasis 138 139 140 141 142 Those tests would be appropriate in cases such as when a CT scan evaluates spread within the pelvis a bone scan looks for spread to the bones and endorectal coil magnetic resonance imaging evaluates the prostatic capsule and the seminal vesicles Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis the reverse of what is found in many other metastatic cancers 143 Approved radiopharmaceutical diagnostic agents used in PET fluciclovine 2016 Ga 68 PSMA 11 2020 piflufolastat 2021 In men with high risk localised prostate cancer staging with PSMA PET CT may be appropriate to detect nodal or distant metastatic spread In 2020 a randomised phase 3 trial compared Gallium 68 PSMA PET CT to standard imaging CT and bone scan It reported superior accuracy of Gallium 68 PSMA 11 PET CT 92 vs 65 higher significant change in management 28 vs 15 less equivocal uncertain imaging findings 7 vs 23 and lower radiation exposure 10 msV vs 19 mSv The study concluded that PSMA PET CT is a suitable replacement for conventional imaging 144 A PSMA scan is a positron emission tomography PET imaging technique which targets the overexpression of PSMA in prostate cancer tissue A range of radiopharmaceuticals have been developed with more under active research Gallium 68 68Ga PSMA 11 and fluorine 18 18F PSMA DCFPyL received FDA approval for PET CT imaging in prostate cancer in 2021 145 146 It has a role in evaluation of prostate cancer patients especially patients who may go on to receive lutetium 177 177Lu PSMA radioligand therapy 147 148 Sclerosis of the bones of the thoracic spine due to prostate cancer metastases CT image Sclerosis of the bones of the thoracic spine due to prostate cancer metastases CT image Sclerosis of the bones of the pelvis due to prostate cancer metastasesPrevention EditNo drug or vaccine is approved by regulatory agencies for the prevention of prostate cancer Several studies have shown 5a reductase inhibitors to reduce the incidence of prostate cancer however whether they reduce disease is not clear 53 Management EditMain article Management of prostate cancer The first decision is whether treatment is needed Low grade forms found in elderly men often grow so slowly that treatment is not required 149 Treatment may be inappropriate if a person has other serious health problems or is not expected to live long enough for symptoms to appear Approaches in which treatment is postponed are termed expectant management 149 Expectant management is divided into two approaches Watchful waiting which has palliative intent aims to treat symptoms only and active surveillance which has curative intent aims to prevent the cancer from advancing 149 Which option is best depends on disease stage the Gleason score and the PSA level Other important factors are age general health and a person s views about potential treatments and their possible side effects Because most treatments can have significant side effects such as erectile dysfunction and urinary incontinence treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations A 2017 review found that more research focused on person centered outcomes is needed to guide patients 150 A combination of treatment options is often recommended 151 152 153 Guidelines for specific clinical situations require estimation of life expectancy 154 As average life expectancy increases due to advances in the treatment of other diseases more patients will live long enough for their prostate cancer to express symptoms 155 An 18 item questionnaire was proposed to learn whether patients have adequate knowledge and understanding of their treatment options In one 2015 study most of those who were newly diagnosed correctly answered fewer than half of the questions 154 The widespread use of PSA screening in the US has resulted in diagnosis at earlier age and cancer stage but almost all cases are still diagnosed after age 65 while about 25 are diagnosed after age 75 156 Though US National Comprehensive Cancer Network guidelines recommend using life expectancy to help make treatment decisions in practice many elderly patients are not offered curative treatment options such as radical prostatectomy or radiation therapy and are instead treated with hormonal therapy or watchful waiting 157 Surveillance Edit Main article Active surveillance of prostate cancer Many men diagnosed with low risk prostate cancer are eligible for active surveillance The tumor is carefully observed over time with the intention of initiating treatment if signs of progression appear 158 Active surveillance is not synonymous with watchful waiting a term which implies no treatment or specific program of monitoring with the assumption that only palliative treatment would be used if advanced symptomatic disease develops 149 Active surveillance involves monitoring the tumor for growth or symptoms which trigger treatment The monitoring process may involve PSA tests digital rectal examination or repeated biopsies every few months 159 The goal of active surveillance is to postpone treatment and avoid overtreatment and its side effects given a slow growing or self limited tumor that in most people is unlikely to cause problems 160 This approach is not used for aggressive cancers and may cause anxiety for people who wrongly believe that all cancers are deadly or that their condition is life threatening 161 Between 50 and 75 of patients die from other causes without experiencing prostate symptoms 162 In localized disease based on long term follow up radical prostatectomy results in significantly improved oncological outcomes when compared with watchful waiting 163 Prostatectomy is associated with increased rates of urinary incontinence and erectile dysfunction but these findings are based primarily on men diagnosed before widespread PSA screening and cannot be highly generalized 163 When compared to active monitoring surveillance on follow up at ten years radical prostatectomy probably has similar outcomes for disease specific survival and probably reduces risk of disease progression and spreading 163 Urinary and sexual function are probably decreased in patients treated with radical prostatectomy 163 Active treatment Edit Both surgical and nonsurgical treatments are available but treatment can be difficult and combinations can be used 164 Treatment by external beam radiation therapy brachytherapy cryosurgery high intensity focused ultrasound and prostatectomy are in general offered to men whose cancer remains within the prostate 165 Hormonal therapy and chemotherapy are often reserved for metastatic disease Exceptions include local or metastasis directed therapy with radiation may be used for advanced tumors with limited metastasis 166 Hormonal therapy is used for some early stage tumors Cryotherapy the process of freezing the tumor hormonal therapy and chemotherapy may be offered if initial treatment fails and the cancer progresses 167 Sipuleucel T a cancer vaccine was reported to offer a four month increase in survival in metastatic prostate cancer 168 but the marketing authorisation for it was withdrawn on 19 May 2015 If radiation therapy fails radical prostatectomy may be an option 169 though it is a technically challenging surgery 170 However radiation therapy after surgical failure may have many complications 171 It is associated with a small increase in bladder and colon cancer 172 Radiotherapy and surgery appear to result in similar outcomes with respect to bowel erectile and urinary function after five years 173 Nonsurgical treatment Edit Non surgical treatment may involve radiation therapy chemotherapy hormonal therapy external beam radiation therapy and particle therapy high intensity focused ultrasound or some combination 174 175 Prostate cancer that persists when testosterone levels are lowered by hormonal therapy is called castrate resistant prostate cancer CRPC 176 177 Many early stage cancers need normal levels of testosterone to grow but CRPC does not Previously considered hormone refractory prostate cancer or androgen independent prostate cancer the term CRPC emerged because these cancers show reliance upon hormones particularly testosterone for androgen receptor activation 178 179 The cancer chemotherapeutic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months 180 181 A second line chemotherapy treatment is cabazitaxel 182 A combination of bevacizumab docetaxel thalidomide and prednisone appears effective in the treatment of CRPC 183 Immunotherapy treatment with sipuleucel T in CRPC appeared to increase survival by four months 184 However marketing authorisation for sipuleucel T was withdrawn on 19 May 2015 The second line hormonal therapy abiraterone increases survival by about 4 6 months 185 Enzalutamide is another second line hormonal agent with a five month survival advantage Both abiraterone and enzalutamide are currently in clinical trials in those with CRPC who have not previously received chemotherapy 186 187 Not all patients respond to androgen signaling blocking drugs Certain cells with characteristics resembling stem cells remain unaffected 188 189 Therefore the desire to improve CRPC outcomes resulted in increasing doses or combination therapy with synergistic androgen signaling blocking agents 190 But even these combination will not affect stem like cells that do not exhibit androgen signaling 191 For patients with metastatic prostate cancer that has spread to their bones doctors use a variety of bone modifying agents to prevent skeletal complications and support the formation of new bone mass 192 Zoledronic acid a bisphosphonate and denosumab a RANK ligand inhibitor appear to be effective agents but are associated with more frequent and serious adverse events 192 Surgery Edit Radical prostatectomy is considered the mainstay of surgical treatment of prostate cancer where the surgeon removes the prostate seminal vesicles and surrounding lymph nodes 193 It can be done by an open technique a skin incision at the lower abdomen or laparoscopically Radical retropubic prostatectomy is the most commonly used open surgical technique 194 Robotic assisted prostatectomy has become common 195 Men with localized prostate cancer having laparoscopic radical prostatectomy or robotic assisted radical prostatectomy might have shorter stays in the hospital and get fewer blood transfusions than men undergoing open radical prostatectomy 196 How these treatments compare with regard to overall survival or recurrence free survival is unknown 196 Transurethral resection of the prostate is the standard surgical treatment for benign enlargement of the prostate 195 In prostate cancer this procedure can be used to relieve symptoms of urinary retention caused by a large prostate tumor but it is not used to treat the cancer itself The procedure is done under spinal anesthesia a resectoscope is inserted inside the penis and the extra prostatic tissue is cut to clear the way for the urine to pass 90 Uses of MRI Edit Prostate MRI is also used for surgical planning for robotic prostatectomy 197 It helps surgeons decide whether to resect or spare the neurovascular bundle determine return to urinary continence and help assess surgical difficulty 197 MRI is used in other types of treatment planning for both focal therapy 198 and radiotherapy 199 MRI can also be used to target areas for research sampling in biobanking 200 201 Complications Edit The two main complications encountered after prostatectomy and prostate radiotherapy are erectile dysfunction and urinary incontinence mainly stress type Most men regain continence within 6 to 12 months after the operation so doctors usually wait at least one year before resorting to invasive treatments 202 Stress urinary incontinence usually happens after prostate surgery or radiation therapy due to factors that include damage to the urethral sphincter or surrounding tissue and nerves 203 The prostate surrounds the urethra a muscular tube that closes the urinary bladder 204 Any of the mentioned reasons can lead to incompetent closure of the urethra and hence incontinence 205 Initial therapy includes bladder training lifestyle changes kegel exercises and the use of incontinence pads More invasive surgical treatment can include the insertion of a urethral sling or an artificial urinary sphincter which is a mechanical device that mimics the function of the urethral sphincter and is activated manually by the patient through a switch implanted in the scrotum 206 The latter is considered the gold standard in patients with moderate or severe stress urinary incontinence 207 Erectile dysfunction happens in different degrees in nearly all men who undergo prostate cancer treatment including radiotherapy or surgery however within one year most of them will notice improvement If nerves were damaged this progress may not take place Pharmacological treatment includes PDE 5 inhibitors such as viagra or cialis or injectable intracavernous drugs injected directly into the penis prostaglandin E1 and vasoactive drug mixtures Other nonpharmacological therapy includes vacuum constriction devices and penile implants 208 Psychological Edit Psychological interventions such as psychoeducation cognitive behavioural therapy CBT and mindfulness are recommended for the management of mental and emotional complications of disease symptoms and those associated with active treatment 209 210 Due to limited research and inadequate methodological rigor of published literature solid recommendations cannot be made on the effectiveness of mindfulness in men with prostate cancer 211 Prognosis EditMany prostate cancers are not destined to be lethal and most men will ultimately not die as a result of the disease Mortality varies widely across geography and other elements In the United States five year survival rates range from 29 distant metastases to 100 local or regional tumors 212 In Japan the fatality rate rose to 8 6 100 000 in 2000 213 In India in the 1990s half of those diagnosed with local cancer died within 19 years 214 One study reported that African Americans have 50 60 times more deaths than found in Shanghai China 215 In Nigeria 2 of men develop prostate cancer and 64 of them are dead after 2 years 216 Most Nigerian men present with metastatic disease with a typical survival of 40 months 217 In patients who undergo treatment the most important clinical prognostic indicators of disease outcome are the stage pretherapy PSA level and Gleason score 218 The higher the grade and the stage the poorer the prognosis Nomograms can be used to calculate the estimated risk of the individual patient The predictions are based on the experience of large groups of patients 219 A complicating factor is that the majority of patients have multiple independent tumor foci upon diagnosis and these foci have independent genetic changes and molecular features 220 Because of this extensive inter focal heterogeneity it is a risk that the prognostication is set based on the wrong tumor focus An important aspect of decision making on the value of treatment is how to balance prognosis from prostate cancer with other causes of mortality and the morbidity of treatment The PREDICT Prostate algorithm 221 is a multivariable prognostic model that provides individualised cancer specific and overall long term survival estimates in early stage non metastatic PCa patients 222 In addition to the use of routinely available preoperative clinical pathological variables such as PSA biopsy Gleason score ISUP grade group and clinical T stage the PREDICT Prostate tool also includes the impact of patient characteristics age and comorbidity status and radical treatment radical prostatectomy or radiotherapy on survival The tool provides patients with estimated survival rates after treatment in the context of absolute mortality rate which allows patients to make an informed decision as to the value of treatment and its potential side effects Thurtle et al 223 performed an external validation of their previously published PREDICT Prostate model 224 The tool outperformed other widely used models and was proven to have high c indices for all cause and PCa specific mortality and the model calibration was good and remained accurate within the treatment subgroups Recent work has also shown that it significantly alters clinician treatment recommendations and improves patients confidence in decision making and in their understanding of mortality risks from a new prostate cancer diagnosis 225 226 Predict Prostate is endorsed for use as a decision aid for prostate cancer by the UK National Institute for Health and Care Excellence 227 Androgen ablation therapy causes remission in 80 90 of patients undergoing therapy resulting in a median progression free survival of 12 to 33 months After remission an androgen independent phenotype typically emerges wherein the median overall survival is 23 37 months from the time of initiation of androgen ablation therapy 228 How androgen independence is established and how it re establishes progression is unclear 229 Classification systems Edit Micrograph of prostate adenocarcinoma acinar type the most common type of prostate cancer Needle biopsy H amp E stain Several tools are available to help predict outcomes such as pathologic stage and recurrence after surgery or radiation therapy Most combine stage grade and PSA level and some include the number or percentage of biopsy cores positive age and or other information The D Amico classification stratifies men by low intermediate or high risk based on stage grade and PSA It is used widely in clinical practice and research settings 230 The major downside to the three level system is that it does not account for multiple adverse parameters e g high Gleason score and high PSA in stratifying patients The Partin tables 231 predict pathologic outcomes margin status extraprostatic extension and seminal vesicle invasion based on the same three variables and are published as lookup tables The Kattan nomograms predict recurrence after surgery and or radiation therapy based on data available at the time of diagnosis or after surgery 232 The Kattan score represents the likelihood of remaining free of disease at a given time interval following treatment The UCSF Cancer of the Prostate Risk Assessment CAPRA score predicts both pathologic status and recurrence after surgery It offers accuracy comparable to the Kattan preoperative nomogram and can be calculated without tables or a calculator Points are assigned based on PSA grade stage age and percentage of cores positive the sum yields a 0 10 score with every two points representing roughly a doubling of risk of recurrence The CAPRA score was derived from community based data in the CaPSURE database 233 It has been validated among over 10 000 prostatectomy patients including patients from CaPSURE 234 the SEARCH registry representing data from several Veterans Health Administration and military medical centers 235 a multi institutional cohort in Germany 236 and the prostatectomy cohort at Johns Hopkins University 237 More recently it has been shown to predict metastasis and mortality following prostatectomy radiation therapy watchful waiting or androgen deprivation therapy 238 The UK National Institute for Health and Care Excellence guidelines recommends use of the Cambridge Prognostic Groups CPG 5 tier model when determining treatment options The rationale for the change related to recent evidence which suggests that 5 tier risk stratification model was better at predicting prostate cancer specific mortality than older 3 tier models 239 The CPG model has been tested and validated in studies including gt 80 000 men 240 241 242 The NICE CPG model and treatment recommendations can be viewed at the NICE guideline website 243 Life expectancy Edit Life expectancy projections are averages for an entire male population and many medical and lifestyle factors modify these numbers 244 For example studies have shown that a 40 year old man will lose 3 1 years of life if he is overweight BMI 25 29 and 5 8 years of life if he is obese BMI 30 or more compared to men of normal weight If he is both overweight and a smoker he will lose 6 7 years and if obese and a smoker he will lose 13 7 years 245 No evidence shows that either surgery or beam radiation has an advantage over the other in this regard The lower death rates reported with surgery appear to occur because surgery is more likely to be offered to younger men with less severe cancers Insufficient information is available to determine whether seed radiation extends life more readily than the other treatments but data so far do not suggest that it does 246 Men with low grade disease Gleason 2 4 were unlikely to die of prostate cancer within 15 years of diagnosis 247 Older men age 70 75 with low grade disease had a roughly 20 overall survival at 15 years due to deaths from competing causes Men with high grade disease Gleason 8 10 experienced high mortality within 15 years of diagnosis regardless of their age 248 Epidemiology Edit Age standardized death from prostate cancer per 100 000 inhabitants in 2004 249 no data lt 4 4 8 8 12 12 16 16 20 20 24 24 28 28 32 32 36 36 40 40 44 gt 44 This section needs to be updated Relevant discussion may be found on the talk page Please help update this article to reflect recent events or newly available information February 2023 As of 2012 prostate cancer is the second most frequently diagnosed cancer at 15 of all male cancers 250 and the sixth leading cause of cancer death in males worldwide 251 In 2010 prostate cancer resulted in 256 000 deaths up from 156 000 deaths in 1990 252 Rates of prostate cancer vary widely Rates vary widely between countries It is least common in South and East Asia and more common in Europe North America Australia and New Zealand 253 Prostate cancer is least common among Asian men and most common among Black men with white men in between 254 255 Prostate cancer is common with age but a minority of men with prostate cancer will ever have symptoms of the disease or have their prostate cancer diagnosed More than 70 of men autopsied in their 70s have cancer in their prostate however 1 in 8 men are diagnosed with prostate cancer Of those with prostate cancer around 2 die of the disease 256 United States Edit This section needs additional citations for verification Please help improve this article by adding citations to reliable sources in this section Unsourced material may be challenged and removed August 2020 Learn how and when to remove this template message New cases and deaths from prostate cancer in the United States per 100 000 males between 1975 and 2014 Prostate cancer is the third leading cause of cancer death in men exceeded by lung cancer and colorectal cancer It accounts for 19 of all male cancers and 9 of male cancer related deaths 257 Cases ranged from an estimated 230 000 in 2005 258 to an estimated 164 690 In 2018 259 Deaths held steady around 30 000 in 2005 258 and 29 430 in 2018 Age adjusted incidence rates increased steadily from 1975 through 1992 with particularly dramatic increases associated with the spread of PSA screening in the late 1980s later followed by a fall in incidence A decline in early stage incidence rates from 2011 to 2012 19 in men aged 50 years and older persisted through 2013 6 Declines in mortality rates in certain jurisdictions may reflect the interaction of PSA screening and improved treatment 260 The estimated lifetime risk is about 14 0 and the lifetime mortality risk is 2 6 261 Between 2005 and 2011 the proportion of disease diagnosed at a locoregional stage was 93 for whites and 92 for African Americans 262 the proportion of disease diagnosed at a late stage was 4 for European Americans and 5 for African Americans 262 Prostate cancer is more common in the African American population than the European American population 3 An autopsy study of White and Asian men also found an increase in occult prostate cancer with age 263 reaching nearly 60 in men older than 80 years More than 50 of cancers in Asian men and 25 of cancers in White men had a Gleason score of 7 or greater 264 suggesting that Gleason score may be an imprecise indicator of clinically insignificant cases 265 Canada Edit Prostate cancer is the third leading type of cancer in Canadian men In 2016 around 4 000 died and 21 600 men were diagnosed with prostate cancer 113 Europe Edit In Europe in 2012 it was the third most diagnosed cancer after breast and colorectal cancers at 417 000 cases 266 In the United Kingdom it is the second most common cause of cancer death after lung cancer where around 35 000 cases are diagnosed every year of which around 10 000 are fatal 267 History EditThe prostate was first described by Venetian anatomist Niccolo Massa in 1536 and illustrated by Flemish anatomist Andreas Vesalius in 1538 268 Prostate cancer was identified in 1853 269 270 It was initially considered a rare disease probably because of shorter life expectancies and poorer detection methods in the 19th century The first treatments were surgeries to relieve urinary obstruction 271 Removal of the gland was first described in 1851 272 and radical perineal prostatectomy was first performed in 1904 by Hugh H Young at Johns Hopkins Hospital 273 269 Surgical removal of the testes orchiectomy to treat prostate cancer was first performed in the 1890s with limited success 274 Transurethral resection of the prostate TURP replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh 275 This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function In 1941 Charles B Huggins published studies in which he used estrogen to oppose testosterone production in men with metastatic prostate cancer This discovery of chemical castration won Huggins the 1966 Nobel Prize in Physiology or Medicine 276 The role of the gonadotropin releasing hormone GnRH in reproduction was determined by Andrzej W Schally and Roger Guillemin who shared the 1977 Nobel Prize in Physiology or Medicine for this work GnRH receptor agonists such as leuprorelin and goserelin were subsequently developed and used to treat prostate cancer 277 278 Radiation therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium implants External beam radiotherapy became more popular as stronger X ray radiation sources became available in the middle of the 20th century Brachytherapy with implanted seeds for prostate cancer was first described in 1983 279 Systemic chemotherapy for prostate cancer was first studied in the 1970s The initial regimen of cyclophosphamide and 5 fluorouracil was quickly joined by regimens using other systemic chemotherapy drugs 280 Enzalutamide gained FDA approval in 2012 for the treatment of castration resistant prostate cancer CRPC 186 187 Alpharadin won FDA approval in 2013 under the priority review program 281 In 2006 a previously unknown retrovirus Xenotropic MuLV related virus XMRV was associated with human prostate tumors 282 but PLOS Pathogens retracted the article in 2012 282 Society and culture EditMen with prostate cancer generally encounter significant disparities in awareness funding media coverage and research and therefore inferior treatment and poorer outcomes compared to other cancers of equal prevalence 283 In 2001 The Guardian noted that Britain had 3 000 nurses specializing in breast cancer compared to a single nurse for prostate cancer 284 Waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer 285 A 2007 report by the U S based National Prostate Cancer Coalition stated that prostate cancer drugs were outnumbered seven to one by breast cancer drugs 286 The Times also noted an anti male bias in cancer funding with a four to one discrepancy in the United Kingdom by both the government and by cancer charities such as Cancer Research UK 283 287 Critics cite such figures when claiming that women s health is favored over men s health 288 Disparities extend into detection with governments failing to fund or mandate prostate cancer screening while fully supporting breast cancer programs For example a 2007 report found 49 U S states mandate insurance coverage for routine breast cancer screening compared to 28 for prostate cancer 289 Prostate cancer experiences significantly less media coverage than other equally prevalent cancers outcovered 2 6 1 by breast cancer 283 Prostate Cancer Awareness Month takes place in September in a number of countries A light blue ribbon is used to promote the cause 290 291 Research EditCastration resistant prostate cancer Edit Castration resitant prostate cancer is prostate cancer that progresses despite androgen depletion therapy 292 Enzalutamide is a nonsteroidal antiandrogen NSAA 186 187 It has been used with abiraterone in studies involving Whole genome sequencing that have shown how androgen receptors acquire resistance to them which determines the use of new therapies against this pathology such as degraders of the protein or of the N terminal domain of this receptor This has been seen thanks to the sequencing of circulating tumor DNA in patients 293 Alpharadin uses bone targeted Radium 223 isotopes to kill cancer cells by alpha radiation 294 unreliable medical source PARP inhibitor olaparib is an approved breast ovarian cancer drug that is undergoing clinical trials 295 Also in trials for CRPC are checkpoint inhibitor ipilimumab CYP17 inhibitor galeterone TOK 001 and immunotherapy PROSTVAC 295 All medications for CRPC block androgen receptor AR signaling via direct or indirect targeting of the AR ligand binding domain LBD AR belongs to the steroid nuclear receptor family 296 Development of the prostate is dependent on androgen signaling mediated through AR and AR is also important for disease progression 297 Molecules that could successfully target alternative domains have emerged 296 Such therapies could provide an advantage particularly in treating prostate cancers that are resistant to current therapies 296 Evolution Edit Sequencing techniques in addition to reflecting the mechanisms of resistance to treatment through the circulating tumor DNA distinguish between the evolutionary history of this cancer when it metastasizes and the temporal subclonal dynamics determining how the tumor is found when it is diagnosed 293 Pre clinical Edit Arachidonate 5 lipoxygenase has been identified as playing a significant role in the survival of prostate cancer cells 298 299 300 Medications that target this enzyme are undergoing development 298 299 300 In particular arachidonate 5 lipoxygenase inhibitors produce massive rapid programmed cell death in prostate cancer cells 298 299 300 Galectin 3 is another potential target 301 Aberrant glycan profiles have been described in prostate cancer 302 303 and studies have found specific links between the galectin signature and prostate cancer 304 305 The PIM kinase family is another potential target for selective inhibition A number of related drugs are under development It has been suggested the most promising approach may be to co target this family with other pathways including PI3K 21 Cancer models Edit Scientists have established prostate cancer cell lines to investigate disease progression LNCaP PC 3 PC3 and DU 145 DU145 are commonly used prostate cancer cell lines 306 The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma PC 3 and DU 145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain respectively LNCaP cells express AR but PC 3 and DU 145 cells express very little or no AR citation needed The proliferation of LNCaP cells is androgen dependent but the proliferation of PC 3 and DU 145 cells is androgen insensitive Elevation of AR expression is often observed in advanced prostate tumors in patients 307 308 Some androgen independent LNCaP sublines have been developed from the ATCC androgen dependent LNCaP cells after androgen deprivation for study of prostate cancer progression These androgen independent LNCaP cells have elevated AR expression and express prostate specific antigen upon androgen treatment Paradoxically androgens inhibit the proliferation of these androgen independent prostate cancer cells 309 310 311 Diagnosis Edit One active research area and non clinically applied investigations involves non invasive methods of tumor detection 312 A molecular test that detects the presence of cell associated PCA3 mRNA in fluid obtained from the prostate and first void urine sample is under investigation PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over expressed in prostate cancer cells The test result is currently reported as a specimen ratio of PCA3 mRNA to PSA mRNA 313 The PCA3 test attempts to help decide whether in men suspected of having prostate cancer especially if an initial biopsy fails to explain the elevated serum PSA a biopsy rebiopsy is needed The higher the expression of PCA3 in the sample the greater the likelihood of a positive biopsy 314 The CDC s Evaluation of Genomic Applications in Practice and Prevention Working Group discourages clinical use 315 See also EditProstate Cancer Foundation Testicular cancerReferences Edit a b c d Prostate Cancer Treatment PDQ Health Professional Version National Cancer Institute 2014 04 11 Archived from the original on 5 July 2014 Retrieved 1 July 2014 a b c d e f g h i j Prostate Cancer Treatment PDQ Patient Version National Cancer Institute 2014 04 08 Archived from the original on 5 July 2014 Retrieved 1 July 2014 a b c d e f g h i j k l Chapter 5 11 World Cancer Report World Health Organization 2014 ISBN 978 9283204299 a b SEER Stat Fact Sheets Prostate Cancer NCI Archived from the original on 6 July 2014 Retrieved 18 June 2014 a b c Bray F Ferlay J Soerjomataram I Siegel RL Torre LA Jemal A November 2018 Global cancer statistics 2018 GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA 68 6 394 424 doi 10 3322 caac 21492 PMID 30207593 S2CID 52188256 Prostate cancer Symptoms and causes Mayo Clinic Retrieved 2023 02 11 What Is Prostate Cancer www cancer org Retrieved 2023 02 11 Luining WI Cysouw MC Meijer D Hendrikse NH Boellaard R Vis AN Oprea Lager DE February 2022 Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer Cancers 14 5 1169 doi 10 3390 cancers14051169 PMC 8909566 PMID 35267481 What Is Prostate Cancer www cancer org Retrieved 2022 09 28 Kalish LA McDougal WS McKinlay JB November 2000 Family history and the risk of prostate cancer Urology 56 5 803 806 doi 10 1016 S0090 4295 00 00780 9 PMID 11068306 Koh KA Sesso HD Paffenbarger RS Lee IM December 2006 Dairy products calcium and prostate cancer risk British Journal of Cancer 95 11 1582 1585 doi 10 1038 sj bjc 6603475 PMC 2360740 PMID 17106437 a b Caini S Gandini S Dudas M Bremer V Severi E Gherasim A August 2014 Sexually transmitted infections and prostate cancer risk a systematic review and meta analysis Cancer Epidemiology 38 4 329 338 doi 10 1016 j canep 2014 06 002 PMID 24986642 Lee MV Katabathina VS Bowerson ML Mityul MI Shetty AS Elsayes KM et al 2016 BRCA associated Cancers Role of Imaging in Screening Diagnosis and Management Radiographics 37 4 1005 1023 doi 10 1148 rg 2017160144 PMID 28548905 Prostate Cancer Treatment National Cancer Institute 6 February 2018 Retrieved 1 March 2018 Controversy exists regarding the value of screening reported no clear evidence that screening for prostate cancer decreases the risk of death from prostate cancer a b Catalona WJ March 2018 Prostate Cancer Screening The Medical Clinics of North America 102 2 199 214 doi 10 1016 j mcna 2017 11 001 PMC 5935113 PMID 29406053 a b PSA testing nhs uk 3 January 2015 Retrieved 5 March 2018 a b Final Recommendation Statement Prostate Cancer Screening www uspreventiveservicestaskforce org US Preventive Services Task Force USPSTF Retrieved 30 August 2018 Grossman DC Curry SJ Owens DK Bibbins Domingo K Caughey AB Davidson KW et al May 2018 Screening for Prostate Cancer US Preventive Services Task Force Recommendation Statement JAMA 319 18 1901 1913 doi 10 1001 jama 2018 3710 PMID 29801017 Cabarkapa S Perera M McGrath S Lawrentschuk N December 2016 Prostate cancer screening with prostate specific antigen A guide to the guidelines Prostate International 4 4 125 129 doi 10 1016 j prnil 2016 09 002 PMC 5153437 PMID 27995110 a b Stratton J Godwin M June 2011 The effect of supplemental vitamins and minerals on the development of prostate cancer a systematic review and meta analysis Family Practice 28 3 243 252 doi 10 1093 fampra cmq115 PMID 21273283 a b c Luszczak S Kumar C Sathyadevan VK Simpson BS Gately KA Whitaker HC Heavey S January 2020 PIM kinase inhibition co targeted therapeutic approaches in prostate cancer Signal Transduction and Targeted Therapy 5 1 7 doi 10 1038 s41392 020 0109 y PMC 6992635 PMID 32296034 Chapter 1 1 World Cancer Report World Health Organization 2014 ISBN 978 9283204299 a b Baade PD Youlden DR Krnjacki LJ February 2009 International epidemiology of prostate cancer geographical distribution and secular trends Molecular Nutrition amp Food Research 53 2 171 184 doi 10 1002 mnfr 200700511 PMID 19101947 Prostate Cancer Signs and Symptoms www cancer org Retrieved 2023 02 11 Leslie SW Soon Sutton TL Sajjad H Siref LE Prostate Cancer 2020 Oct 28 In StatPearls Internet Treasure Island FL StatPearls Publishing PMID 29261872 a b Miller DC Hafez KS Stewart A Montie JE Wei JT September 2003 Prostate carcinoma presentation diagnosis and staging an update form the National Cancer Data Base Cancer 98 6 1169 1178 doi 10 1002 cncr 11635 hdl 2027 42 34379 PMID 12973840 S2CID 22077473 Advanced prostate cancer Prostate Cancer UK Retrieved 2023 02 11 Henninger S Neusser S Lorenz C Bitzer EM December 2014 Prostate cancer in routine healthcare health related quality of life after inpatient treatment Der Urologe Ausg A 53 12 1793 1799 doi 10 1007 s00120 014 3615 0 PMID 25297490 Bauer RM 2016 Urinary Dysfunction in Prostate Cancer Male Slings In Sandhu JS ed Urinary Dysfunction in Prostate Cancer Urinary Dysfunction in Prostate Cancer A Management Guide Cham Springer International Publishing pp 53 69 doi 10 1007 978 3 319 23817 3 4 ISBN 978 3 319 23817 3 Retrieved 2022 04 28 Advanced prostate cancer Prostate Cancer UK Retrieved 2023 02 11 Liu Z Murphy SF Huang J Zhao L Hall CC Schaeffer AJ et al July 2020 A novel immunocompetent model of metastatic prostate cancer induced bone pain The Prostate 80 10 782 794 doi 10 1002 pros 23993 PMC 7375026 PMID 32407603 van der Cruijsen Koeter IW Vis AN Roobol MJ Wildhagen MF de Koning HJ van der Kwast TH Schroder FH July 2005 Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer section rotterdam The Journal of Urology 174 1 121 125 doi 10 1097 01 ju 0000162061 40533 0f PMID 15947595 a b Calle EE Rodriguez C Walker Thurmond K Thun MJ April 2003 Overweight obesity and mortality from cancer in a prospectively studied cohort of U S adults The New England Journal of Medicine 348 17 1625 1638 doi 10 1056 NEJMoa021423 PMID 12711737 S2CID 22714795 Maistro S Xavier CD Serio PA Katayama ML Roela RA Koike Folgueira MA 2019 05 20 Cancer driver genes in prostate cancer from young men Journal of Clinical Oncology 37 15 suppl e16586 doi 10 1200 JCO 2019 37 15 suppl e16586 ISSN 0732 183X S2CID 190897312 Smith CV Bauer JJ Connelly RR Seay T Kane C Foley J et al December 2000 Prostate cancer in men age 50 years or younger a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database The Journal of Urology 164 6 1964 1967 doi 10 1016 S0022 5347 05 66929 7 PMID 11061892 Hankey BF Feuer EJ Clegg LX Hayes RB Legler JM Prorok PC et al June 1999 Cancer surveillance series interpreting trends in prostate cancer part I Evidence of the effects of screening in recent prostate cancer incidence mortality and survival rates Journal of the National Cancer Institute 91 12 1017 1024 doi 10 1093 jnci 91 12 1017 PMID 10379964 Martin RM Vatten L Gunnell D Romundstad P March 2010 Blood pressure and risk of prostate cancer Cohort Norway CONOR Cancer Causes amp Control 21 3 463 472 doi 10 1007 s10552 009 9477 x PMID 19949849 S2CID 30484327 Friedenreich CM Neilson HK Lynch BM September 2010 State of the epidemiological evidence on physical activity and cancer prevention European Journal of Cancer 46 14 2593 2604 doi 10 1016 j ejca 2010 07 028 PMID 20843488 Gann PH Hennekens CH Ma J Longcope C Stampfer MJ August 1996 Prospective study of sex hormone levels and risk of prostate cancer Journal of the National Cancer Institute 88 16 1118 1126 doi 10 1093 jnci 88 16 1118 PMID 8757191 Prostate cancer Genetics Home Reference Retrieved 1 May 2020 a b c d e f g Scher amp Eastham 2022 Epidemiology Lichtenstein P Holm NV Verkasalo PK Iliadou A Kaprio J Koskenvuo M et al July 2000 Environmental and heritable factors in the causation of cancer analyses of cohorts of twins from Sweden Denmark and Finland The New England Journal of Medicine 343 2 78 85 doi 10 1056 NEJM200007133430201 PMID 10891514 Hjelmborg JB Scheike T Holst K Skytthe A Penney KL Graff RE et al November 2014 The heritability of prostate cancer in the Nordic Twin Study of Cancer Cancer Epidemiology Biomarkers amp Prevention 23 11 2303 2310 doi 10 1158 1055 9965 EPI 13 0568 PMC 4221420 PMID 24812039 S2CID 29554506 Smith JR Freije D Carpten JD Gronberg H Xu J Isaacs SD et al November 1996 Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome wide search Science 274 5291 1371 1374 Bibcode 1996Sci 274 1371S doi 10 1126 science 274 5291 1371 PMID 8910276 S2CID 42684655 Carpten J Nupponen N Isaacs S Sood R Robbins C Xu J et al February 2002 Germline mutations in the ribonuclease L gene in families showing linkage with HPC1 Nature Genetics 30 2 181 184 doi 10 1038 ng823 PMID 11799394 S2CID 2922306 Ewing CM Ray AM Lange EM Zuhlke KA Robbins CM Tembe WD et al January 2012 Germline mutations in HOXB13 and prostate cancer risk The New England Journal of Medicine 366 2 141 149 doi 10 1056 NEJMoa1110000 PMC 3779870 PMID 22236224 Dupont WD Breyer JP Johnson SH Plummer WD Smith JR May 2021 Prostate cancer risk variants of the HOXB genetic locus Scientific Reports 11 1 11385 Bibcode 2021NatSR 1111385D doi 10 1038 s41598 021 89399 7 PMC 8167119 PMID 34059701 S2CID 235269663 Dupont WD Breyer JP Plummer WD Chang SS Cookson MS Smith JA et al March 2020 8q24 genetic variation and comprehensive haplotypes altering familial risk of prostate cancer Nature Communications 11 1 1523 Bibcode 2020NatCo 11 1523D doi 10 1038 s41467 020 15122 1 PMC 7089954 PMID 32251286 S2CID 214606533 Struewing JP Hartge P Wacholder S Baker SM Berlin M McAdams M et al May 1997 The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews The New England Journal of Medicine 336 20 1401 1408 doi 10 1056 NEJM199705153362001 PMID 9145676 Beuzeboc P Soulie M Richaud P Salomon L Staerman F Peyromaure M et al December 2009 Fusion genes and prostate cancer From discovery to prognosis and therapeutic perspectives Progres en Urologie in French 19 11 819 824 doi 10 1016 j purol 2009 06 002 PMID 19945666 Baca SC Prandi D Lawrence MS Mosquera JM Romanel A Drier Y et al April 2013 Punctuated evolution of prostate cancer genomes Cell 153 3 666 677 doi 10 1016 j cell 2013 03 021 PMC 3690918 PMID 23622249 Gupta N Patel HD Taylor J Borin JF Jacobsohn K Kenfield SA et al September 2022 Systematic review of the impact of a plant based diet on prostate cancer incidence and outcomes Prostate Cancer and Prostatic Diseases 25 3 444 452 doi 10 1097 JU 0000000000002518 04 PMID 35790788 S2CID 248030075 a b Scher amp Eastham 2022 No Cancer Diagnosis Milk and Health American College of Cardiology Retrieved 2021 02 21 Willett WC Ludwig DS February 2020 Milk and Health The New England Journal of Medicine 382 7 644 654 doi 10 1056 NEJMra1903547 PMID 32053300 S2CID 211099544 Sargsyan A Dubasi HB July 2021 Milk Consumption and Prostate Cancer A Systematic Review The World Journal of Men s Health 39 3 419 428 doi 10 5534 wjmh 200051 PMC 8255404 PMID 32777868 Lopez Plaza B Bermejo LM Santurino C Cavero Redondo I Alvarez Bueno C Gomez Candela C May 2019 Milk and Dairy Product Consumption and Prostate Cancer Risk and Mortality An Overview of Systematic Reviews and Meta analyses Advances in Nutrition 10 suppl 2 S212 S223 doi 10 1093 advances nmz014 PMC 6518142 PMID 31089741 Wigle DT Turner MC Gomes J Parent ME March 2008 Role of hormonal and other factors in human prostate cancer Journal of Toxicology and Environmental Health Part B Critical Reviews 11 3 4 242 259 doi 10 1080 10937400701873548 PMID 18368555 S2CID 24489849 a b c d e Masko EM Allott EH Freedland SJ May 2013 The relationship between nutrition and prostate cancer is more always better European Urology 63 5 810 820 doi 10 1016 j eururo 2012 11 012 PMC 3597758 PMID 23219353 Thompson AK Shaw DI Minihane AM Williams CM December 2008 Trans fatty acids and cancer the evidence reviewed Nutrition Research Reviews 21 2 174 188 doi 10 1017 S0954422408110964 PMID 19087370 Heinze VM Actis AB February 2012 Dietary conjugated linoleic acid and long chain n 3 fatty acids in mammary and prostate cancer protection a review International Journal of Food Sciences and Nutrition 63 1 66 78 doi 10 3109 09637486 2011 598849 PMID 21762028 S2CID 21614046 Datta M Schwartz GG 2012 Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer a critical review The Oncologist 17 9 1171 1179 doi 10 1634 theoncologist 2012 0051 PMC 3448410 PMID 22836449 Szymanski KM Wheeler DC Mucci LA November 2010 Fish consumption and prostate cancer risk a review and meta analysis The American Journal of Clinical Nutrition 92 5 1223 1233 doi 10 3945 ajcn 2010 29530 PMID 20844069 American Dietetic Association June 2003 Position of the American Dietetic Association and Dietitians of Canada Vegetarian diets Journal of the American Dietetic Association 103 6 748 765 doi 10 1053 jada 2003 50142 PMID 12778049 World Cancer Research Fund American Institute for Cancer 2007 Food nutrition physical activity and the prevention of cancer a global perspective PDF Washington D C American Institute for Cancer Research p 76 ISBN 978 0 9722522 2 5 Archived from the original PDF on 2013 05 23 Rowles JL Ranard KM Applegate CC Jeon S An R Erdman JW September 2018 Processed and raw tomato consumption and risk of prostate cancer a systematic review and dose response meta analysis Prostate Cancer and Prostatic Diseases 21 3 319 336 doi 10 1038 s41391 017 0005 x PMID 29317772 S2CID 3306182 a b American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention PDF American Cancer Society Archived PDF from the original on 2012 06 25 Torti DC Matheson GO 2004 05 01 Exercise and prostate cancer Sports Medicine 34 6 363 369 doi 10 2165 00007256 200434060 00003 PMID 15157121 S2CID 43085964 Jacobs EJ Rodriguez C Mondul AM Connell CJ Henley SJ Calle EE Thun MJ July 2005 A large cohort study of aspirin and other nonsteroidal anti inflammatory drugs and prostate cancer incidence Journal of the National Cancer Institute 97 13 975 980 doi 10 1093 jnci dji173 PMID 15998950 Shannon J Tewoderos S Garzotto M Beer TM Derenick R Palma A Farris PE August 2005 Statins and prostate cancer risk a case control study American Journal of Epidemiology 162 4 318 325 doi 10 1093 aje kwi203 PMID 16014776 Dennis LK Lynch CF Torner JC July 2002 Epidemiologic association between prostatitis and prostate cancer Urology 60 1 78 83 doi 10 1016 S0090 4295 02 01637 0 PMID 12100928 Heidegger I Borena W Pichler R May 2015 The role of human papilloma virus in urological malignancies Anticancer Research 35 5 2513 2519 PMID 25964524 Cai T Di Vico T Durante J Tognarelli A Bartoletti R December 2018 Human papilloma virus and genitourinary cancers a narrative review Minerva Urologica e Nefrologica 70 6 579 587 doi 10 23736 S0393 2249 18 03141 7 PMID 30160386 S2CID 52118310 Prostate Cancer Johns Hopkins Brady Urological Institute www hopkinsmedicine org Retrieved 2022 04 28 Rider JR Wilson KM Sinnott JA Kelly RS Mucci LA Giovannucci EL December 2016 Ejaculation Frequency and Risk of Prostate Cancer Updated Results with an Additional Decade of Follow up European Urology 70 6 974 982 doi 10 1016 j eururo 2016 03 027 PMC 5040619 PMID 27033442 Aboul Enein BH Bernstein J Ross MW July 2016 Evidence for Masturbation and Prostate Cancer Risk Do We Have a Verdict Sexual Medicine Reviews 4 3 229 234 doi 10 1016 j sxmr 2016 02 006 PMID 27871956 A comprehensive cancer control program for BC Retrieved 2 November 2021 Aumuller G 1979 Prostate Gland and Seminal Vesicles Berlin Heidelberg Springer Verlag Moore KL Chubb D 1999 Clinically Oriented Anatomy Baltimore Maryland Lippincott Williams amp Wilkins ISBN 978 0 683 06132 1 Steive H 1930 Mannliche Genitalorgane Handbuch der mikroskopischen Anatomie des Menschen Vol VII Part 2 Berlin Springer pp 1 399 Collins MA Terris MK 2021 10 25 Talavera F Noble MJ eds Transurethral Resection of the Prostate Overview Treatment amp Management Post Procedure Medscape McNeal JE 1984 Anatomy of the prostate and morphogenesis of BPH Progress in Clinical and Biological Research 145 27 53 PMID 6201879 Muruve MA 2020 06 11 Gest TR ed Prostate Anatomy Overview Gross Anatomy Microscopic Anatomy Medscape Singh O Bolla SR 2022 Anatomy Abdomen and Pelvis Prostate StatPearls Treasure Island FL StatPearls Publishing PMID 31082031 Retrieved 2022 04 28 Schenkman NS Manger JP 2020 06 11 Gest TR ed Male Urethra Anatomy Overview Gross Anatomy Microscopic Anatomy Medscape Pisipati S Ali A Mandalapu RS Haines Iii GK Singhal P Reddy BN et al October 2014 Newer concepts in neural anatomy and neurovascular preservation in robotic radical prostatectomy Indian Journal of Urology 30 4 399 409 doi 10 4103 0970 1591 142064 PMC 4220380 PMID 25378822 Oh WK Hurwitz M D Amico AV Richie JP Kantoff PW 2003 Biology of Prostate Cancer Holland Frei Cancer Medicine 6th ed Reissigl A Pointner J Strasser H Ennemoser O Klocker H Bartsch G February 1997 Frequency and clinical significance of transition zone cancer in prostate cancer screening The Prostate 30 2 130 135 doi 10 1002 SICI 1097 0045 19970201 30 2 lt 130 AID PROS8 gt 3 0 CO 2 S PMID 9051151 S2CID 24142928 Androgens Function Measurement and Related Disorders Cleveland Clinic Retrieved 2022 04 28 a b Prostate Cancer Symptoms Diagnosis amp Treatment Cleveland Clinic Retrieved 2022 04 28 Prostate Tumor an overview ScienceDirect Topics www sciencedirect com Retrieved 2022 04 28 Zhou M January 2018 High grade prostatic intraepithelial neoplasia PIN like carcinoma ductal carcinoma and intraductal carcinoma of the prostate Modern Pathology 31 S1 S71 S79 doi 10 1038 modpathol 2017 138 PMID 29297491 S2CID 13649812 Brosman SA Goluboff ET Talavera F Theodorescu D 2021 10 04 Kim ED ed Precancerous Lesions of the Prostate Overview PIN and ASAP Rates Diagnostic Significance Advanced Prostate Cancer Symptoms Diagnosis amp Treatment Urology Care Foundation www urologyhealth org Retrieved 2022 04 28 Martin TA Ye L Sanders AJ Lane J Jiang WG 2013 Cancer Invasion and Metastasis Molecular and Cellular Perspective Landes Bioscience Leslie SW Soon Sutton TL Sajjad H Siref LE 2022 Prostate Cancer StatPearls Treasure Island FL StatPearls Publishing PMID 29261872 Retrieved 2022 04 28 Male Genitals Prostate Neoplasms Pathology study images University of Virginia School of Medicine Archived from the original on 2011 07 20 Retrieved 2011 04 28 There are many connections between the prostatic venous plexus and the vertebral veins The veins forming the prostatic plexus do not contain valves and it is thought that straining to urinate causes prostatic venous blood to flow in a reverse direction and enter the vertebral veins carrying malignant cells to the vertebral column a b Costello LC Franklin RB May 2006 The clinical relevance of the metabolism of prostate cancer zinc and tumor suppression connecting the dots Molecular Cancer 5 17 doi 10 1186 1476 4598 5 17 PMC 1481516 PMID 16700911 Vickram S Rohini K Srinivasan S Nancy Veenakumari D Archana K Anbarasu K et al February 2021 Role of Zinc Zn in Human Reproduction A Journey from Initial Spermatogenesis to Childbirth International Journal of Molecular Sciences 22 4 2188 doi 10 3390 ijms22042188 PMC 7926410 PMID 33671837 Costello LC Franklin RB June 1998 Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer The Prostate 35 4 285 296 doi 10 1002 sici 1097 0045 19980601 35 4 lt 285 aid pros8 gt 3 0 co 2 f PMID 9609552 S2CID 21084346 Franklin RB Feng P Milon B Desouki MM Singh KK Kajdacsy Balla A et al September 2005 hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer Molecular Cancer 4 32 doi 10 1186 1476 4598 4 32 PMC 1243239 PMID 16153295 Uzzo RG Leavis P Hatch W Gabai VL Dulin N Zvartau N Kolenko VM November 2002 Zinc inhibits nuclear factor kappa B activation and sensitizes prostate cancer cells to cytotoxic agents Clinical Cancer Research 8 11 3579 3583 PMID 12429649 Scientists Discover Anti Cancer Mechanism that Arrests Early Prostate Cancer August 4 2005 Archived from the original on May 19 2008 Sharma A Yeow WS Ertel A Coleman I Clegg N Thangavel C et al December 2010 The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression The Journal of Clinical Investigation 120 12 4478 4492 doi 10 1172 JCI44239 PMC 2993601 PMID 21099110 Ruela de Sousa RR Hoekstra E Hoogland AM Souza Queiroz KC Peppelenbosch MP Stubbs AP et al April 2016 Low Molecular Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential European Urology 69 4 710 719 doi 10 1016 j eururo 2015 06 040 PMID 26159288 Leav I Plescia J Goel HL Li J Jiang Z Cohen RJ et al January 2010 Cytoprotective mitochondrial chaperone TRAP 1 as a novel molecular target in localized and metastatic prostate cancer The American Journal of Pathology 176 1 393 401 doi 10 2353 ajpath 2010 090521 PMC 2797899 PMID 19948822 Zha J Huang YF September 2009 TGF beta Smad in prostate cancer an update Zhonghua Nan Ke Xue National Journal of Andrology in Chinese 15 9 840 843 PMID 19947572 Watanabe S Miyata Y Kanda S Iwata T Hayashi T Kanetake H Sakai H May 2010 Expression of X linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo adjuvant hormonal therapy Journal of Cancer Research and Clinical Oncology 136 5 787 793 doi 10 1007 s00432 009 0718 x PMID 19946707 S2CID 34855148 Senapati S Rachagani S Chaudhary K Johansson SL Singh RK Batra SK March 2010 Overexpression of macrophage inhibitory cytokine 1 induces metastasis of human prostate cancer cells through the FAK RhoA signaling pathway Oncogene 29 9 1293 1302 doi 10 1038 onc 2009 420 PMC 2896817 PMID 19946339 Narizhneva NV Tararova ND Ryabokon P Shyshynova I Prokvolit A Komarov PG et al December 2009 Small molecule screening reveals a transcription independent pro survival function of androgen receptor in castration resistant prostate cancer Cell Cycle 8 24 4155 4167 doi 10 4161 cc 8 24 10316 PMC 2896895 PMID 19946220 Yao V Berkman CE Choi JK O Keefe DS Bacich DJ February 2010 Expression of prostate specific membrane antigen PSMA increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non polyglutamated folate folic acid The Prostate 70 3 305 316 doi 10 1002 pros 21065 PMID 19830782 S2CID 21518526 a b Alberts AR Schoots IG Roobol MJ June 2015 Prostate specific antigen based prostate cancer screening Past and future International Journal of Urology 22 6 524 532 doi 10 1111 iju 12750 PMID 25847604 S2CID 7525080 a b Rendon RA Mason RJ Marzouk K Finelli A Saad F So A et al October 2017 Canadian Urological Association recommendations on prostate cancer screening and early diagnosis Canadian Urological Association Journal 11 10 298 309 doi 10 5489 cuaj 4888 PMC 5659858 PMID 29381452 Home Page USPSTF Draft Prostate Screening Recommendations USPSTF Draft Prostate Screening Recommendations Archived from the original on 2 March 2018 Retrieved 2 March 2018 Mulhem E Fulbright N Duncan N October 2015 Prostate Cancer Screening American Family Physician 92 8 683 688 PMID 26554408 Prostate Cancer Screening Archived 2017 09 07 at the Wayback Machine CDC updated April 6 2010 Qaseem A Barry MJ Denberg TD Owens DK Shekelle P May 2013 Screening for prostate cancer a guidance statement from the Clinical Guidelines Committee of the American College of Physicians Annals of Internal Medicine 158 10 761 769 doi 10 7326 0003 4819 158 10 201305210 00633 PMID 23567643 Basch E Oliver TK Vickers A Thompson I Kantoff P Parnes H et al August 2012 Screening for prostate cancer with prostate specific antigen testing American Society of Clinical Oncology Provisional Clinical Opinion Journal of Clinical Oncology 30 24 3020 3025 doi 10 1200 JCO 2012 43 3441 PMC 3776923 PMID 22802323 Carter HB September 2013 American Urological Association AUA guideline on prostate cancer detection process and rationale BJU International 112 5 543 547 doi 10 1111 bju 12318 PMID 23924423 S2CID 19703425 Early Detection of Prostate Cancer AUA Guidelines American Urological Association 2013 Archived from the original on 7 May 2013 Retrieved 10 May 2013 Cancer Screening Guidelines Detecting Cancer Early Archived from the original on 2011 06 13 Retrieved 2011 06 16 American Cancer Society American Cancer Society Guidelines for the early detection of cancer Cited September 2011 Prostate Cancer and the Digital Rectal Exam WebMD Retrieved 2022 04 28 Cystoscopy Purpose Procedure and Preparation Healthline 2015 10 19 Retrieved 2022 04 28 Scher amp Eastham 2022 Prostate Biopsy El Shafei AR Jones JS 2021 10 04 Kim ED ed Prostate Biopsy Practice Essentials Background Indications and Contraindications Medscape Drost FH Osses D Nieboer D Bangma CH Steyerberg EW Roobol MJ Schoots IG January 2020 Prostate Magnetic Resonance Imaging with or Without Magnetic Resonance Imaging targeted Biopsy and Systematic Biopsy for Detecting Prostate Cancer A Cochrane Systematic Review and Meta analysis European Urology 77 1 78 94 doi 10 1016 j eururo 2019 06 023 PMID 31326219 S2CID 198131275 Transrectal Ultrasonography an overview ScienceDirect Topics www sciencedirect com Retrieved 2022 04 28 Ebeid AI Elshamy AS 2018 09 01 Hypoechoic versus hypervascular lesion in the diagnosis of prostatic carcinoma African Journal of Urology 24 3 169 174 doi 10 1016 j afju 2018 01 004 ISSN 1110 5704 S2CID 81718491 Yaghi MD Kehinde EO 2015 Oral antibiotics in trans rectal prostate biopsy and its efficacy to reduce infectious complications Systematic review Urology Annals 7 4 417 427 doi 10 4103 0974 7796 164860 PMC 4660689 PMID 26538868 Zani EL Clark OA Rodrigues Netto N May 2011 Antibiotic prophylaxis for transrectal prostate biopsy The Cochrane Database of Systematic Reviews 5 CD006576 doi 10 1002 14651858 CD006576 pub2 PMID 21563156 Essink Bot ML de Koning HJ Nijs HG Kirkels WJ van der Maas PJ Schroder FH June 1998 Short term effects of population based screening for prostate cancer on health related quality of life Journal of the National Cancer Institute 90 12 925 931 doi 10 1093 jnci 90 12 925 PMID 9637143 a b c d Scher amp Eastham 2022 Pathology Chuang AY DeMarzo AM Veltri RW Sharma RB Bieberich CJ Epstein JI August 2007 Immunohistochemical differentiation of high grade prostate carcinoma from urothelial carcinoma The American Journal of Surgical Pathology 31 8 1246 1255 doi 10 1097 PAS 0b013e31802f5d33 PMID 17667550 S2CID 11535862 References for pie chart are located in table in the article Histopathologic diagnosis of prostate cancer Incidences spelling generally include cases where the pattern is found admixed with usual acinar adenocarcinoma a b Prostate Cancer Staging American Cancer Society 8 October 2021 Retrieved 14 May 2023 a b c Scher amp Eastham 2022 Table 87 1 TNM Classification Prostate cancer diagnosis and management NICE guideline NG131 National Institute for Health and Care Excellence NICE Retrieved 2022 10 03 EAU Guidelines on Prostate Cancer DIAGNOSTIC EVALUATION Uroweb European Association of Urology March 2023 Retrieved 15 May 2023 National Comprehensive Cancer Network Prostate 2012 NCCN Clinical Practice Guidelines in Oncology nccn org Archived from the original on 9 November 2012 Retrieved 15 November 2012 Thompson I Thrasher JB Aus G Burnett AL Canby Hagino ED Cookson MS et al June 2007 Guideline for the management of clinically localized prostate cancer 2007 update The Journal of Urology 177 6 2106 2131 doi 10 1016 j juro 2007 03 003 PMID 17509297 American Society of Clinical Oncology April 2013 Five things physicians and patients should question PDF The Journal of the Oklahoma State Medical Association 106 4 150 151 PMID 23795527 Archived from the original PDF on 2012 07 31 Makarov DV Desai RA Yu JB Sharma R Abraham N Albertsen PC et al January 2012 The population level prevalence and correlates of appropriate and inappropriate imaging to stage incident prostate cancer in the medicare population The Journal of Urology 187 1 97 102 doi 10 1016 j juro 2011 09 042 PMID 22088337 Macedo F Ladeira K Pinho F Saraiva N Bonito N Pinto L Goncalves F March 2017 Bone Metastases An Overview Oncology Reviews 11 1 321 doi 10 4081 oncol 2017 321 PMC 5444408 PMID 28584570 Hofman MS Lawrentschuk N Francis RJ Tang C Vela I Thomas P et al April 2020 Prostate specific membrane antigen PET CT in patients with high risk prostate cancer before curative intent surgery or radiotherapy proPSMA a prospective randomised multicentre study Lancet 395 10231 1208 1216 doi 10 1016 S0140 6736 20 30314 7 PMID 32209449 S2CID 214609500 FDA approves novel PSMA PET imaging product for prostate cancer Urology Times Retrieved 2023 01 04 PSMA Radiopharmaceutical Effective against Prostate Cancer National Cancer Institute National Institutes of Health 29 June 2021 Fallahi Babak Khademi Niloufar Karamzade Ziarati Najme Fard Esfahani Armaghan Emami Ardekani Alireza Farzanefar Saeed Eftekhari Mohammad Beiki Davood February 2021 99mTc PSMA SPECT CT Versus 68Ga PSMA PET CT in the Evaluation of Metastatic Prostate Cancer Clinical Nuclear Medicine 46 2 e68 e74 doi 10 1097 RLU 0000000000003410 ISSN 1536 0229 PMID 33234922 S2CID 227168658 Harsini Sara Fallahi Babak Karamzade Ziarati Najme Razi Ali Amini Erfan Emami Ardekani Alireza Fard Esfahani Armaghan Kardoust Parizi Mehdi Farzanehfar Saeed Beiki Davood 2021 A Prospective Study on 68Ga PSMA PET CT Imaging in Newly Diagnosed Intermediate and High Risk Prostate Cancer Asia Oceania Journal of Nuclear Medicine amp Biology 9 2 101 110 doi 10 22038 AOJNMB 2020 52375 1358 ISSN 2322 5718 PMC 8255520 PMID 34250139 a b c d Filson CP Marks LS Litwin MS 8 May 2015 Expectant management for men with early stage prostate cancer CA 65 4 265 282 doi 10 3322 caac 21278 PMID 25958817 S2CID 36057004 Jayadevappa R Chhatre S Wong YN Wittink MN Cook R Morales KH et al May 2017 Comparative effectiveness of prostate cancer treatments for patient centered outcomes A systematic review and meta analysis PRISMA Compliant Medicine 96 18 e6790 doi 10 1097 MD 0000000000006790 PMC 5419922 PMID 28471976 Lu Yao GL Albertsen PC Moore DF Shih W Lin Y DiPaola RS et al September 2009 Outcomes of localized prostate cancer following conservative management JAMA 302 11 1202 1209 doi 10 1001 jama 2009 1348 PMC 2822438 PMID 19755699 Mongiat Artus P Peyromaure M Richaud P Droz JP Rainfray M Jeandel C et al December 2009 Recommendations for the treatment of prostate cancer in the elderly man A study by the oncology committee of the French association of urology Progres en Urologie in French 19 11 810 817 doi 10 1016 j purol 2009 02 008 PMID 19945664 Picard JC Golshayan AR Marshall DT Opfermann KJ Keane TE November 2009 The multi disciplinary management of high risk prostate cancer Urologic Oncology 30 1 3 15 doi 10 1016 j urolonc 2009 09 002 PMID 19945310 a b Mohan R Schellhammer PF August 2011 Treatment options for localized prostate cancer American Family Physician 84 4 413 420 PMID 21842788 Rawla P April 2019 Epidemiology of Prostate Cancer World Journal of Oncology 10 2 63 89 doi 10 14740 wjon1191 PMC 6497009 PMID 31068988 Fitzpatrick JM March 2008 Management of localized prostate cancer in senior adults the crucial role of comorbidity BJU International 101 Suppl 2 Suppl 2 16 22 doi 10 1111 j 1464 410X 2007 07487 x PMID 18307688 S2CID 205538470 Evidence Based Cancer Guidelines Oncology Drug Compendium Oncology Continuing Medical Education NCCN Retrieved 2011 08 29 Cooper GM 2000 The Development and Causes of Cancer The Cell A Molecular Approach 2nd ed Active Surveillance for the Management of Localized Prostate Cancer Cancer Care Ontario Archived from the original on 2020 04 10 Ellis SD Hwang S Morrow E Kimminau KS Goonan K Petty L et al May 2021 Perceived barriers to the adoption of active surveillance in low risk prostate cancer a qualitative analysis of community and academic urologists BMC Cancer 21 1 649 doi 10 1186 s12885 021 08386 3 PMC 8165996 PMID 34058998 Cancer www who int Retrieved 2022 04 28 Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer Cancer gov 2011 04 19 Archived from the original on 2011 05 03 Retrieved 2011 08 29 a b c d Vernooij RW Lancee M Cleves A Dahm P Bangma CH Aben KK June 2020 Radical prostatectomy versus deferred treatment for localised prostate cancer The Cochrane Database of Systematic Reviews 2020 6 CD006590 doi 10 1002 14651858 CD006590 pub3 PMC 7270852 PMID 32495338 Sartor O de Bono JS February 2018 Metastatic Prostate Cancer The New England Journal of Medicine 378 7 645 657 doi 10 1056 NEJMra1701695 PMID 29412780 Prostate cancer Diagnosis and treatment Mayo Clinic www mayoclinic org Retrieved 2022 04 28 Dhondt B De Bleser E Claeys T Buelens S Lumen N Vandesompele J et al December 2019 Discovery and validation of a serum microRNA signature to characterize oligo and polymetastatic prostate cancer not ready for prime time World Journal of Urology 37 12 2557 2564 doi 10 1007 s00345 018 2609 8 PMID 30578441 S2CID 58594673 Hormone Therapy for Breast Cancer Breast Cancer Treatment www cancer org Retrieved 2022 04 28 Hammerstrom AE Cauley DH Atkinson BJ Sharma P August 2011 Cancer immunotherapy sipuleucel T and beyond Pharmacotherapy 31 8 813 828 doi 10 1592 phco 31 8 813 PMC 4159742 PMID 21923608 Prostate Cancer Radical Prostatectomy WebMD Retrieved 10 May 2020 Radical Prostatectomy for Prostate Cancer Memorial Sloan Kettering Cancer Center www mskcc org Retrieved 2022 05 25 Mouraviev V Evans B Polascik TJ 2006 Salvage prostate cryoablation after primary interstitial brachytherapy failure a feasible approach Prostate Cancer and Prostatic Diseases 9 1 99 101 doi 10 1038 sj pcan 4500853 PMID 16314889 Wallis CJ Mahar AL Choo R Herschorn S Kodama RT Shah PS et al March 2016 Second malignancies after radiotherapy for prostate cancer systematic review and meta analysis BMJ 352 i851 doi 10 1136 bmj i851 PMC 4775870 PMID 26936410 Wallis CJ Glaser A Hu JC Huland H Lawrentschuk N Moon D et al January 2018 Survival and Complications Following Surgery and Radiation for Localized Prostate Cancer An International Collaborative Review PDF European Urology 73 1 11 20 doi 10 1016 j eururo 2017 05 055 PMID 28610779 Hong H Zhang Y Sun J Cai W June 2010 Positron emission tomography imaging of prostate cancer Amino Acids 39 1 11 27 doi 10 1007 s00726 009 0394 9 PMC 2883014 PMID 19946787 Peyromaure M Valeri A Rebillard X Beuzeboc P Richaud P Soulie M Salomon L December 2009 Characteristics of prostate cancer in men less than 50 year old Progres en Urologie in French 19 11 803 809 doi 10 1016 j purol 2009 04 010 PMID 19945663 Castrate resistant prostate cancer In NCI Dictionary of Cancer Terms National Cancer Institute US National Institutes of Health 2019 Retrieved 17 September 2019 Treatments for castrate resistant prostate cancer Canadian Cancer Society 2019 Retrieved 17 September 2019 Tran K McGill S Treatment Sequences of Androgen Receptor Targeted Agents for Prostate Cancer Internet Ottawa ON Canadian Agency for Drugs and Technologies in Health 2021 March Available from https www ncbi nlm nih gov books NBK571920 Seruga B Ocana A Tannock IF January 2011 Drug resistance in metastatic castration resistant prostate cancer Nature Reviews Clinical Oncology 8 1 12 23 doi 10 1038 nrclinonc 2010 136 PMID 20859283 S2CID 24512148 Clarke NW 2005 Docetaxel for the Treatment of Hormone Refractory Prostate Cancer PDF Archived from the original PDF on 2012 07 12 Prostate cancer hormone refractory docetaxel National Institute for Health and Clinical Excellence 2010 12 10 Archived from the original on 2012 02 02 Retrieved 2011 07 04 de Bono JS Oudard S Ozguroglu M Hansen S Machiels JP Kocak I et al October 2010 Prednisone plus cabazitaxel or mitoxantrone for metastatic castration resistant prostate cancer progressing after docetaxel treatment a randomised open label trial Lancet 376 9747 1147 1154 doi 10 1016 S0140 6736 10 61389 X PMID 20888992 S2CID 4791847 Avastin Thalomid Taxotere and Prednisone Effective for Men with Hormone Refractory Prostate Cancer March 2010 Archived from the original on 15 June 2010 Retrieved 10 May 2010 Kantoff PW Higano CS Shore ND Berger ER Small EJ Penson DF et al July 2010 Sipuleucel T immunotherapy for castration resistant prostate cancer The New England Journal of Medicine 363 5 411 422 doi 10 1056 NEJMoa1001294 PMID 20818862 S2CID 12168204 FDA approves Zytiga for late stage prostate cancer U S Food and Drug Administration 2011 04 28 Archived from the original on 2013 09 22 a b c FDA approves new treatment for a type of late stage prostate cancer Press release Food and Drug Administration 2012 08 31 Archived from the original on 2013 10 02 a b c Azvolinsky A September 4 2012 FDA Approves Enzalutamide Xtandi for Late Stage Prostate Cancer CancerNetwork Archived from the original on September 13 2012 Qin J Liu X Laffin B Chen X Choy G Jeter CR et al May 2012 The PSA lo prostate cancer cell population harbors self renewing long term tumor propagating cells that resist castration Cell Stem Cell 10 5 556 569 doi 10 1016 j stem 2012 03 009 PMC 3348510 PMID 22560078 Maitland NJ Collins AT June 2008 Prostate cancer stem cells a new target for therapy Journal of Clinical Oncology 26 17 2862 2870 doi 10 1200 JCO 2007 15 1472 PMID 18539965 Attard G Richards J de Bono JS April 2011 New strategies in metastatic prostate cancer targeting the androgen receptor signaling pathway Clinical Cancer Research 17 7 1649 1657 doi 10 1158 1078 0432 CCR 10 0567 PMC 3513706 PMID 21372223 Rane JK Pellacani D Maitland NJ October 2012 Advanced prostate cancer a case for adjuvant differentiation therapy Nature Reviews Urology 9 10 595 602 doi 10 1038 nrurol 2012 157 PMID 22890299 S2CID 43634798 a b Jakob T Tesfamariam YM Macherey S Kuhr K Adams A Monsef I et al Cochrane Urology Group December 2020 Bisphosphonates or RANK ligand inhibitors for men with prostate cancer and bone metastases a network meta analysis The Cochrane Database of Systematic Reviews 2020 12 CD013020 doi 10 1002 14651858 CD013020 pub2 PMC 8095056 PMID 33270906 Radical prostatectomy MedlinePlus Medical Encyclopedia medlineplus gov Retrieved 2022 04 28 Khera M Miles BJ Cornell RJ Colen JS 2021 10 16 Schwartz BF ed Simple Prostatectomy Overview Preparation Technique Medscape a b Surgery for Prostate Cancer www cancer org Retrieved 2020 03 30 a b Ilic D Evans SM Allan CA Jung JH Murphy D Frydenberg M September 2017 Laparoscopic and robotic assisted versus open radical prostatectomy for the treatment of localised prostate cancer The Cochrane Database of Systematic Reviews 2017 9 CD009625 doi 10 1002 14651858 cd009625 pub2 PMC 6486168 PMID 28895658 a b Tan N Margolis DJ McClure TD Thomas A Finley DS Reiter RE et al August 2012 Radical prostatectomy value of prostate MRI in surgical planning Abdominal Imaging 37 4 664 674 doi 10 1007 s00261 011 9805 y PMID 21993567 S2CID 20471235 Scheltema MJ Tay KJ Postema AW de Bruin DM Feller J Futterer JJ et al May 2017 Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy report from a Delphi consensus project World Journal of Urology 35 5 695 701 doi 10 1007 s00345 016 1932 1 OCLC 1188365278 PMC 5397427 PMID 27637908 Wang T Zhou J Tian S Wang Y Patel P Jani AB et al March 2020 A planning study of focal dose escalations to multiparametric MRI defined dominant intraprostatic lesions in prostate proton radiation therapy The British Journal of Radiology 93 1107 20190845 doi 10 1259 bjr 20190845 PMC 7066949 PMID 31904261 Heavey S Haider A Sridhar A Pye H Shaw G Freeman A Whitaker H October 2019 Use of Magnetic Resonance Imaging and Biopsy Data to Guide Sampling Procedures for Prostate Cancer Biobanking Journal of Visualized Experiments 152 doi 10 3791 60216 PMID 31657791 Heavey S Costa H Pye H Burt EC Jenkinson S Lewis GR et al May 2019 PEOPLE PatiEnt prOstate samPLes for rEsearch a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens The Prostate 79 7 768 777 doi 10 1002 pros 23782 PMC 6618051 PMID 30807665 Continence management following prostate surgery Continence Foundation of Australia Archived from the original on 2020 04 10 Prostate Cancer and Urinary Incontinence WebMD Retrieved 2022 04 28 Incontinence After Prostate Cancer Surgery Cleveland Clinic Retrieved 2022 04 28 Singla N Singla AK March 2014 Post prostatectomy incontinence Etiology evaluation and management Turkish Journal of Urology 40 1 1 8 doi 10 5152 tud 2014 222014 PMC 4548645 PMID 26328137 Sajadi KP Terris MK 2021 11 29 Talavera F ed Artificial Urinary Sphincter Placement Practice Essentials History of the Procedure Problem Medscape EAU Guidelines on Urinary Incontinence in Adults PDF European Association of Urology 2018 Archived from the original PDF on 2020 02 08 Retrieved 2020 04 01 Erectile Dysfunction After Prostate Cancer www hopkinsmedicine org 19 November 2019 Retrieved 2020 04 01 Parahoo K McDonough S McCaughan E Noyes J Semple C Halstead EJ et al December 2013 Parahoo K ed Psychosocial interventions for men with prostate cancer The Cochrane Database of Systematic Reviews 12 CD008529 doi 10 1002 14651858 CD008529 pub3 PMID 24368598 Vartolomei L Shariat SF Vartolomei MD September 2018 Psychotherapeutic Interventions Targeting Prostate Cancer Patients A Systematic Review of the Literature European Urology Oncology 1 4 283 291 doi 10 1016 j euo 2018 04 011 PMID 31100249 S2CID 81502256 Nnate DA Anyachukwu CC Igwe SE Abaraogu UO October 2021 Mindfulness based interventions for psychological wellbeing and quality of life in men with prostate cancer A systematic review and meta analysis Psycho Oncology 30 10 1680 1690 doi 10 1002 pon 5749 PMID 34139035 S2CID 235470939 Cancer of the Prostate Cancer Stat Facts seer cancer gov Archived from the original on 18 March 2017 Retrieved 11 April 2017 Wakai K February 2005 Descriptive epidemiology of prostate cancer in Japan and Western countries Nihon Rinsho Japanese Journal of Clinical Medicine in Japanese 63 2 207 212 PMID 15714967 Jaubert de Beaujeu M Chavrier Y January 1976 Deformations of the anterior thoracic wall author s transl Annales de Chirurgie Thoracique et Cardio Vasculaire in French 15 1 1 6 PMID 1259345 Hsing AW Tsao L Devesa SS January 2000 International trends and patterns of prostate cancer incidence and mortality International Journal of Cancer 85 1 60 67 doi 10 1002 SICI 1097 0215 20000101 85 1 lt 60 AID IJC11 gt 3 0 CO 2 B PMID 10585584 S2CID 21911559 Osegbe DN April 1997 Prostate cancer in Nigerians facts and nonfacts The Journal of Urology 157 4 1340 1343 doi 10 1016 S0022 5347 01 64966 8 PMID 9120935 Bello JO May 2017 Predictors of survival outcomes in native sub Saharan black men newly diagnosed with metastatic prostate cancer BMC Urology 17 1 39 doi 10 1186 s12894 017 0228 0 PMC 5450414 PMID 28558685 Nelson WG Antonarakis ES Carter HB De Marzo AM DeWeese TL 2020 01 01 81 Prostate Cancer In Niederhuber JE Armitage JO Kastan MB Doroshow JH eds Abeloff s Clinical Oncology Sixth ed Philadelphia Elsevier pp 1401 1432 e7 ISBN 978 0 323 47674 4 Di Blasio CJ Rhee AC Cho D Scardino PT Kattan MW October 2003 Predicting clinical end points treatment nomograms in prostate cancer Seminars in Oncology 30 5 567 586 doi 10 1016 S0093 7754 03 00351 8 PMID 14571407 Lovf M Zhao S Axcrona U Johannessen B Bakken AC Carm KT et al March 2019 Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity European Urology 75 3 498 505 doi 10 1016 j eururo 2018 08 009 PMID 30181068 S2CID 52156954 prostate predict nhs uk Devos G Joniau S July 2020 PREDICT Prostate a useful tool in men with low and intermediate risk prostate cancer who are hesitant between conservative management and active treatment BMC Medicine 18 1 213 doi 10 1186 s12916 020 01681 z PMC 7364577 PMID 32669105 S2CID 220544109 Thurtle D Bratt O Stattin P Pharoah P Gnanapragasam V June 2020 Comparative performance and external validation of the multivariable PREDICT Prostate tool for non metastatic prostate cancer a study in 69 206 men from Prostate Cancer data Base Sweden PCBaSe BMC Medicine 18 1 139 doi 10 1186 s12916 020 01606 w PMC 7296776 PMID 32539712 S2CID 219691220 Thurtle DR Greenberg DC Lee LS Huang HH Pharoah PD Gnanapragasam VJ March 2019 Individual prognosis at diagnosis in nonmetastatic prostate cancer Development and external validation of the PREDICT Prostate multivariable model PLOS Medicine 16 3 e1002758 doi 10 1371 journal pmed 1002758 PMC 6413892 PMID 30860997 Thurtle DR Jenkins V Pharoah PD Gnanapragasam VJ October 2019 Understanding of prognosis in non metastatic prostate cancer a randomised comparative study of clinician estimates measured against the PREDICT prostate prognostic model British Journal of Cancer 121 8 715 718 doi 10 1038 s41416 019 0569 4 PMC 6889281 PMID 31523057 S2CID 202573988 Thurtle D Jenkins V Freeman A Pearson M Recchia G Tamer P et al November 2021 Clinical Impact of the Predict Prostate Risk Communication Tool in Men Newly Diagnosed with Nonmetastatic Prostate Cancer A Multicentre Randomised Controlled Trial PDF European Urology 80 5 661 669 doi 10 1016 j eururo 2021 08 001 PMID 34493413 S2CID 237440530 Endorsed resource Predict Prostate Prostate cancer Diagnosis and management Guidance NICE Hellerstedt BA Pienta KJ 2002 The current state of hormonal therapy for prostate cancer CA 52 3 154 179 doi 10 3322 canjclin 52 3 154 PMID 12018929 S2CID 25311034 Feldman BJ Feldman D October 2001 The development of androgen independent prostate cancer Nature Reviews Cancer 1 1 34 45 doi 10 1038 35094009 PMID 11900250 S2CID 205020623 Hernandez DJ Nielsen ME Han M Partin AW November 2007 Contemporary evaluation of the D amico risk classification of prostate cancer Urology 70 5 931 935 doi 10 1016 j urology 2007 08 055 PMID 18068450 Eifler JB Feng Z Lin BM Partin MT Humphreys EB Han M et al January 2013 An updated prostate cancer staging nomogram Partin tables based on cases from 2006 to 2011 BJU International 111 1 22 29 doi 10 1111 j 1464 410X 2012 11324 x PMC 3876476 PMID 22834909 Prostate Cancer Nomograms Memorial Sloan Kettering Cancer Center www mskcc org Retrieved 2022 04 28 CaPSURE net Home Page 2006 09 27 Archived from the original on 2006 09 27 Retrieved 2020 08 08 Cooperberg MR Pasta DJ Elkin EP Litwin MS Latini DM Du Chane J Carroll PR June 2005 The University of California San Francisco Cancer of the Prostate Risk Assessment score a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy The Journal of Urology 173 6 1938 1942 doi 10 1097 01 ju 0000158155 33890 e7 PMC 2948569 PMID 15879786 Cooperberg MR Freedland SJ Pasta DJ Elkin EP Presti JC Amling CL et al November 2006 Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy Cancer 107 10 2384 2391 doi 10 1002 cncr 22262 PMID 17039503 S2CID 17420454 May M Knoll N Siegsmund M Fahlenkamp D Vogler H Hoschke B Gralla O November 2007 Validity of the CAPRA score to predict biochemical recurrence free survival after radical prostatectomy Results from a european multicenter survey of 1 296 patients The Journal of Urology 178 5 1957 62 discussion 1962 doi 10 1016 j juro 2007 07 043 PMID 17868719 Zhao KH Hernandez DJ Han M Humphreys EB Mangold LA Partin AW August 2008 External validation of University of California San Francisco Cancer of the Prostate Risk Assessment score Urology 72 2 396 400 doi 10 1016 j urology 2007 11 165 PMID 18372031 Cooperberg MR Broering JM Carroll PR June 2009 Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis Journal of the National Cancer Institute 101 12 878 887 doi 10 1093 jnci djp122 PMC 2697208 PMID 19509351 New guidance regarding the diagnosis and risk stratification of patients with prostate cancer BJU International 129 3 304 305 March 2022 doi 10 1111 bju 15703 PMID 35297163 S2CID 247475696 Gnanapragasam VJ Lophatananon A Wright KA Muir KR Gavin A Greenberg DC August 2016 Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer A Prognostic Modelling Study PLOS Medicine 13 8 e1002063 doi 10 1371 journal pmed 1002063 PMC 4970710 PMID 27483464 Gnanapragasam VJ Bratt O Muir K Lee LS Huang HH Stattin P Lophatananon A February 2018 The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non metastatic prostate cancer a validation study BMC Medicine 16 1 31 doi 10 1186 s12916 018 1019 5 PMC 5831573 PMID a, wikipedia, wiki, book, books, library,

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