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Factors that increase the risk of prostate cancer include older age, family history and race. About 99% of cases occur after age 50. A first-degree relative with the disease increases the risk two- to three-fold. Other factors include a diet high in processed meat and red meat, while the risk from a high intake of milk products is inconclusive. An association with gonorrhea has been found, although no reason for this relationship has been identified. An increased risk is associated with the BRCA mutations. Diagnosis is by biopsy.Medical imaging may be done to assess whether metastasis is present.
Globally, it is the second-most common cancer. It is the fifth-leading cause of cancer-related death in men. In 2018, it was diagnosed in 1.2 million and caused 359,000 deaths. It was the most common cancer in males in 84 countries, occurring more commonly in the developed world. Rates have been increasing in the developing world. Detection increased significantly in the 1980s and 1990s in many areas due to increased PSA testing. One study reported prostate cancer in 30% to 70% of Russian and Japanese men over age 60 who had died of unrelated causes.
Signs and symptoms
A diagram of prostate cancer pressing on the urethra, which can cause symptoms
Early prostate cancer usually has no clear symptoms. 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) and dysuria (painful urination). One study found that about a third of diagnosed patients had one or more such symptoms.
Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. 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.
The primary risk factors are obesity, age, and family history. Obese men have been found to have a 34% greater death rate from prostate cancer than those with normal weight. Prostate cancer is uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes found prostate cancer in 30% of men in their 50s, and in 80% of men in their 70s.
Men with high blood pressure are more likely to develop prostate cancer. A small increase in risk is associated with lack of exercise. Elevated blood testosterone levels may increase risk.
Genetics may affect risk, as suggested by associations with race, family, and specific gene variants. Men who have a first-degree relative (father or brother) with prostate cancer have twice the risk of developing prostate cancer, and those with two first-degree relatives affected have a five-fold greater risk compared with men with no family history. This risk appears to be greater for men with an affected brother than for those with an affected father. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men. 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 40% of prostate cancer risk can be explained by inherited factors.
Two large genome-wide association studies linked single-nucleotide polymorphisms (SNPs) to prostate cancer in 2008. These studies identified several relevant SNPs. For example, individuals with TT allele pair at SNP rs10993994 were reported to be at 1.6 times higher risk than those with the CC allele pair. This SNP explains part of the increased risk faced by African-Americans. The C allele is much more prevalent in the latter; this SNP is located in the promoter region of the MSMB gene, thus affects the amount of MSMB protein synthesized and secreted by epithelial cells of the prostate.
Consuming fruits and vegetables has been found to be of little preventive benefit. Red meat and processed meat appear to have little effect. Some studies reported that higher meat consumption was associated with higher risk.
Papilloma virus has been proposed in several studies to have a potential role, but as of 2015, the evidence was inconclusive. A 2018 review suggested possible increased risk, but was still debatable.
US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.
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. The prostate can be divided into four anatomic spaces: peripheral, central, transitional, and anterior fibromuscular stroma. The peripheral space contains the posterior and lateral portions of the prostate, as well as the inferior portions of the prostate. The central space contains the superior portion of the prostate including the most proximal aspects of the urethra and bladder neck. The transitional space is located just anterior to the central space and includes urethra distal to the central gland urethra. The neurovascular bundles course along the posterolateral prostate surface and penetrate the prostatic capsule there as well.
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). 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, 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.
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.
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. 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). Although no proof establishes that PIN is a cancer precursor, it is closely associated with cancer. Over time, these cells multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor.
Prostate cancer is considered a malignant tumor because it can invade other areas of the body. This invasion is called metastasis. Prostate cancer most commonly metastasizes to the bones and lymph nodes, and may invade the rectum, bladder, and lower ureters after local progression. The route of metastasis to bone is thought to be venous, as the prostatic venous plexus draining the prostate connects with the vertebral veins.
The prostate is a zinc-accumulating, citrate-producing organ. Transport proteinZIP1 is responsible for the transport of zinc into prostate cells. One of zinc's important roles is to change the cell's metabolism to produce citrate, an important semen component. 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.
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. Strategies that transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits NF-?B pathways, is antiproliferative, and induces apoptosis in abnormal cells. Unfortunately, oral ingestion of zinc is ineffective since high concentrations of zinc into prostate cells is not possible without ZIP1.
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". 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.
RUNX2 is a transcription factor that prevents cancer cells from undergoing apoptosis, thereby contributing to cancer development.
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."
Several other 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. Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted in the urethra. Transrectal ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum, but the only test that can fully confirm the diagnosis of prostate cancer is a biopsy, the removal of small pieces of the prostate for microscopic examination.
On MRI, the central and transitional zones both have lower T2 signal than the peripheral zone. Since the central and transitional zones cannot be distinguished from each other, they can be best described as the central gland on MRI. Thus, the peripheral gland has a higher signal on T2WI than the central gland. In the peripheral gland, prostate cancer appears as a low-intensity lesion. However, in the central gland, low-intensity lesions cannot be distinguished from the low-intensity central gland. Diffusion restriction is instrumental in identifying and characterizing central gland lesions. Combined diffusion-weighted (DW) imaging and dynamic contrast-enhanced MRI for distinguish malignant from benign prostate lesions can be used. The merged images, of DW and MRI with dynamic contrast enhancement, can visualise areas with low signal intensity and fast wash-out effect - characteristic of carcinomas.Lymphadenopathy can be seen best on postcontrast, fat-suppressed T1WI. Other regions can be described on MRI. The anterior fibromuscular stroma and the prostate capsule along the posterior and lateral prostate have a low T2WI signal, in contrast with the bright signal of the peripheral zone. Extraprostatic extension can be seen with disruption of capsule integrity.
MRI for the detection of prostate cancer
As of 2011, MRI was used to identify targets for prostate biopsy using fusion MRI with ultrasound (US) or MRI-guidance alone. One study reported that given a clinical suspicion, MRI-guided fusion biopsy detected clinically significant cancer in 38% compared to 26% in the standard biopsy group. In candidates for active surveillance, fusion MR/US-guided prostate biopsy detected 33% of cancers compared to 7% with standard ultrasound-guided biopsy.
Following an MRI, regions of interest within the scan which may be cancer are often graded on a likelihood scale between 1 and 5. One such scale is the prostate imaging-reporting and data system (PI-RADS) scale which defines standards of clinical service for multiparametric MRI (mpMRI), including image creation and reporting. PI-RADS version 2 scoring has shown a specificity and sensitivity of 73% and 95%, respectively, for detection of prostate cancer.
Other uses for MRI
Prostate MRI is also used for surgical planning for robotic prostatectomy. It helps surgeons decide whether to resect or spare the neurovascular bundle, determine return to urinary continence, and help assess surgical difficulty. MRI is used in other types of treatment planning, for both focal therapy and radiotherapy. MRI can also be used to target areas for research sampling in biobanking.
Biological basis for prostate cancer visibility on MRI
The biological properties which determine whether or not a tumour is visible on MRI is poorly understood. One theory is that tumour cells undergo several genetic changes during transformation which alter the cellular rate of growth and formation of new blood vessels, leading to tumours with more aggressive histological patterns, hypoxic regions and increased cell density among other features. Having larger, more dense tumours with changes in blood vessel distributions may feasibly alter signal on MRI through restriction of water and/or fluid movement.
Some studies have linked the presence of rare histological patterns within the tumour such as cribriform pattern. Although recent research suggests there is a number of histopathological features which may influence tumour detection by MRI. At a genetic level, prostate cancer visibility on MRI seems to be linked with genetic features of aggressive disease including processes such as cell proliferation, tumour hypoxia and DNA damage. The gene changes consistently observed in MRI-visible tumours include loss of tumour suppressor PTEN, increased expression of proliferation associated genes CENPF, AGR2 and growth factor GDF15 as well as a number of other genes. Changes in these pathways and genes may facilitate increased tumour growth, changes in vasculature and density which ultimately change the signal on MRI.
Ultrasound imaging can be obtained transrectally and is used during prostate biopsies. 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.
Prostate needle biopsy
If cancer is suspected, a biopsy is offered expediently. During a biopsy, a urologist or radiologist obtains tissue samples from the prostate via the rectum. 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. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization.
A histopathologic diagnosis mainly includes assessment of whether a cancer exists, as well as any subdiagnosis, if possible. Histopathologic subdiagnosis has implications for the possibility and methodology of Gleason scoring. The most common histopathological subdiagnosis is acinar adenocarcinoma, constituting 93% of diagnoses. The most common form of acinar adenocarcinoma, in turn, is "adenocarcinoma, not otherwise specified", also termed conventional, or usual acinar adenocarcinoma.
The Gleason grading system is used to help evaluate the prognosis and helps guide therapy. A Gleason score is based upon the tumor's appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 through 10, with a higher number indicating greater risks and higher mortality.
Tissue samples can be stained for the presence of PSA and other tumor markers to determine the origin of malignant cells that have metastasized.
The oncoproteinBCL-2 is associated with the development of androgen-independent prostate cancer, due to its high levels of expression in androgen-independent tumours in advanced stages. The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further established a connection between BCL-2 expression and prostate cancer progression.
Diagram showing T1-3 stages of prostate cancer.
An important part of evaluating prostate cancer is determining the stage, or degree of spread. Knowing the stage helps define prognosis and is useful when selecting therapies. The most common system is the four-stage TNM system (abbreviated from tumor/nodes/metastases). Its components include the size of the tumor, the number of involved lymph nodes, and the presence of any other metastases.
The most important distinction made by any staging system is whether the cancer is confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have metastasized. Several tests can be used to look for evidence of spread. Medical specialtyprofessional organizations recommend against the use of PET scans, CT scans, or bone scans when a physician stages early prostate cancer with low risk for metastasis. 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.
After a biopsy, a pathologist examines the samples under a microscope. If cancer is present, the pathologist reports the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The pathologist assigns a Gleason number from 1 to 5 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. The Whitmore-Jewett stage is another method.
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.
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
Diet and lifestyle
The data on the relationship between diet and prostate cancer are poor. However, the rate of prostate cancer is linked to the consumption of the Western diet. Little if any evidence associates trans fat, saturated fat, and carbohydrate intake and prostate cancer. Evidence does not offer a role for omega-3 fatty acids in preventing prostate cancer. Vitamin supplements appear to have no effect and some may increase the risk. High supplemental calcium intake has been linked to advanced prostate cancer.
Prostate cancer screening searches for cancers in those without symptoms. Options include the digital rectal exam and the PSA blood test. Such screening is controversial, and for many, may lead to unnecessary disruption and possibly harmful consequences. 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. Others recommend shared decision-making, an approach where screening may occur after a physician consultation.
American Urological Association (AUA 2013) guidelines call for weighing the uncertain benefits of screening against the known harms associated with diagnostic tests and treatment. 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. In the United Kingdom as of 2015, no program existed to screen for prostate cancer.
The first decision is whether treatment is needed. Low-grade forms found in elderly men often grows so slowly that treatment is not required. Treatment may also 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". 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).
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. A combination of treatment options is often recommended.
Although the widespread use of PSA screening in the US has resulted in diagnosis at earlier age and cancer stage, almost all cases are still diagnosed after age 65, while about 25% are diagnosed after age 75. 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.
Guidelines for specific clinical situations require estimation of life expectancy. 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. Therefore, interest grew in aggressive treatment modalities such as surgery or radiation even for localized disease.
Alternatively, 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.
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. 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.
Active surveillance involves monitoring the tumor for growth or symptoms, which trigger treatment. The monitoring process may involve PSA tests, digital rectal examination, and/or repeated biopsies every few months. 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. 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. 50 to 75% of patients die from other causes without experiencing prostate symptoms. In localized disease, neither radical prostatectomy nor watchful waiting has shown clearly superior results.
Both surgical and nonsurgical treatments are available, but treatment can be difficult, and combinations can be used. 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. 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. 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. Sipuleucel-T, a cancer vaccine, was reported to offer a four-month increase in survival in metastatic prostate cancer., but the marketing authorisation for it was withdrawn on 19 May 2015.
If radiation therapy fails, radical prostatectomy may be an option, though it is a technically challenging surgery. However, radiation therapy after surgical failure may have many complications. It is associated with a small increase in bladder and colon cancer. Radiotherapy and surgery appear to result in similar outcomes with respect to bowel, erectile and urinary function after five years.
Non-surgical treatment may involve radiation therapy, chemotherapy, hormonal therapy, external beam radiation therapy, and particle therapy, high-intensity focused ultrasound, or some combination.
Prostate cancer that persists when testosterone levels are lowered by hormonal therapy is called castrate-resistant prostate cancer (CRPC). 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.
Immunotherapy treatment with sipuleucel-T in CRPC appeared to increase survival by four months.. However, marketing authorisation for sipuleucel-T was withdrawn on 19 May 2015.The second line hormonal therapy abiraterone increases survival by 4.6 months.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.
Not all patients respond to androgen signaling-blocking drugs. Certain cells with characteristics resembling stem cells remain unaffected. Therefore, the desire to improve CRPC outcomes resulted in increasing doses or combination therapy with synergistic androgen-signaling blocking agents. But even these combination will not affect stem-like cells that do not exhibit androgen signaling.
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.
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. The prostate surrounds the urethra, a muscular tube that closes the urinary bladder. Any of the mentioned reasons can lead to incompetent closure of the urethra and hence incontinence. 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. The latter is considered the gold standard in patients with moderate or severe stress urinary incontinence.
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.
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). In Japan, the fatality rate rose to 8.6/100,000 in 2000. In India in the 1990s, half of those diagnosed with local cancer died within 19 years. One study reported that African-Americans have 50-60 times more deaths than found in Shanghai, China. In Nigeria, 2% of men develop prostate cancer, and 64% of them are dead after 2 years. Most Nigerian men present with metastatic disease with a typical survival of 40 months.
In patients who undergo treatment, the most important clinical prognostic indicators of disease outcome are the stage, pretherapy PSA level, and Gleason score. 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. 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. Because of this extensive inter-focal heterogeneity, it is a risk that the prognostication is set based on the wrong tumor focus.
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. How androgen-independence is established and how it re-establishes progression is unclear.
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. 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 table] 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. 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. It has been validated among over 10,000 prostatectomy patients, including patients from CaPSURE; the SEARCH registry, representing data from several Veterans Health Administration and military medical centers; a multi-institutional cohort in Germany; and the prostatectomy cohort at Johns Hopkins University. More recently, it has been shown to predict metastasis and mortality following prostatectomy, radiation therapy, watchful waiting, or androgen deprivation therapy.
Life expectancy projections are averages for an entire male population, and many medical and lifestyle factors modify these numbers. 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.
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.
Men with low-grade disease (Gleason 2-4) were unlikely to die of prostate cancer within 15 years of diagnosis. 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.
As of 2012, prostate cancer is the second-most frequently diagnosed cancer (at 15% of all male cancers) and the sixth leading cause of cancer death in males worldwide. In 2010, prostate cancer resulted in 256,000 deaths, up from 156,000 deaths in 1990. 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. Prostate cancer is least common among Asian men and most common among black men, with white men in between.
The average annual incidence rate of prostate cancer between 1988 and 1992 among Chinese men in the United States was 15 times higher than that of their counterparts living in Shanghai and Tianjin, but these high rates may be affected by higher rates of detection. Many suggest that prostate cancer may be under-reported, yet BPH incidence in China and Japan is similar to rates in Western countries.
More than 80% of men develop prostate cancer by age 80.
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.
Cases ranged from an estimated 230,000 in 2005 to an estimated 164,690 In 2018.
Deaths held steady around 30,000 in 2005 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. The estimated lifetime risk is about 14.0%, and the lifetime mortality risk is 2.6%.
Between 2005 and 2011, the proportion of disease diagnosed at a locoregional stage was 93% for whites and 92% for African Americans; the proportion of disease diagnosed at a late stage was 4% for whites and 5% for African Americans.
Prostate cancer is more common in the African American population than the White American population. An autopsy study of White and Asian men also found an increase in occult prostate cancer with age, 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, suggesting that Gleason score may be an imprecise indicator of clinically insignificant cases.
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.
In Europe in 2012, it was the third-most diagnosed cancer after breast and colorectal cancers at 417,000 cases.
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.
The prostate was first described by Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538. Prostate cancer was identified in 1853. 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.
Surgical removal of the testes (orchiectomy) to treat prostate cancer was first performed in the 1890s, with limited success. 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. This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function.
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.
People 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. In 2001, The Guardian noted that Britain had 3,000 nurses specializing in breast cancer, compared to a single nurse for prostate cancer. Waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer.
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. 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. Critics cite such figures when claiming that women's health is favored over men's health.
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.
Prostate cancer experiences significantly less media coverage than other, equally prevalent cancers, outcovered 2.6:1 by breast cancer.
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. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important for disease progression. Molecules that could successfully target alternative domains have emerged. Such therapies could provide an advantage; particularly in treating prostate cancers that are resistant to current therapies.
Galectin-3 is another potential target. Aberrant glycan profiles have been described in prostate cancer, and studies have found specific links between the galectin signature and prostate cancer.
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.
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. 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.
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. 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.
One active research area and non-clinically applied investigations involves non-invasive methods of tumor detection. 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.
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. The CDC's Evaluation of Genomic Applications in Practice and Prevention Working Group discourages clinical use.
^ abCaini 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): 329-38. doi:10.1016/j.canep.2014.06.002. PMID24986642.
^"Prostate Cancer Treatment". National Cancer Institute. 6 February 2018. Retrieved 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
^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): 121-5. doi:10.1097/01.ju.0000162061.40533.0f. PMID15947595.
^Breslow N, Chan CW, Dhom G, Drury RA, Franks LM, Gellei B, et al. (November 1977). "Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France". International Journal of Cancer. 20 (5): 680-8. doi:10.1002/ijc.2910200506. PMID924691. S2CID42501757.
^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): 2593-604. doi:10.1016/j.ejca.2010.07.028. PMID20843488.
^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. PMID10891514.
^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): 1401-8. doi:10.1056/NEJM199705153362001. PMID9145676.
^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): 819-24. doi:10.1016/j.purol.2009.06.002. PMID19945666.
^Qin X, Cui Y, Shen L, Sun N, Zhang Y, Li J, et al. (September 2013). "Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials". International Journal of Cancer. 133 (5): 1033-41. doi:10.1002/ijc.28038. PMID23338728. S2CID19830376.
^Heidegger I, Borena W, Pichler R (May 2015). "The role of human papilloma virus in urological malignancies". Anticancer Research. 35 (5): 2513-9. PMID25964524.
^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. PMID30160386.
^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. PMID27871956.
^"Male Genitals - Prostate Neoplasms". Pathology study images. University of Virginia School of Medicine. Archived from the original on 2011-07-20. Retrieved . 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.
^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): 840-3. PMID19947572.
^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): 787-93. doi:10.1007/s00432-009-0718-x. PMID19946707. S2CID34855148.
^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): 305-16. doi:10.1002/pros.21065. PMID19830782. S2CID21518526.
^Truong, Matthew; Hollenberg, Gary; Weinberg, Eric; Messing, Edward M.; Miyamoto, Hiroshi; Frye, Thomas P. (August 2017). "Impact of Gleason Subtype on Prostate Cancer Detection Using Multiparametric Magnetic Resonance Imaging: Correlation with Final Histopathology". The Journal of Urology. 198 (2): 316-321. doi:10.1016/j.juro.2017.01.077. ISSN1527-3792. PMID28163032. S2CID45430609.
^ abWei ZF, Xu H, Wang H, Wei W, Cheng W, Zhou WQ, et al. (September 2009). "[Clinicopathological characterization of prostatic small cell carcinoma: a case report and review of the literature]". Zhonghua Nan Ke Xue (in Chinese). 15 (9): 829-32. PMID19947569.
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. PMID22088337.
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): 2106-31. doi:10.1016/j.juro.2007.03.003. PMID17509297.
^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. PMID29317772. S2CID3306182.
^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): 810-7. doi:10.1016/j.purol.2009.02.008. PMID19945664.
^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. PMID19945310.
^Dhondt B, De Bleser E, Claeys T, Buelens S, Lumen N, Vandesompele J, et al. (December 2018). "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. PMID30578441. S2CID58594673.
^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]". Progrès en Urologie (in French). 19 (11): 803-9. doi:10.1016/j.purol.2009.04.010. PMID19945663.
^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): 1147-54. doi:10.1016/S0140-6736(10)61389-X. PMID20888992. S2CID4791847.
^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): 207-12. PMID15714967.
^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. PMID1259345.
^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. PMID17868719.
^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. PMID18372031.
^Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW (July 2003). "Soy and isoflavone consumption in relation to prostate cancer risk in China". Cancer Epidemiology, Biomarkers & Prevention. 12 (7): 665-8. PMID12869409.
^Potosky AL, Miller BA, Albertsen PC, Kramer BS (February 1995). "The role of increasing detection in the rising incidence of prostate cancer". JAMA. 273 (7): 548-52. doi:10.1001/jama.273.7.548. PMID7530782.
^Hanno P.M., Malcowicz S.B., Wein A.J., "Clinical Manual of Urology" McGraw Hill 2001
^Homma Y, Kawabe K, Tsukamoto T, Yamanaka H, Okada K, Okajima E, et al. (January 1997). "Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score". International Journal of Urology. 4 (1): 40-6. doi:10.1111/j.1442-2042.1997.tb00138.x. PMID9179665. S2CID19636484.
^Ghabili, Kamyar; Tosoian, Jeffrey J.; Schaeffer, Edward M.; Pavlovich, Christian P.; Golzari, Samad E.J.; Khajir, Ghazal; Andreas, Darian; Benzon, Benjamin; Vuica-Ross, Milena; Ross, Ashley E. (November 2016). "The History of Prostate Cancer From Antiquity: Review of Paleopathological Studies". Urology. 97: 8-12. doi:10.1016/j.urology.2016.08.032. PMID27591810.
^Adams J (1853). "The case of scirrhous of the prostate gland with corresponding affliction of the lymphatic glands in the lumbar region and in the pelvis". Lancet. 1 (1547): 393-94. doi:10.1016/S0140-6736(02)68759-8.
^Scott WW, Johnson DE, Schmidt JE, Gibbons RP, Prout GR, Joiner JR, et al. (December 1975). "Chemotherapy of advanced prostatic carcinoma with cyclophosphamide or 5-fluorouracil: results of first national randomized study". The Journal of Urology. 114 (6): 909-11. doi:10.1016/S0022-5347(17)67172-6. PMID1104900.
^ abcGreene ER, Huang S, Serhan CN, Panigrahy D (November 2011). "Regulation of inflammation in cancer by eicosanoids". Prostaglandins & Other Lipid Mediators. 96 (1-4): 27-36. doi:10.1016/j.prostaglandins.2011.08.004. PMC4051344. PMID21864702. The 5-lipoxygenase (5-LOX) pathway is implicated in the development and progression of human cancers. 5-LOX, whose crystal structure was recently identified (118), is a key enzyme in metabolizing arachidonic acid to leukotrienes. 5-LOX can be induced by proinflammatory stimuli and is expressed in epithelial cancers including lung, prostate, breast, and colon (113). Hence, 5-LOX inhibitors have been targeted for their chemopreventive effects. Inhibition of 5-LOX activity is shown to block prostate cancer cell proliferation as well as carcinogen-induced lung tumorigenesis (119, 120). ... Both 5-HETE and 12-HETE are also products of lipoxygenase and are involved in tumor progression (12). Exogenous 5-HETE can stimulate the proliferation of prostate cancer cells and act as a survival factor (137, 138). These results require relatively high concentrations (at a concentration of 10 ?M). Blocking the formation of 5-HETE, by inhibiting 5-lipoxygenase, results in massive apoptosis of human prostate cancer cells (139).
^ abcBishayee K, Khuda-Bukhsh AR (September 2013). "5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy". Acta Biochimica et Biophysica Sinica. 45 (9): 709-19. doi:10.1093/abbs/gmt064. PMID23752617. Recent studies demonstrated the involvement of growth factors, such as epidermal growth factor (EGF) and neurotensin in the 5-LOX-mediated tumor progression in prostate cancer [22,23]. Recent studies with 5-LOX siRNA  and specific blocker of 5-LOX  revealed the relation of this gene with the tumor cell proliferation. ... Meclofenamate sodium (MS) is known for its anti-inflammatory activity, and apart from this, Boctor et al.  reported that it caused reduction in the formation of 5-HETE in human leucocytes when used. MS can thus be considered a dual inhibitor of 5-LOX and COX pathways of arachidonic acid cascade. Further investigation with this substance revealed that it could interfere with the LT receptors in the lung carcinoma . In a recent study, a group of scientists have shown the effect of MS on prostate cancer cells both in vitro and in vivo , and their result suggests a profound reduction in the tumor growth and cancer metastasis. ... While the commonly used inhibitors produced strong cytotoxicity, notably, zileuton, the only commercialized 5-LOX inhibitor, failed to induce an anti-proliferative or cytotoxic response in all other types of tumor cells where 5-LOX was in inactive state (e.g. HeLa cells). But where 5-LOX was in active state, zileuton could effectively inhibit progression, as in case of prostate cancer.
^Kokontis JM, Hsu S, Chuu CP, Dang M, Fukuchi J, Hiipakka RA, Liao S (December 2005). "Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity". The Prostate. 65 (4): 287-98. doi:10.1002/pros.20285. PMID16015608. S2CID22349673.