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March 26, 2016
Table of Contents

1 Introduction
prostate cancer

Wikipedia

 

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize (spread) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating , problems during sexual intercourse, or erectile dysfunction. Other symptoms can potentially develop during later stages of the disease.

Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States. Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men, many never have symptoms, undergo no therapy, and eventually die of other causes. This is because cancer of the prostate is, in most cases, slow-growing, symptom-free, and since men with the condition are older they often die of causes unrelated to the prostate cancer, such as heart/circulatory disease, pneumonia, other unconnected cancers, or old age. About 2/3 of cases are slow growing, the other third more aggressive and fast developing.

Many factors, including genetics and diet , have been implicated in the development of prostate cancer. The presence of prostate cancer may be indicated by symptoms, physical examination, prostate specific antigen (PSA), or biopsy. The PSA test increases cancer detection but does not decrease mortality. Suspected prostate cancer is typically confirmed by taking a biopsy of the prostate and examining it under a microscope. Further tests, such as CT scans and bone scans, may be performed to determine whether prostate cancer has spread.

Treatment options for prostate cancer with intent to cure are primarily surgery, radiation therapy, and proton therapy. Other treatments, such as hormonal therapy , chemotherapy, cryosurgery, and high intensity focused ultrasound (HIFU) also exist, depending on the clinical scenario and desired outcome.

The age and underlying health of the man, the extent of metastasis, appearance under the microscope, and response of the cancer to initial treatment are important in determining the outcome of the disease. The decision whether or not to treat localized prostate cancer (a tumor that is contained within the prostate) with curative intent is a patient trade-off between the expected beneficial and harmful effects in terms of patient survival and quality of life.




The prostate is a part of the male reproductive organ that helps make and store seminal fluid. In adult men, a typical prostate is about three centimeters long and weighs about twenty grams. 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. Because of its location, prostate diseases often affect urination, ejaculation, and rarely defecation. The prostate contains many small glands which make about twenty percent of the fluid constituting semen. In prostate cancer, the cells of these prostate glands mutate into cancer cells. The prostate glands require male hormones, known as androgens, to work properly. Androgens include testosterone, which is made in the testes; 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.




An important part of evaluating prostate cancer is determining the stage , or how far the cancer has 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 or not the cancer is still 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 spread elsewhere. Several tests can be used to look for evidence of spread. These include computed tomography to evaluate spread within the pelvis, bone scans to look for spread to the bones, and endorectal coil magnetic resonance imaging to closely evaluate the prostatic capsule and the seminal vesicles. Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis???opposite to what is found in many other cancers that metastasize.

Computed tomography (CT) and magnetic resonance imaging (MRI) currently do not add any significant information in the assessment of possible lymph node metastases in patients with prostate cancer according to a meta-analysis. The sensitivity of CT was 42% and specificity of CT was 82%. The sensitivity of MRI was 39% and the specificity of MRI was 82%. For patients at similar risk to those in this study (17% had positive pelvic lymph nodes in the CT studies and 30% had positive pelvic lymph nodes in the MRI studies), this leads to a positive predictive value (PPV) of 32.3% with CT, 48.1% with MRI, and negative predictive value (NPV) of 87.3% with CT, 75.8% with MRI.

After a prostate biopsy, a pathologist looks at 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 Gleason system is used to grade prostate tumors from 2 to 10, where a Gleason score of 10 indicates the most abnormalities. The pathologist assigns a 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 sometimes used.




Early prostate cancer usually causes no symptoms. Often it is diagnosed during the workup for an elevated PSA noticed during a routine checkup.

Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hyperplasia. These include frequent urination , increased urination at night , difficulty starting and maintaining a steady stream of urine, blood in the urine , and painful urination . Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland, therefore, directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate gland itself are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.

Advanced prostate cancer can spread to other parts of the body, possibly causing additional symptoms. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the proximal part of the bone. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.




The specific causes of prostate cancer remain unknown. The primary risk factors are age and family history. Prostate cancer is very uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. However, many men never know they have prostate cancer. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes have found prostate cancer in thirty percent of men in their 50s, and in eighty percent of men in their 70s. Men who have first-degree family members with prostate cancer appear to have double the risk of getting the disease compared to men without prostate cancer in the family. This risk appears to be greater for men with an affected brother than for men with an affected father. In the United States in 2005, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer. Men with high blood pressure are more likely to develop prostate cancer. A 2010 study found that prostate basal cells were the most common site of origin for prostate cancers.

Genetic

Genetic background may contribute to prostate cancer risk, as suggested by associations with race, family, and specific gene variants. Men with one first-degree relative with prostate cancer have a twofold higher risk, and those with two first-degree relatives have a fivefold greater risk of developing prostate cancer compared with men with no family history. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men.

No single gene is responsible for prostate cancer; many different genes have been implicated. Mutations in BRCA1 and BRCA2, important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer.

Loss of cancer suppressor genes,early in the 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 late event in pathology of prostate cancer. Other tumor suppressor genes that are thought to play a role in prostate cancer include PTEN (gene) 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.

Diet

Evidence from epidemiological studies supports a possible protective role in reducing prostate cancer for dietary Vitamin B6, selenium, vitamin E, lycopene, and soy foods. A study in 2007 cast doubt on the effectiveness of lycopene (found in tomatoes) in reducing the risk of prostate cancer. Lower blood levels of vitamin D may increase the risk of developing prostate cancer. This may be linked to lower exposure to ultraviolet (UV) light , since UV light exposure can increase vitamin D in the body.

Studies comparing men who live in areas of the country with high levels of selenium to men in areas with low levels suggest that this mineral protects against prostate cancer. Selenium is believed to reduce the risk of developing prostate cancer because it keeps cells from proliferating or dying off in a rapid or unusual way. An analysis in 2002 of the Nutritional Prevention of Cancer Trial revealed that the men who took selenium supplements daily were half as likely to be diagnosed with prostate cancer. These findings have been confirmed in most observational studies. However, in 2008, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicated that neither selenium nor vitamin E, alone or in combination, was effective for the primary prevention of prostate cancer.

Green tea may be protective (due to its polyphenol content),

Research published in the Journal of the National Cancer Institute suggests that taking multivitamins more than seven times a week can increase the risks of contracting the disease. This research was unable to highlight the exact vitamins responsible for this increase (almost double), although they suggest that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised that those taking multivitamins never exceed the stated daily dose on the label.

A 2007 study published in the Journal of the National Cancer Institute found that men eating cauliflower, broccoli, or one of the other cruciferous vegetables, more than once a week were 40% less likely to develop prostate cancer than men who rarely ate those vegetables.

Many doctors prescribe supplements to prostate cancer patients but currently the efficacy of nutrient supplements is still unknown. Supplements may not be as beneficial to prostate health as micronutrients obatined naturally from the diet.

Folic acid supplements have recently been linked to an increase in risk of developing prostate cancer. A ten-year research study led by University of Southern California researchers showed that men who took daily folic acid supplements of 1 mg were three times more likely to be diagnosed with prostate cancer than men who took a placebo. Folate hydrolase activity is associated with prostate-specific antigen.

A small Swedish study of 254 subjects, with a median age of 64, and a follow up of 5 years suggested that folate status is not protective against prostate cancer, however, and like folic acid may even result in a 3 fold increase in early prostate cancer development and risk. Supplements and multivitamins, alcohol and drug consumption, GI disorders, and folate bioavailability were not analyzed in this study.

High alcohol intake may increase the risk of prostate cancer and interfere with folate metabolism. Low folate intake and high alcohol intake may increase the risk of prostate cancer to a greater extent than the sole effect of either one by itself.

The prostate gland has a high concentration of zinc so zinc may play a role in prostate cancer. Researchers studied the relationship between zinc supplement intake of 100 mg/day and the risk of prostate cancer in 46 974 US men over a 14 year period and reported in 2003 that long term zinc supplement of over 100 mg/day intake seemed to be associated with approximately double the risk of developing prostate cancer.

Medication exposure

There are also some links between prostate cancer and medications, medical procedures, and medical conditions..

Infection or inflammation of the prostate ( prostatitis) may increase the chance for prostate cancer while another study shows infection may help prevent prostate cancer by increasing blood to the area. In particular, infection with the sexually transmitted infections chlamydia , gonorrhea, or syphilis seems to increase risk.

Research released in May 2007, found that US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.

Viral

In 2006, researchers associated a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, with human prostate tumors.




Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that begins when normal semen-secreting prostate gland cells mutate into cancer cells. The region of prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN). Although there is no proof that PIN is a cancer precursor, it is closely associated with cancer. Over time, these cancer cells begin to 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 the tumor cells may develop the ability to travel in the bloodstream and lymphatic system. Prostate cancer is considered a malignant tumor because it is a mass of cells that can invade other parts of the body. This invasion of other organs is called metastasis. Prostate cancer most commonly metastasizes to the bones, lymph nodes, rectum, and bladder.

The prostate is a zinc accumulating, citrate producing organ. The protein ZIP1 is responsible for the active transport of zinc into prostate cells. One of zinc's important roles is to change the metabolism of the cell in order to produce citrate, an important component of semen. The process of zinc accumulation, alteration of metabolism, and citrate production is energy inefficient, and prostate cells sacrifice enormous amounts of energy (ATP) in order to accomplish this task. Prostate cancer cells are generally devoid of zinc. This allows prostate cancer cells to save energy not making citrate, and utilize the new abundance of energy to grow and spread. The absence of zinc is thought to occur via a silencing of the gene that produces the transporter protein ZIP1. ZIP1 is now called a tumor suppressor gene product for the gene SLC39A1. The cause of the epigenetic silencing is unknown. Strategies which transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits NF-??B pathways, is anti-proliferative, 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 the active transporter, ZIP1.

RUNX2 is a transcription factor that prevents cancer cells from undergoing apoptosis thereby contributing to the development of prostate cancer.

The PI3k/Akt signaling cascade works with the transforming growth factor beta/SMAD signaling cascade to ensure prostate cancer cell survival and protection against apoptosis.

The androgen receptor helps prostate cancer cells to survive and is a target for many anti cancer research studies; so far, inhibiting the androgen receptor has only proven to be effective in mouse studies.

Prostate specific membrane antigen (PSMA) stimulates the development of prostate cancer by increasing folate levels for the cancer cells to use to survive and grow; PSMA increases available folates for use by hydrolyzing glutamated folates.




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. However, prior to a biopsy, several other tools may be used to gather more 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 down the urethra. Transrectal ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum.

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. Fifty-five percent of men report discomfort during prostate biopsy.

Gleason score

The tissue samples are then examined under a microscope to determine whether cancer cells are present, and to evaluate the microscopic features (or Gleason score) of any cancer found. Prostate specific membrane antigen is a transmembrane carboxypeptidase and exhibits folate hydrolase activity. This protein is overexpressed in prostate cancer tissues and is associated with a higher Gleason score.

Tumor markers

Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of malignant cells that have metastasized.

Small cell carcinoma is a very rare (1% researchers are trying to determine the best way to screen for this type of prostate cancer because it is a relatively unknown and rare type of prostate cancer but very serious and quick to spread to other parts of the body.

Possible methods include chromatographic separation methods by mass spectrometry, or protein capturing by immunoassays or immunized antibodies. The test method will involve quantifying the amount of the biomarker PCI , with reference to the Gleason Score. Not only is this test quick, it is also sensitive. It can detect patients in the diagnostic grey zone, particularly those with a serum free to total Prostate Specific Antigen ratio of 10-20%.

The oncoprotein BCL-2, has been associated with the development of androgen-independent prostate cancer due to its high levels of expression in androgen-independent tumours in advanced stages of the pathology. 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.

The expression of Ki-67 by immunohistochemistry may be a significant predictor of patient outcome for men with prostate cancer.

Under investigation

At present, an active area of research involves non-invasive methods of prostate tumor detection. Adenoviruses modified to transfect tumor cells with harmless yet distinct genes (such as luciferase) have proven capable of early detection. So far, however, this area of research has been tested only in animal and LNCaP cell models.

PCA3

Another potential non-invasive method of early prostate tumor detection is through a molecular test that detects the presence of cell-associated PCA3 mRNA in urine. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. PCA3 is not a replacement for PSA but an additional tool to help decide whether, in men suspected of having prostate cancer, a biopsy is really needed. The higher the expression of PCA3 in urine, the greater the likelihood of a positive biopsy, i.e., the presence of cancer cells in the prostate.

Early prostate cancer antigen-2

It was reported in April 2007 that a new blood test for early prostate cancer antigen-2 (EPCA-2) that may alert men if they have prostate cancer and how aggressive it will be is being researched.

Thrombophlebitis is associated with an increased risk of prostate cancer and may be a good way for physicians to remind themselves to screen patients with thrombophlebitis for prostate cancer as well since these two are closely linked.

Prostate mapping

Prostate mapping is a method of diagnosis that may be accurate in determining the precise location and aggressiveness of a tumor. It uses a combination of multi-sequence MRI imaging techniques and a template-guided biopsy system, and involves taking multiple biopsies through the skin that lies in front of the rectum rather than through the rectum itself. The procedure is carried out under general anesthetic.

Prostasomes

Epithelial cells of the prostate secrete prostasomes as well as PSA . Prostasomes are membrane???surrounded, prostate-derived organelles that appear extracellularly, and one of their physiological functions is to protect the sperm from attacks by the female immune system. Cancerous prostate cells continue to synthesize and secrete prostasomes, and may be shielded against immunological attacks by these prostasomes. Research of several aspects of prostasomal involvement in prostate cancer has been performed.




Prostate cancer screening is an attempt to find unsuspected cancers, and may lead to more specific follow-up tests such as a biopsy, with cell samples taken for closer study. Options include the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. A 2010 analysis concluded that routine screening with either a DRE or PSA is not supported by the evidence as there is no mortality benefit from screening.

Modern screening tests have found cancers that might never have developed into serious disease, and that "the slight reduction of risk by surgically removing the prostate or treating it with radiation may not outweigh the substantial side effects of these treatments," an opinion also shared by the CDC .




A comprehensive worldwide report compiled by the World Cancer Research Fund and the American Institute for Cancer Research reports a significant relation between lifestyle (including food consumption) and cancer prevention. Other research also supports this finding. The potential role of diet in preventing prostate cancer is discussed in greater detail in the diet section of this article.

Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride

and dutasteride, In the original study it turns out that the smaller prostate caused by finasteride means that a doctor is more likely to hit upon cancer nests and more likely to find aggressive-looking cells.

Ejaculation frequency

More frequent ejaculation also may decrease a man's risk of prostate cancer. One study showed that men who ejaculated five times a week in their 20s had a decreased rate of prostate cancer, though other studies have shown no benefit.

Diet

Oils and fatty acids

In experimental models using mice have been tested, dietary and serum omega-6 polyunsaturated fatty acids (PUFAs) increased prostate tumor growth,and has sped up histopathological progression, and decreased survival, while the omega-3 fatty acids, in the same situation, had the opposite, beneficial effect.

Men with high serum linoleic acid, but not palmitic, can reduce the risk of prostate cancer by taking tocopherol supplementation.

Men with elevated levels of long-chain omega-3 fatty acids ( EPA and DHA ) had lowered incidence.

A long-term study reports that "blood levels of trans fatty acids, in particular trans fats resulting from the hydrogenation of vegetable oils, are associated with an increased prostate cancer risk."

Some researchers have indicated that serum myristic acid saturated fatty acids and serum palmitic combined with alpha-tocopherol supplementation are associated with increased risk of prostate cancer in a dose-dependent manner. These associations may, however, reflect differences in intake or metabolism of these fatty acids between the precancer cases and controls, rather than being an actual cause.

Other

Vegetarian: The American Dietetic Association and Dieticians of Canada report a decreased incidence of prostate cancer for those following a vegetarian diet.

Low-carb : In lab tests on mice, prostate tumors grow slower with a no-carbohydrate diet.

Coffee: A preliminary study found a correlation between coffee consumption and a lower risk of aggressive prostate cancer.




Treatment for prostate cancer may involve active surveillance (monitoring for tumor progress or symptoms), surgery (i.e. radical prostatectomy), radiation therapy including brachytherapy ( prostate brachytherapy) and external beam radiation therapy, High-intensity focused ultrasound (HIFU), chemotherapy, oral chemotherapeutic drugs (Temozolomide/TMZ), cryosurgery, hormonal therapy , or some combination.

Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effect s, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. Prostate cancer patients are strongly recommended to work closely with their physicians and use a combination of the treatment options when managing their prostate cancer.

The selection of treatment options may be a complex decision involving many factors. For example, radical prostatectomy after primary radiation failure is a very technically challenging surgery and may not be an option, while salvage radiation therapy after surgical failure may have many complications. This may enter into the treatment decision.

If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors that treat prostate cancer use a variety of nomograms to predict the probability of spread. Treatment by watchful waiting/active surveillance, external beam radiation therapy, brachytherapy, cryosurgery, HIFU, and surgery are, in general, offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for disease that has spread beyond the prostate. However, there are exceptions: radiation therapy may be used for some advanced tumors, and hormonal therapy is used for some early stage tumors. Cryotherapy (the process of freezing the tumor), hormonal therapy , and chemotherapy may also be offered if initial treatment fails and the cancer progresses.

Hormone-refractory prostate cancer (HRPC)

Most hormone dependent cancers become refractory (independent) after one to three years and resume growth despite hormone therapy.

Docetaxel has been used for HRPC with a median survival benefit of 2 to 3 months.

A combination of bevacizumab(Avastin), taxotere, thalidomide and prednisone appears effective in the treatment of hormone-refractory prostate cancer.

Provenge is also effective (better than placebo) in the treatment of hormone-refractory prostate cancer, as is Cabazitaxel.

MDV3100 is in phase II/III trials currently.

Abiraterone showed good results in a phase 2 trial and is in two phase 3 clinical trials.




Prostate cancer rates are higher and prognosis poorer in developed countries than the rest of the world. Many of the risk factors for prostate cancer are more prevalent in the developed world, including longer life expectancy and diets high in red meat (People that consume larger amounts of meat and dairy also tend to consume fewer portions of fruits and vegetables. It is not currently clear whether both of these factors, or just one of them, contribute to the occurrence of prostate cancer.) Also, where there is more access to screening programs, there is a higher detection rate. Prostate cancer is the ninth-most-common cancer in the world, but is the number-one non-skin cancer in United States men. Prostate cancer affected eighteen percent of American men and caused death in three percent in 2005.

In patients that undergo treatment, the most important clinical prognostic indicators of disease outcome are stage, pre-therapy PSA level and Gleason score. In general, 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 suffering from cancers at various stages.

In 1941, Charles Huggins reported that androgen ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer. 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. The actual mechanism contributes to the progression of prostate cancer is not clear and may vary between individual patient. A few possible mechanisms have been proposed.

Classification systems

Many prostate cancers are not destined to be lethal, and most men will ultimately die from causes other than of the disease. Decisions about treatment type and timing may, therefore, be informed by an estimation of the risk that the tumor will ultimately recur after treatment and/or progress to metastases and mortality. 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 also add the number or percent 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 3-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 predict pathologic outcomes (margin status, extraprostatic extension, and seminal vesicle invasion) based on the same 3 variables, and are published as lookup tables.

  • The Kattan nomograms predict recurrence after surgery and/or radiation therapy, based on data available either at time of diagnosis or after surgery. The nomograms can be calculated using paper graphs, or using software available on a website or for handheld computers. 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 comparable accuracy as the Kattan preoperative nomogram, and can be calculated without paper tables or a calculator. Points are assigned based on PSA, Grade, stage, age, and percent of cores positive; the sum yields a 0???10 score, with every 2 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 Administration and active 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.




Rates of prostate cancer vary widely across the world. Although the rates vary widely between countries, it is least common in South and East Asia, more common in Europe, and most common in the United States. According to the American Cancer Society, prostate cancer is least common among Asian men and most common among black men, with figures for white men in between. However, these high rates may be affected by increasing rates of detection.

Prostate cancer develops primarily in men over fifty. It is the most common type of cancer in men in the United States, with 186,000 new cases in 2008 and 28,600 deaths. It is the second leading cause of cancer death in U.S. men after lung cancer. In the United Kingdom it is also the second most common cause of cancer death after lung cancer, where around 35,000 cases are diagnosed every year and of which around 10,000 die of it. Many factors, including genetics and diet , have been implicated in the development of prostate cancer. The Prostate Cancer Prevention Trial found that finasteride reduces the incidence of prostate cancer rate by 30%. There had been a controversy about this also increasing the risk of more aggressive cancers, but more recent research showed this may not be the case.




Although the prostate was first described by Venetian anatomist Niccol?? Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538, prostate cancer was not identified until 1853. Prostate cancer was initially considered a rare disease, probably because of shorter life expectancies and poorer detection methods in the 19th century. The first treatments of prostate cancer were surgeries to relieve urinary obstruction. Removal of the entire gland (radical perineal prostatectomy) was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital. Surgical removal of the testes ( orchiectomy) to treat prostate cancer was first performed in the 1890s, but 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.

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. The role of the hormone GnRH in reproduction was determined by Andrzej W. Schally and Roger Guillemin, who both won the 1977 Nobel Prize in Physiology or Medicine for this work.

Receptor agonists, such as leuprolide and goserelin, were subsequently developed and used to treat prostate cancer.

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

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

On 30 July 2010 Owen Witte M.D. et al. of UCLA published a series of studies in Science during which they had introduced viruses known to cause cancerous mutation in prostate cells: AKT, ERG, and AR into isolated samples of basal and luminal cells and grafted the treated tissue into mice. After 16 weeks, none of the luminal samples had undergone malignant mutation, while the basal samples had mutated into prostate-like tubules which had then developed malignancy and formed cancerous tumors, which appeared identical to human samples under magnification. This led to the conclusion that the prostate basal cell may be the most likely "site of origin" of prostate cancer.




Androgen at a concentration of 10-fold higher than the physiological concentration has also been shown to cause growth suppression and reversion of androgen-independent prostate cancer xenografts or androgen-independent prostate tumors derived in vivo model to an androgen-stimulated phenotype in athymic mice. These observation suggest the possibility to use androgen to treat the development of relapsed androgen-independent prostate tumors in patients.

Oral infusion of green tea polyphenols, a potential alternative therapy for prostate cancer by natural compounds, has been shown to inhibit the development, progression, and metastasis as well in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops prostate cancer.

The insulin-like growth factor signaling axis is thought to play a key role in the progression of prostate carcinoma. It consists of two ligands ( IGF-1 and IGF-2), two receptors (IGF-IR and IGF-IIR) and six related high-affinity IGF-binding proteins (IGFBP 1-6). Altered expression of IGF axis members has been implicated in the development of many different types of cancers, including prostate.

A genistein derivative KBU2046 is under investigation for prostate cancer.

The Color of Prostate Cancer Awareness is Light Blue.

Prostate cancer models

Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. 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 androgen receptor (AR); however, PC-3 and DU-145 cells express very little or no AR. AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important during the development of prostate cancer. 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. The paradox is that androgens inhibit the proliferation of these androgen-independent prostate cancer cells.





  • Prostate Cancer Clinical Trials Search and learn about clinical trials for prostate cancer

  • Prostate Cancer From Cancer Management: A Multidisciplinary Approach

  • Prostate Cancer & Endothelin : PMAP The Proteolysis Map-animation

  • Interactive Health Tutorials Medline Plus: What's Prostate Cancer Using animated graphics and you can also listen to the tutorial

  • Highlights of ASCO 2007 Prostate Symposium , Anna Ferrari. Overview for doctors of ongoing European and U.S. clinical studies of prostate cancer presented at the New York Cancer Consortium . Data on screening, and treatment of local, intermediate and advanced prostate cancer by surgery, radiation and hormones. Answering the question, "What do we tell our patients about treatment decisions?"

  • "Prostate Cancer Treatments"

  • Prostate Cancer Prevention - World Foundation of Urology



This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "prostate cancer".


Last Modified:   2010-11-25


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