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Prostate cancer
SpecialtyOncology, urology Edit this on Wikidata

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.[1] 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.[2] 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 two-thirds of cases are slow growing, the other third more aggressive and fast developing.[3]

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.[4] 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, stereotactic radiosurgery, and proton therapy. Other treatments, such as hormonal therapy, chemotherapy, cryosurgery, and high intensity focused ultrasound (HIFU) also exist, although not FDA approved, 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.

Overview

See also: Prostate

The prostate is a part of the male reproductive system that helps make and store seminal fluid. In adult men, a typical prostate is about three centimeters long and weighs about twenty grams.[5] 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.[6] 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.[7] 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.

Classification

Main article: Prostate cancer staging

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.[8]

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.

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.

Signs and symptoms

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, nocturia (increased urination at night), difficulty starting and maintaining a steady stream of urine, hematuria (blood in the urine), and dysuria (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.[9]

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.[10]

Causes

The specific causes of prostate cancer remain unknown.[11] 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.[12] 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.[13] 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.[14] 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.[15] Men with high blood pressure are more likely to develop prostate cancer.[16] A 2010 study found that prostate basal cells were the most common site of origin for prostate cancers.[17]

Genetic

Genetic background may contribute to prostate cancer 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 fivefold greater risk compared with men with no family history.[18] In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men.[19] [20] In contrast, the incidence and mortality rates for Hispanic men are one third lower than for non-Hispanic whites. Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained by inherited factors.[21]

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.[22] Other linked genes include the Hereditary Prostate cancer gene 1 (HPC1), the androgen receptor, and the vitamin D receptor.[19] TMPRSS2-ETS gene family fusion, specifically TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes cancer cell growth.[23]

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"[24] Relative frequency of loss of E-cadherin and CD44 has also been observed.

Dietary

While a number of dietary factors have been linked to prostate cancer the evidence is still tentative.[25] Evidence supports little role for dietary fruits and vegetables in prostate cancer occurrence.[26] Red meat and processed meat also appear to have little effect.[27] Lower blood levels of vitamin D may increase the risk of developing prostate cancer.[28] This may be linked to lower exposure to ultraviolet (UV) light, since UV light exposure can increase vitamin D in the body.[29]

Green tea may be protective (due to its catechins content),[30] although the most comprehensive clinical study indicates that it has no protective effect.[31] Other holistic methods are also studied.[32]

Taking multivitamins more than seven times a week may increase the risks of contracting the disease.[33][34] 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.

Folic acid supplements have recently been linked to an increase in risk of developing prostate cancer.[35] 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.[35]

High alcohol intake may increase the risk of prostate cancer and interfere with folate metabolism.[36] 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.[36] A case control study consisting of 137 veterans addressed this hypothesis and the results were that high folate intake was related to a 79% lower risk of developing prostate cancer and there was no association between alcohol consumption by itself and prostate cancer risk.[36] Folate's effect however was only significant when coupled with low alcohol intake.[36] There is a significant decrease in risk of prostate cancer with increasing dietary folate intake but this association only remains in individuals with low levels of alcohol consumption.[36] There was no association found in this study between folic acid supplements and risk of prostate cancer.[36]

Medication exposure

There are also some links between prostate cancer and medications, medical procedures, and medical conditions.[37] Use of the cholesterol-lowering drugs known as the statins may also decrease prostate cancer risk.[38]

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.[39] Finally, obesity[40] and elevated blood levels of testosterone[41] may increase the risk for prostate cancer. There is an association between vasectomy and prostate cancer however more research is needed to determine if this is a causative relationship.[42]

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.[43]

Viral

In 2006, researchers associated a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, with human prostate tumors.[44] Subsequent reports on the virus have been contradictory. A group of US researchers found XMRV protein expression in human prostate tumors,[45] while German scientists failed to find XMRV-specific antibodies or XMRV-specific nucleic acid sequences in prostate cancer samples.[46]

Pathophysiology

File:Normal cancer cell division from NIH-2.svg
When normal cells are damaged beyond repair, they are eliminated by apoptosis. Cancer cells avoid apoptosis and continue to multiply in an unregulated manner.

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, and may invade 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.[47]

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-κB 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.[48]

RUNX2 is a transcription factor that prevents cancer cells from undergoing apoptosis thereby contributing to the development of prostate cancer.[49]

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.[50] X-linked inhibitor of apoptosis (XIAP) is hypothesized to promote prostate cancer cell survival and growth and is a target of research because if this inhibitor can be shut down then the apoptosis cascade can carry on its function in preventing cancer cell proliferation.[51] Macrophage inhibitory cytokine-1 (MIC-1) stimulates the focal adhesion kinase (FAK) signaling pathway which leads to prostate cancer cell growth and survival.[52]

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.[53] 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.[54]

Diagnosis

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 (DRE) 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

Main article: Prostate biopsy
Micrograph showing a prostate cancer (conventional adenocarcinoma) with perineural invasion. H&E stain.

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.[55]

Gleason score

Main article: 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.[35] This protein is overexpressed in prostate cancer tissues and is associated with a higher Gleason score.[35]

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.[56]

Small cell carcinoma is a very rare (1%[57]) type of prostate cancer that cannot be diagnosed using the PSA.[57][58] As of 2009 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.[58] 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%.[59]

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.[60]

The expression of Ki-67 by immunohistochemistry may be a significant predictor of patient outcome for men with prostate cancer.[61]

ERK5 is a protein that may be used as a marker. ERK5 is present in abnormally high levels of prostate cancer, including invasive cancer which has spread to other parts of the body. It is also present in relapsed cancer following previous hormone therapy. Research shows that reducing the amount of ERK5 found in cancerous cells reduces their invasiveness. [62]

Screening

Main article: Prostate cancer screening

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.[4]

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.[63][64]

Prevention

There is a significant relation between lifestyle (including food consumption) and cancer prevention.[65] Exercise and diet may help prevent prostate cancer to the same extent as may medications such as alpha-blockers and 5-alpha-reductase inhibitors.

Medications

Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride[66] and dutasteride,[67] have also shown some promise. The use of these medications for primary prevention is still in the testing phase, and they are not widely used for this purpose. A 2008 study found that finasteride reduces the incidence of prostate cancer by 30%, without any increase in the risk of High-Grade prostate cancer.[68] 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.[68]

Compared to placebo treatment, taking 5-alpha-reductase inhibitors (5-ARIs) can reduce a man’s risk of being diagnosed with prostate cancer from around 5–9% to around 4-6% during up to 7 years of treatment, according to a Cochrane Review of studies.[69]

Ejaculation frequency

More frequent ejaculation also may decrease a man's risk of prostate cancer. One study showed that men who ejaculated 3-5 times a week at the age of 15-19 had a decreased rate of prostate cancer when they are old, though other studies have shown no benefit.[70][71] The results contradict those of previous studies, which have suggested that having had many sexual partners, or a high frequency of sexual activity, increases the risk of prostate cancer by up to 40 percent. A key difference may be that these earlier studies defined sexual activity as sexual intercourse, whereas this study focused on the number of ejaculations, whether or not intercourse was involved.[72] Another study completed in 2004 reported that "Most categories of ejaculation frequency were unrelated to risk of prostate cancer. However, high ejaculation frequency was related to decreased risk of total prostate cancer." The report abstract concluded, "Our results suggest that ejaculation frequency is not related to increased risk of prostate cancer."[73]

Diet

Consuming fish appears to lower prostate cancer deaths but not the occurrence of prostate cancer.[74] Omega-3 fatty acids are unlikely to prevent prostate cancer.[75] There is no evidence that vitamin supplements affect risk.[76] Trans fats may be associated with an increased risk of cancer but the evidence is still limited.[77] The American Dietetic Association and Dieticians of Canada report a decreased incidence of prostate cancer for those following a vegetarian diet.[78]

Management

Main article: Management of 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.[79][80][81] William J. Catalona, MD: regarding Active Surveillance, "Watchful Waiting or for some patients, Wishful Waiting: Can delay prompt treatment of life-threatening tumors, it would require repeated biopsies that often make subsequent nerve-sparing surgery more difficult and it causes many patients anxiety about living with untreated cancer, thus diminishing their quality of life." These men may have already been chemically castrated and impotent.

Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are age, general health, and patient views about potential treatments and their possible side-effects. Because all 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. 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.[82][83][84]

Although the widespread use of prostate specific antigen (PSA) screening in the USA has resulted in diagnosis at earlier age and cancer stage, the vast majority of cases are still diagnosed in men older than 65 years, and approximately 25% of cases are diagnosed in men older than 75 years.[85] Though US National Comprehensive Cancer Network guidelines [86] recommend using life expectancy greater than or less than 10 years to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as radical prostatectomy (RP) or radiation therapy and are instead treated with hormonal therapy or watchful waiting. This pattern can be attributed to factors such as medical co-morbidity and patient preferences is regard to quality of life in addition to prostate cancer specific risk factors such as pretreatment PSA, Gleason score and clinical stage. As the average life expectancy increases due to advances in treatment of cardiovascular, pulmonary and other chronic disease, it is likely that more elderly patients will be living long enough to suffer the consequences of their prostate cancer. Therefore, there is currently much interest in the role of aggressive prostate cancer treatment modalities such as with surgery or radiation in the elderly population who have localized disease. The results of one randomized controlled trial published by the Scandinavian Prostate Cancer Group 4 [87] evaluated cancer-specific mortality in patients treated with RP compared with watchful waiting. The patients receiving radical prostatectomy had a relative risk reduction of 30.7% [95% confidence interval 2.5%-50.7%], but an absolute risk reduction of 6% [95% confidence interval 0.5%-11.5%]. The number needed to treat was calculated to be 16. This means that, over the median follow up period of approximately 10 years, 16 patients with localized prostate cancer would need to receive radical prostatectomy rather than watchful waiting in order to prevent one death due to prostate cancer. Further subset analysis revealed that this benefit did not apply to all ages equally. In men younger than 65 years, patients randomized to receive radical prostatectomy actually had a 10-18% absolute risk reduction in cancer-specific mortality compared to those randomized to watchful waiting. However, in men older than 65, there was no statistically significant risk reduction even when adjusted for PSA level, Gleason score and tumor stage. Randomized, controlled trials comparing radical prostatectomy, radiation therapy, hormonal therapy and watchful waiting would provide the best evidence for how to best treat elderly patients. Such trials are urgently needed, as the elderly population is rapidly growing and is expected to continue to do so. Study results in 2011 suggest active surveillance is the best choice for older 'low-risk' patients.[88]

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.[89] 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.[90]

Castration-resistant prostate cancer

Most hormone dependent cancers become refractory after one to three years and resume growth despite hormone therapy. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term castration-resistant has replaced "hormone refractory" because while they are no longer responsive to castration treatment (reduction of available androgen/testosterone/DHT by chemical or surgical means), these cancers still show reliance upon hormones for androgen receptor activation.[91] Before 2004, all treatments for castration-resistant prostate cancer (CRPC) were considered[who?] palliative and not shown to prolong survival.[citation needed] However, there are now several treatments available to treat CRPC that improve survival.

The cancer chemotherapic docetaxel, has been used as treatment for (CRPC) with a median survival benefit of 2 to 3 months.[92][93] Docetaxel's FDA approval in 2004 was significant as it was the first treatment proven to prolong survival in CRPC. In 2010, the FDA approved a second-line chemotherapy treatment known as cabazitaxel.[94]

Off-label use of the oral drug, Ketoconazole, is sometimes used as a way to further manipulate hormones with a therapeutic effect in CRPC. However, many side effects are possible with this drug and abiraterone is likely to supplant usage since it has a similar mechanism of action with less toxic side effects.

A combination of bevacizumab (Avastin), docetaxel (taxotere), thalidomide and prednisone appears effective in the treatment of CRPC.[95]

The immunotherapy treatment, sipuleucel-T, is also effective in the treatment of CRPC with a median survival benefit of 4 months.[96]

The second line hormonal therapy, abiraterone, completed a phase 3 trial for CRPC patients who have failed chemotherapy in 2010. Results were positive. Overall survival increased by 4.6 months when compared to placebo. On April 28, 2011, the U.S. Food and Drug Administration approved abiraterone acetate in combination with prednisone to treat patients with late-stage (metastatic) castration-resistant prostate cancer who have received prior docetaxel (chemotherapy).[citation needed] On 19th August 2011, the BBC reported the possibility that Abdelbaset al-Megrahi is being kept alive with abiraterone.[97] Professor Roger Kirby stated: "Unfortunately I don't think they were aware of these new treatments such as abiraterone, which is transforming the prospects for patients with advanced prostate cancer. They just are living longer and longer. It's unknown how long this man will live and with extra additional new treatments it could have been predicted that he might be alive."[98]

Alpharadin completed a phase 3 trial for CRPC patients with bone metastasis. A pre-planned interim analysis showed improved survival and quality of life. The study was stopped for ethical reasons to give the placebo group the same treatment. Apharadin uses bone targeted Radium-223 isotopes to kill cancer cells by alpha radiation. Alpharadin is an investigational agent and is not approved for marketing by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), or any other health authorities.[99]

There are also several treatments currently in clinical trials to treat CRPC. These include the 2nd generation hormonal therapies MDV3100 and orteronel (TAK-700), the immunotherapy PROSTVAC, and the bone metastasis-targeting cabozantinib (XL-184).

Prognosis

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 who 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.[100]) 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 men from the United States. Prostate cancer affected eighteen percent of American men and caused death in three percent in 2005.[101] In Japan, death from prostate cancer was one-fifth to one-half the rates in the United States and Europe in the 1990s.[102] In India in the 1990s, half of the people with prostate cancer confined to the prostate died within ten years.[103] African-American men have 50–60 times more prostate cancer and prostate cancer deaths than men in Shanghai, China.[104] In Nigeria, two percent of men develop prostate cancer, and 64% of them are dead after two years.[105]

In patients who 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.[106]

In 1941, Charles Huggins reported that androgen ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer.[107] He was awarded the 1966 Nobel Prize for Physiology or Medicine for this discovery. 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.[108] 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.[109]

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 three 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 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;[110] the SEARCH registry, representing data from several Veterans Administration and active military medical centers;[111] a multi-institutional cohort in Germany;[112] and the prostatectomy cohort at Johns Hopkins University.[113] More recently, it has been shown to predict metastasis and mortality following prostatectomy, radiation therapy, watchful waiting, or androgen deprivation therapy.[114]

Epidemiology

Age-standardized death from prostate cancer per 100,000 inhabitants in 2004.[115]
  no data
  less than 4
  4-8
  8-12
  12-16
  16-20
  20-24
  24-28
  28-32
  32-36
  36-40
  40-44
  more than 44

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.[2] 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.[116][117] 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.[116][117][118] However, these high rates may be affected by increasing rates of detection.[119] Many suggest that prostate cancer may be under reported, yet BPH incidence in China and Japan is similar to rates in Western countries.,[120][121]

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.[122] 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 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.[68][123]

More than 80% of men will develop prostate cancer by the age of 80.[124] However, in the majority of cases, it will be slow-growing and harmless. In such men, diagnosing prostate cancer is overdiagnosis—the needless identification of a technically aberrant condition that will never harm the patient—and treatment in such men exposes them to all of the adverse effects, with no possibility of extending their lives.[125]

History

Although the prostate was first described by Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538, prostate cancer was not identified until 1853.[126] 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.[127] Removal of the entire gland (radical perineal prostatectomy) was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital.[128] 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.[129] 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.[130] 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.[131][132]

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.[133]

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.[134]

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.[135]

Society and culture

Discrimination

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.[136] In 2001 The Guardian noted that Britain had 3,000 nurses specializing in breast cancer, compared to only one for prostate cancer. It also discovered that the waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer.[137] A 2007 report by The National Prostate Cancer Coalition stated that for every prostate cancer drug on the market, there were seven used to treat breast cancer. 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.[136][138] Equality campaigners such as author Warren Farrell cite such stark spending inequalities as a clear example of governments unfairly favouring women's health over men's health.[139]

Disparities also extend into areas such as detection, with governments failing to fund or mandate prostate cancer screening whilst 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.[140][141] Prostate cancer also experiences significantly less media coverage than other, equally prevalent cancers, with a study by Prostate Coalition showing 2.6 breast cancer stories for each one covering cancer of the prostate.[136]

Prostate cancer awareness month

Prostate cancer awareness month takes place in September in a number of countries. A blue ribbon is used to promote the cause.[142][143]

Research

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.[144][145] 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 catechins, 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.[146]

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).[147] Altered expression of IGF axis members has been implicated in the development of many different types of cancers, including prostate.[148][149]

A genistein derivative KBU2046 is under investigation for prostate cancer.[150] MDV3100 is in phase III trials for HRPC (chemo-naive and post-chemo patient populations).[151]

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.[152][153] 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.[154][155][156]

Diagnosis

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.[157]

EN2

Presence of the EN2 (gene) in urine has been correlated to a high probability of prostate cancer.[1]

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 fluid massaged from the prostate by the doctor and first-void urinated out within a limited amount of urine into the specimen container. 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. Although not a replacement for serum PSA level, the PCA3 test is an additional tool 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 really needed. The higher the expression of PCA3 in the sample, 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 research is being conducted on 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.[158][159]

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.[160]

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.[161]

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.[162]

References

  1. ^ "ACS :: What Is Prostate Cancer?" American Cancer Society :: Information and Resources for Cancer: Breast, Colon, Prostate, Lung and Other Forms. Web. 15 June 2010. "?". Retrieved 9 August 2010.
  2. ^ a b "IARC Worldwide Cancer Incidence Statistics—Prostate". JNCI Cancer Spectrum. Oxford University Press. December 19, 2001. Archived from the original on February 5, 2006. Retrieved on 5 April 2007 through the Internet Archive
  3. ^ Sam Lister (February 11, 2009). "Urine test could speed treatment of prostate cancer". The Sunday Times. Retrieved 9 August 2010.
  4. ^ a b Djulbegovic M, Beyth RJ, Neuberger MM; et al. (2010). "Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials". BMJ. 341: c4543. doi:10.1136/bmj.c4543. PMC 2939952. PMID 20843937. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  5. ^ Aumüller, G. (1979). Prostate Gland and Seminal Vesicles. Berlin-Heidelberg: Springer-Verlag.
  6. ^ Moore, K. (1999). Clinically Oriented Anatomy. Baltimore, Maryland: Lippincott Williams & Wilkins. ISBN 0683061321. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Steive, H. (1930). "Männliche Genitalorgane". Handbuch der mikroskopischen Anatomie des Menschen. Vol. VII Part 2. Berlin: Springer. pp. 1–399.
  8. ^ BMJ Group (8 December 2009). "Prostate cancer: How far has your cancer spread? The TNM system". Guardian.co.uk. Retrieved 9 August 2010.
  9. ^ Miller DC, Hafez KS, Stewart A, Montie JE, Wei JT (2003). "Prostate carcinoma presentation, diagnosis, and staging: an update form the National Cancer Data Base". Cancer. 98 (6): 1169–78. doi:10.1002/cncr.11635. PMID 12973840. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ van der Cruijsen-Koeter, IW (2005). "Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer, section rotterdam". Urol. 174 (1): 121–5. doi:10.1097/01.ju.0000162061.40533.0f. PMID 15947595. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  11. ^ Hsing AW, Chokkalingam AP (2006). "Prostate cancer epidemiology". Frontiers in Bioscience. 11: 1388–413. doi:10.2741/1891. PMID 16368524.
  12. ^ Hankey, BF (1999). "Cancer surveillance series: interpreting trends in prostate cancer—part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates". J Natl Cancer Inst. 91 (12): 1017–24. doi:10.1093/jnci/91.12.1017. PMID 10379964. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  13. ^ Breslow, N (1977). "Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France". Int J Cancer. 20 (5): 680–8. doi:10.1002/ijc.2910200506. PMID 924691. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  14. ^ Zeegers MP; Jellema, A; Ostrer, H (2003). "Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma: a meta-analysis". Cancer. 97 (8): 1894–903. doi:10.1002/cncr.11262. PMID 12673715.
  15. ^ Jemal A, A (2005). "Cancer statistics, 2005". CA Cancer J Clin. 55 (1): 10–30. doi:10.3322/canjclin.55.1.10. PMID 15661684. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help) Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259
  16. ^ Martin RM, Vatten L, Gunnell D, Romundstad P (2010). "Blood pressure and risk of prostate cancer: cohort Norway (CONOR)". Cancer Causes Control. 21 (3): 463–72. doi:10.1007/s10552-009-9477-x. PMID 19949849. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Witte ON; et al. (2010). "Growth Regulation of Hematopoietic and Epithelial Cancers and the Immune Response". Science. 329 (5991): 568–571. doi:10.1126/science.1189992. PMC 2917982. PMID 20671189. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  18. ^ Steinberg GD, Carter BS, Beaty TH, Childs B, Walsh PC (1990). "Family history and the risk of prostate cancer". Prostate. 17 (4): 337–47. doi:10.1002/pros.2990170409. PMID 2251225.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ a b Gallagher RP, Fleshner N (1998). "Prostate cancer: 3. Individual risk factors" (PDF). CMAJ. 159 (7): 807–13. PMC 1232741. PMID 9805030. {{cite journal}}: Unknown parameter |month= ignored (help)
  20. ^ Hoffman RM, Gilliland FD, Eley JW, Harlan LC, Stephenson RA, Stanford JL, Albertson PC, Hamilton AS, Hunt WC, Potosky AL (2001). "Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study". J. Natl. Cancer Inst. 93 (5): 388–95. doi:10.1093/jnci/93.5.388. PMID 11238701. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  21. ^ Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (2000). "Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland". N. Engl. J. Med. 343 (2): 78–85. doi:10.1056/NEJM200007133430201. PMID 10891514. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA (1997). "The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews". N. Engl. J. Med. 336 (20): 1401–8. doi:10.1056/NEJM199705153362001. PMID 9145676. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Beuzeboc P, Soulié M, Richaud P, Salomon L, Staerman F, Peyromaure M, Mongiat-Artus P, Cornud F, Paparel P, Davin JL, Molinié V (2009). "[Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives]". Prog. Urol. (in French). 19 (11): 819–24. doi:10.1016/j.purol.2009.06.002. PMID 19945666. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ "Scientists Discover Anti-Cancer Mechanism that Arrests Early Prostate Cancer". August 4, 2005.
  25. ^ Venkateswaran, V (2010 Aug). "Diet and prostate cancer: mechanisms of action and implications for chemoprevention". Nature reviews. Urology. 7 (8): 442–53. PMID 20647991. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  26. ^ Key, TJ (2011-01-04). "Fruit and vegetables and cancer risk". British journal of cancer. 104 (1): 6–11. PMID 21119663.
  27. ^ Alexander, DD (2010-11-02). "A review and meta-analysis of prospective studies of red and processed meat intake and prostate cancer". Nutrition journal. 9: 50. PMID 21044319. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  28. ^ Wigle DT, Turner MC, Gomes J, Parent ME (2008). "Role of hormonal and other factors in human prostate cancer". Journal of Toxicology and Environmental Health. Part B, Critical Reviews. 11 (3–4): 242–59. doi:10.1080/10937400701873548. PMID 18368555. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  29. ^ Schulman, CC (2001). "Nutrition and prostate cancer: evidence or suspicion?". Urology. 58 (3): 318–34. doi:10.1016/S0090-4295(01)01262-6. PMID 11549473. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  30. ^ Lee AH, Fraser ML, Meng X, Binns CW (2006). "Protective effects of green tea against prostate cancer". Expert Rev Anticancer Ther. 6 (4): 507–13. doi:10.1586/14737140.6.4.507. PMID 16613539. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  31. ^ Kikuchi N, Ohmori K, Shimazu T, Nakaya N, Kuriyama S, Nishino Y, Tsubono Y, Tsuji I (2006). "No association between green tea and prostate cancer risk in Japanese men: the Ohsaki Cohort Study". Br. J. Cancer. 95 (3): 371–3. doi:10.1038/sj.bjc.6603230. PMC 2360636. PMID 16804523. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ Katz, Aaron (2006). Guide to Prostate Health: From Conventional to Holistic Therapies. Freedom Press. ISBN 1-893910-37-7. {{cite book}}: Check |authorlink= value (help); External link in |authorlink= (help)
  33. ^ "Multivitamin prostate warning". Health. BBC NEWS. 16 May 2007.
  34. ^ Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, Leitzmann MF (2007). "Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study". J. Natl. Cancer Inst. 99 (10): 754–64. doi:10.1093/jnci/djk177. PMID 17505071. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  35. ^ a b c d Figueiredo JC, Grau MV, Haile RW, Sandler RS, Summers RW, Bresalier RS, Burke CA, McKeown-Eyssen GE, Baron JA (2009). "Folic acid and risk of prostate cancer: results from a randomized clinical trial". J. Natl. Cancer Inst. 101 (6): 432–5. doi:10.1093/jnci/djp019. PMC 2657096. PMID 19276452. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  36. ^ a b c d e f Shannon J, Phoutrides E, Palma A, Farris P, Peters L, Forester A, Tillotson CJ, Garzotto M (2009). "Folate intake and prostate cancer risk: a case-control study". Nutr Cancer. 61 (5): 617–28. doi:10.1080/01635580902846593. PMID 19838935.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ Jacobs EJ, Rodriguez C, Mondul AM, Connell CJ, Henley SJ, Calle EE, Thun MJ (2005). "A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence". J. Natl. Cancer Inst. 97 (13): 975–80. doi:10.1093/jnci/dji173. PMID 15998950. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ Shannon J, Tewoderos S, Garzotto M, Beer TM, Derenick R, Palma A, Farris PE (2005). "Statins and prostate cancer risk: a case-control study". Am. J. Epidemiol. 162 (4): 318–25. doi:10.1093/aje/kwi203. PMID 16014776. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  39. ^ Dennis LK, Lynch CF, Torner JC (2002). "Epidemiologic association between prostatitis and prostate cancer". Urology. 60 (1): 78–83. doi:10.1016/S0090-4295(02)01637-0. PMID 12100928. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  40. ^ Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003). "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults". N. Engl. J. Med. 348 (17): 1625–38. doi:10.1056/NEJMoa021423. PMID 12711737. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  41. ^ Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ (1996). "Prospective study of sex hormone levels and risk of prostate cancer". J. Natl. Cancer Inst. 88 (16): 1118–26. doi:10.1093/jnci/88.16.1118. PMID 8757191. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  42. ^ "?". Retrieved 9 August 2010.
  43. ^ "Veterans exposed to Agent Orange have higher rates of prostate cancer recurrence". Medical College of Georgia News. May 20, 2007.
  44. ^ Urisman A, Molinaro RJ, Fischer N, Plummer SJ, Casey G, Klein EA, Malathi K, Magi-Galluzzi C, Tubbs RR, Ganem D, Silverman RH, DeRisi JL (2006). "Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant". PLoS Pathog. 2 (3): e25. doi:10.1371/journal.ppat.0020025. PMC 1434790. PMID 16609730. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  45. ^ Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR (2009). "XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors". Proc. Natl. Acad. Sci. U.S.A. 106 (38): 16351–6. doi:10.1073/pnas.0906922106. PMC 2739868. PMID 19805305. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  46. ^ Hohn O, Krause H, Barbarotto P, Niederstadt L, Beimforde N, Denner J, Miller K, Kurth R, Bannert N (2009). "Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients". Retrovirology. 6: 92. doi:10.1186/1742-4690-6-92. PMC 2770519. PMID 19835577.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  47. ^ "Male Genitals - Prostate Neoplasms". Pathology study images. University of Virginia School of Medicine. Archived from the original on 2011-04-28. Retrieved 2011-04-28. There are many connections between the prostatic venous plexus and the vertebral veins. The veins forming the prostatic plexus do not contain valves and it is thought that straining to urinate causes prostatic venous blood to flow in a reverse direction and enter the vertebral veins carrying malignant cells to the vertebral column.
  48. ^ Journal-molecular cancer, review, 2006 5:17, doi:10.1186/1476-4598-5-17
  49. ^ Leav I, Plescia J, Goel HL, Li J, Jiang Z, Cohen RJ, Languino LR, Altieri DC (2010). "Cytoprotective mitochondrial chaperone TRAP-1 as a novel molecular target in localized and metastatic prostate cancer". Am. J. Pathol. 176 (1): 393–401. doi:10.2353/ajpath.2010.090521. PMC 2797899. PMID 19948822. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  50. ^ Zha J, Huang YF (2009). "[TGF-beta/Smad in prostate cancer: an update]". Zhonghua Nan Ke Xue (in Chinese). 15 (9): 840–3. PMID 19947572. {{cite journal}}: Unknown parameter |month= ignored (help)
  51. ^ Watanabe SI, Miyata Y, Kanda S, Iwata T, Hayashi T, Kanetake H, Sakai H (2009). "Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy". J Cancer Res Clin Oncol. 136 (5): 787–93. doi:10.1007/s00432-009-0718-x. PMID 19946707. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  52. ^ Senapati S, Rachagani S, Chaudhary K, Johansson SL, Singh RK, Batra SK (2010). "Overexpression of macrophage inhibitory cytokine-1 induces metastasis of human prostate cancer cells through the [[FAK-RhoA]] signaling pathway". Oncogene. 29 (9): 1293–302. doi:10.1038/onc.2009.420. PMC 2896817. PMID 19946339. {{cite journal}}: URL–wikilink conflict (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  53. ^ Narizhneva NV, Tararova ND, Ryabokon P, Shyshynova I, Prokvolit A, Komarov PG, Purmal AA, Gudkov AV, Gurova KV (2009). "Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer". Cell Cycle. 8 (24): 4155–67. doi:10.4161/cc.8.24.10316. PMC 2896895. PMID 19946220. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  54. ^ Yao V, Berkman CE, Choi JK, O'Keefe DS, Bacich DJ (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". Prostate. 70 (3): 305–16. doi:10.1002/pros.21065. PMID 19830782. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  55. ^ Essink-Bot ML, de Koning HJ, Nijs HG, Kirkels WJ, van der Maas PJ, Schröder FH (1998). "Short-term effects of population-based screening for prostate cancer on health-related quality of life". J. Natl. Cancer Inst. 90 (12): 925–31. doi:10.1093/jnci/90.12.925. PMID 9637143. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  56. ^ Chuang AY, DeMarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI (2007). "Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma". Am. J. Surg. Pathol. 31 (8): 1246–55. doi:10.1097/PAS.0b013e31802f5d33. PMID 17667550. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ a b Nutting C, Horwich A, Fisher C, Parsons C, Dearnaley DP (1997). "Small-cell carcinoma of the prostate". Journal of the Royal Society of Medicine. 90 (6): 340–1. PMC 1296316. PMID 9227387. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  58. ^ a b Wei ZF, Xu H, Wang H, Wei W, Cheng W, Zhou WQ, Ge JP, Zhang ZY, Gao JP, Yin HL (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. PMID 19947569. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  59. ^ Biomarker for Prostate Cancer
  60. ^ Catz SD, Johnson JL (2003). "BCL-2 in prostate cancer: a minireview". Apoptosis. 8 (1): 29–37. doi:10.1023/A:1021692801278. PMID 12510149. {{cite journal}}: Unknown parameter |month= ignored (help)
  61. ^ Srikumar Chakravarthi, David Low Wee Yang, Thanikachalam P, Nagaraja HS, Nadeem Irfan Bukhari (2009). "Assessment of proliferative index and its association with Ki-67 antigen molecule expression in nodular hyperplasia of prostate". Indian Journal of Science & Technology. 2 (8): 1–4. ISSN 0974-6846.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  62. ^ British Journal of Cancer - 15 Feb 2011
  63. ^ Prostate Cancer Screening CDC, updated April 6, 2010
  64. ^ "Untreated prostate cancer no death sentence", Reuters, June 18, 2010
  65. ^ Wiseman, M (2008 Aug). "The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective". The Proceedings of the Nutrition Society. 67 (3): 253–6. PMID 18452640. {{cite journal}}: Check date values in: |date= (help)
  66. ^ Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA (2003). "The influence of finasteride on the development of prostate cancer". N. Engl. J. Med. 349 (3): 215–24. doi:10.1056/NEJMoa030660. PMID 12824459. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  67. ^ Andriole GL, Roehrborn C, Schulman C, Slawin KM, Somerville M, Rittmaster RS (2004). "Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia". Urology. 64 (3): 537–41, discussion 542–3. doi:10.1016/j.urology.2004.04.084. PMID 15351586. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  68. ^ a b c Redman MW, Tangen CM, Goodman PJ, Lucia MS, Coltman CA, Thompson IM (2008). "Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach". Cancer Prev Res (Phila Pa). 1 (3): 174–81. doi:10.1158/1940-6207.CAPR-08-0092. PMC 2844801. PMID 19138953. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  69. ^ Wilt T, MacDonald R, Hagerty K, Schellhammer P, Kramer BS. 5-alpha-reductase inhibitors for prostate cancer prevention. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007091. DOI: 10.1002/14651858.CD007091 http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD007091/frame.html
  70. ^ Giles GG, Severi G, English DR, McCredie MR, Borland R, Boyle P, Hopper JL (2003). "Sexual factors and prostate cancer". BJU Int. 92 (3): 211–6. doi:10.1046/j.1464-410X.2003.04319.x. PMID 12887469. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  71. ^ Leitzmann MF, Platz EA, Stampfer MJ, Willett WC, Giovannucci E (2004). "Ejaculation frequency and subsequent risk of prostate cancer". JAMA. 291 (13): 1578–86. doi:10.1001/jama.291.13.1578. PMID 15069045. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  72. ^ Douglas Fox (16 July 2003). "Masturbating may protect against prostate cancer". New Scientist.
  73. ^ Dimitropoulou P, Lophatananon A, Easton D, Pocock R, Dearnaley DP, Guy M, Edwards S, O'Brien L, Hall A, Wilkinson R, Eeles R, Muir KR (2009). "Sexual activity and prostate cancer risk in men diagnosed at a younger age". BJU Int. 103 (2): 178–85. doi:10.1111/j.1464-410X.2008.08030.x. PMID 19016689. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  74. ^ Szymanski, KM (2010 Nov). "Fish consumption and prostate cancer risk: a review and meta-analysis". The American journal of clinical nutrition. 92 (5): 1223–33. PMID 20844069. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  75. ^ MacLean, CH (2006-01-25). "Effects of omega-3 fatty acids on cancer risk: a systematic review". JAMA : the journal of the American Medical Association. 295 (4): 403–15. doi:10.1001/jama.295.4.403. PMID 16434631. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  76. ^ . PMID 21273283. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  77. ^ Thompson, AK (2008 Dec). "Trans-fatty acids and cancer: the evidence reviewed". Nutrition research reviews. 21 (2): 174–88. PMID 19087370. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  78. ^ American Dietetic Association and Dieticians of Canada (2003). "Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets". Journal of the American Dietetic Association. 103 (6): 748–65. doi:10.1053/jada.2003.50142. PMID 12778049. {{cite journal}}: Unknown parameter |month= ignored (help)
  79. ^ Hong H, Zhang Y, Sun J, Cai W (2009). "Positron emission tomography imaging of prostate cancer". Amino Acids. 39 (1): 11–27. doi:10.1007/s00726-009-0394-9. PMC 2883014. PMID 19946787. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  80. ^ Braun K, Ehemann V, Wiessler M, Pipkorn R, Didinger B, Mueller G, Waldeck W (2009). "High-resolution flow cytometry: a suitable tool for monitoring aneuploid prostate cancer cells after TMZ and TMZ-BioShuttle treatment". Int J Med Sci. 6 (6): 338–47. PMC 2781174. PMID 19946604.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  81. ^ Peyromaure M, Valéri A, Rebillard X, Beuzeboc P, Richaud P, Soulié M, Salomon L (2009). "[Characteristics of prostate cancer in men less than 50-year-old]". Prog. Urol. (in French). 19 (11): 803–9. doi:10.1016/j.purol.2009.04.010. PMID 19945663. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  82. ^ Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, Barry MJ, Zietman A, O'Leary M, Walker-Corkery E, Yao SL (2009). "Outcomes of Localized Prostate Cancer Following Conservative Management". The Journal of the American Medical Association. 302 (11): 1202–09. doi:10.1001/jama.2009.1348. PMC 2822438. PMID 19755699. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  83. ^ Mongiat-Artus P, Peyromaure M, Richaud P, Droz JP, Rainfray M, Jeandel C, Rebillard X, Moreau JL, Davin JL, Salomon L, Soulié M (2009). "[Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French association of urology]". Prog. Urol. (in French). 19 (11): 810–7. doi:10.1016/j.purol.2009.02.008. PMID 19945664. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  84. ^ Picard JC, Golshayan AR, Marshall DT, Opfermann KJ, Keane TE (2009). "The multi-disciplinary management of high-risk prostate cancer". Urol. Oncol. doi:10.1016/j.urolonc.2009.09.002. PMID 19945310. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  85. ^ Fitzpatrick, JM (2008). "Management of localized prostate cancer in senior adults: the crucial role of comorbidity". BJU international. 101 Suppl 2: 16–22. doi:10.1111/j.1464-410X.2007.07487.x. PMID 18307688.
  86. ^ National Comprehensive Cancer Network http://www.nccn.org/index.asp. Retrieved 2011-03-22. {{cite web}}: Missing or empty |title= (help)
  87. ^ Bill-Axelson, A; Holmberg, L; Filén, F; Ruutu, M; Garmo, H; Busch, C; Nordling, S; Häggman, M; Andersson, SO (2008). "Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial". Journal of the National Cancer Institute. 100 (16): 1144–54. doi:10.1093/jnci/djn255. PMC 2518167. PMID 18695132.
  88. ^ http://www.cancer.gov/ncicancerbulletin/041911/page2 Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer
  89. ^ Mouraviev V, Evans B, Polascik TJ (2006). "Salvage prostate cryoablation after primary interstitial brachytherapy failure: a feasible approach". Prostate Cancer Prostatic Dis. 9 (1): 99–101. doi:10.1038/sj.pcan.4500853. PMID 16314889.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  90. ^ "Prostate Cancer At A Glance". ShaveMagazine.com. {{cite web}}: External link in |publisher= (help)
  91. ^ Seruga B, Ocana A, Tannock IF (2011). "Drug resistance in metastatic castration-resistant prostate cancer". Nat Rev Clin Oncol. 8 (1): 12–23. doi:10.1038/nrclinonc.2010.136. PMID 20859283. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  92. ^ Clarke NW (2005?). "Docetaxel for the Treatment of Hormone Refractory Prostate Cancer" (PDF). {{cite web}}: Check date values in: |year= (help)CS1 maint: year (link)
  93. ^ "Prostate cancer (hormone-refractory) - docetaxel". National Institute for Health and Clinical Excellence. 2010-12-10. Retrieved 2011-07-04.
  94. ^ de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO (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. PMID 20888992. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  95. ^ "Avastin®, Thalomid®, Taxotere®, and Prednisone Effective for Men with Hormone Refractory Prostate Cancer". March 2010. Retrieved 10 May 2010.
  96. ^ Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF (2010). "Sipuleucel-T immunotherapy for castration-resistant prostate cancer". N. Engl. J. Med. 363 (5): 411–22. doi:10.1056/NEJMoa1001294. PMID 20818862. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  97. ^ Cancer Research UK
  98. ^ BBC Online
  99. ^ "Positive Outcome of Interim Analysis of pivotal Alpharadin study: Primary endpoint met in Phase III ALSYMPCA study". Press Release. Algeta.com. 2011-06-06. Retrieved 2011-07-04.
  100. ^ ACS :: What Are The Risk Factors for Prostate Cancer?
  101. ^ Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005). "Cancer statistics, 2005". CA Cancer J Clin. 55 (1): 10–30. doi:10.3322/canjclin.55.1.10. PMID 15661684.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  102. ^ Wakai K (2005). "[Descriptive epidemiology of prostate cancer in Japan and Western countries]". Nippon Rinsho (in Japanese). 63 (2): 207–12. PMID 15714967. {{cite journal}}: Unknown parameter |month= ignored (help)
  103. ^ Jaubert de Beaujeu M, Chavrier Y (1976). "[Deformations of the anterior thoracic wall (author's transl)]". Ann Chir Thorac Cardiovasc (in French). 15 (1): 1–6. PMID 1259345. {{cite journal}}: Unknown parameter |month= ignored (help)
  104. ^ Hsing AW, Tsao L, Devesa SS (2000). "International trends and patterns of prostate cancer incidence and mortality". Int. J. Cancer. 85 (1): 60–7. doi:10.1002/(SICI)1097-0215(20000101)85:1<60::AID-IJC11>3.0.CO;2-B. PMID 10585584. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  105. ^ Osegbe DN (1997). "Prostate cancer in Nigerians: facts and nonfacts". J. Urol. 157 (4): 1340–3. doi:10.1016/S0022-5347(01)64966-8. PMID 9120935. {{cite journal}}: Unknown parameter |month= ignored (help)
  106. ^ Di Blasio CJ, Rhee AC, Cho D, Scardino PT, Kattan MW (2003). "Predicting clinical end points: treatment nomograms in prostate cancer". Semin. Oncol. 30 (5): 567–86. doi:10.1016/S0093-7754(03)00351-8. PMID 14571407. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  107. ^ Huggins C, Steven RE, Hodges CV (1941). "Studies on prostatic cancer". Arch. Surg. 43: 209–223.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  108. ^ Hellerstedt BA, Pienta KJ (2002). "The current state of hormonal therapy for prostate cancer". CA Cancer J Clin. 52 (3): 154–79. doi:10.3322/canjclin.52.3.154. PMID 12018929.
  109. ^ Feldman BJ, Feldman D (2001). "The development of androgen-independent prostate cancer". Nat. Rev. Cancer. 1 (1): 34–45. doi:10.1038/35094009. PMID 11900250. {{cite journal}}: Unknown parameter |month= ignored (help)
  110. ^ Cooperberg MR, Pasta DJ, Elkin EP; et al. (2005). "The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy". J. Urol. 173 (6): 1938–42. doi:10.1097/01.ju.0000158155.33890.e7. PMC 2948569. PMID 15879786. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  111. ^ Cooperberg MR, Freedland SJ, Pasta DJ; et al. (2006). "Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy". Cancer. 107 (10): 2384–91. doi:10.1002/cncr.22262. PMID 17039503. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  112. ^ May M, Knoll N, Siegsmund M; et al. (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". J. Urol. 178 (5): 1957–62, discussion 1962. doi:10.1016/j.juro.2007.07.043. PMID 17868719. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  113. ^ Zhao KH, Hernandez DJ, Han M, Humphreys EB, Mangold LA, Partin AW (2008). "External validation of University of California, San Francisco, Cancer of the Prostate Risk Assessment score". Urology. 72 (2): 396–400. doi:10.1016/j.urology.2007.11.165. PMID 18372031. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  114. ^ Cooperberg MR, Broering JM, Carroll PR (2009). "Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis". J. Natl. Cancer Inst. 101 (12): 878–87. doi:10.1093/jnci/djp122. PMC 2697208. PMID 19509351. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  115. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov. 11, 2009. {{cite web}}: Check date values in: |accessdate= (help)
  116. ^ a b Overview: Prostate Cancer—What Causes Prostate Cancer? American Cancer Society (2 May 2006). Retrieved on 5 April 2007
  117. ^ a b Prostate Cancer FAQs. State University of New York School of Medicine Department of Urology (31 August 2006). Retrieved on 5 April 2007
  118. ^ Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW (2003). "Soy and isoflavone consumption in relation to prostate cancer risk in China". Cancer Epidemiol Biomarkers Prev. 12 (7): 665–8. PMID 12869409. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  119. ^ Potosky AL, Miller BA, Albertsen PC, Kramer BS (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. PMID 7530782. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  120. ^ Hanno P.M., Malcowicz S. B., Wein A. J., "Clinical Manual of Urology" McGraw Hill 2001
  121. ^ Homma Y., Kawabe K., Tsukamoto T., Yamanaka H., Okada K., Okajima E., Yoshida O., Kumazawa J., Fang-Liu G.; et al. (1997). "Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score". International Journal of Urology. 4 (1): 40–46. doi:10.1111/j.1442-2042.1997.tb00138.x. PMID 9179665. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  122. ^ Ahmedin J; et al. (2008). "Cancer Statistics, 2008". CA Cancer J Clin. 58 (2): 71–96. doi:10.3322/CA.2007.0010. PMID 18287387. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  123. ^ Gine Kolata (June 15, 2008). "New Take on a Prostate Drug, and a New Debate". NY Times. Retrieved 15 June 2008.
  124. ^ Bostwick, David G.; Eble, John N. (2007). Urological Surgical Pathology. St. Louis: Mosby. p. 468. ISBN 0-323-01970-6.
  125. ^ Woloshin, Steve; Schwartz, Lisa A. (2011). Overdiagnosed: Making People Sick in the Pursuit of Health. USA: Beacon Press. pp. 45–60. ISBN 0-8070-2200-4.{{cite book}}: CS1 maint: multiple names: authors list (link)
  126. ^ 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.[page needed]
  127. ^ Lytton B (2001). "Prostate cancer: a brief history and the discovery of hormonal ablation treatment". The Journal of Urology. 165 (6 Pt 1): 1859–62. doi:10.1016/S0022-5347(05)66228-3. PMID 11371867. {{cite journal}}: Unknown parameter |month= ignored (help)
  128. ^ Young HH (1905). "Four cases of radical prostatectomy". Johns Hopkins Bull. 16: 315.
  129. ^ Walsh PC, Lepor H, Eggleston JC (1983). "Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations". The Prostate. 4 (5): 473–85. doi:10.1002/pros.2990040506. PMID 6889192.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  130. ^ Huggins CB, Hodges CV (1941). "Studies on prostate cancer: 1. The effects of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate". Cancer Res. 1.[page needed]
  131. ^ Schally AV, Kastin AJ, Arimura A (1971). "Hypothalamic follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-regulating hormone: structure, physiology, and clinical studies". Fertility and Sterility. 22 (11): 703–21. PMID 4941683. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  132. ^ Tolis G, Ackman D, Stellos A; et al. (1982). "Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists". Proc. Natl. Acad. Sci. U.S.A. 79 (5): 1658–62. doi:10.1073/pnas.79.5.1658. PMC 346035. PMID 6461861. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  133. ^ Denmeade SR, Isaacs JT (2002). "A history of prostate cancer treatment". Nature Reviews. Cancer. 2 (5): 389–96. doi:10.1038/nrc801. PMID 12044015. {{cite journal}}: Unknown parameter |month= ignored (help)
  134. ^ Scott WW, Johnson DE, Schmidt JE; et al. (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. PMID 1104900. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  135. ^ Witte ON; et al. (2010). "Growth Regulation of Hematopoietic and Epithelial Cancers and the Immune Response". Science. 329 (5991): 568–571. doi:10.1126/science.1189992. PMC 2917982. PMID 20671189. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help); Unknown parameter |unused_data= ignored (help)
  136. ^ a b c A Gender Gap in Cancer
  137. ^ Cancer bias puts breasts first | Society | Society Guardian
  138. ^ Men lose out in battle for cancer cash - Times Online
  139. ^ http://books.google.co.uk/books?ei=K1nsTZi4CIOa8QOT1tm4AQ&ct=result&id=mRkqAAAAYAAJ&dq=prostate+cancer+misandry&q=prostate#search_anchor
  140. ^ http://www.timesonline.co.uk/tol/news/uk/article579050.ece
  141. ^ http://www.businessweek.com/technology/content/jun2007/tc20070612_953676.htm
  142. ^ http://dailycaller.com/2010/10/05/breast-cancer-receives-much-more-research-funding-publicity-than-prostate-cancer-despite-similar-number-of-victims/
  143. ^ http://www.msnbc.msn.com/id/7258393/ns/health-cancer/
  144. ^ Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S (2005). "Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice". Cancer Res. 65 (6): 2082–4. doi:10.1158/0008-5472.CAN-04-3992. PMID 15781616. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  145. ^ Chuu CP, Hiipakka RA, Kokontis JM, Fukuchi J, Chen RY, Liao S (2006). "Inhibition of tumor growth and progression of LNCaP prostate cancer cells in athymic mice by androgen and liver X receptor agonist". Cancer Res. 66 (13): 6482–6. doi:10.1158/0008-5472.CAN-06-0632. PMID 16818617. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  146. ^ Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H (2001). "Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10350–5. doi:10.1073/pnas.171326098. PMC 56964. PMID 11504910. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  147. ^ Grotendorst GR, Lau LF, Perbal B (2000). "CCN proteins are distinct from and should not be considered members of the insulin-like growth factor-binding protein superfamily". Endocrinology. 141 (6): 2254–6. doi:10.1210/en.141.6.2254. PMID 10830315. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  148. ^ Samani AA, Yakar S, LeRoith D, Brodt P (2007). "The role of the IGF system in cancer growth and metastasis: overview and recent insights". Endocrine Reviews. 28 (1): 20–47. doi:10.1210/er.2006-0001. PMID 16931767. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  149. ^ Jenkins PJ, Bustin SA (2004). "Evidence for a link between IGF-I and cancer". European Journal of Endocrinology. 151 (Suppl 1): S17–22. doi:10.1530/eje.0.151S017. PMID 15339239. {{cite journal}}: Unknown parameter |month= ignored (help)
  150. ^ Bergan at al. (16 Nov 2010). "Isoflavone-genistein derived drug, KBU2046, inhibits prostate tumor metastasis".
  151. ^ http://www.clinicaltrials.gov/ct2/results?intr=%22MDV3100%22 ClinicalTrials.gov listing of MDV3100 articles
  152. ^ Linja MJ, Savinainen KJ, Saramäki OR, Tammela TL, Vessella RL, Visakorpi T (2001). "Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer". Cancer Research. 61 (9): 3550–5. PMID 11325816. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  153. ^ Ford OH, Gregory CW, Kim D, Smitherman AB, Mohler JL (2003). "Androgen receptor gene amplification and protein expression in recurrent prostate cancer". The Journal of Urology. 170 (5): 1817–21. doi:10.1097/01.ju.0000091873.09677.f4. PMID 14532783. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  154. ^ Kokontis J, Takakura K, Hay N, Liao S (1994). "Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation". Cancer Research. 54 (6): 1566–73. PMID 7511045. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  155. ^ Umekita Y, Hiipakka RA, Kokontis JM, Liao S (1996). "Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride". Proc. Natl. Acad. Sci. U.S.A. 93 (21): 11802–7. doi:10.1073/pnas.93.21.11802. PMC 38139. PMID 8876218. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  156. ^ Kokontis JM, Hsu S, Chuu CP; et al. (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. PMID 16015608. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  157. ^ Iyer M, Salazar FB, Lewis X; et al. (2005). "Non-invasive imaging of a transgenic mouse model using a prostate-specific two-step transcriptional amplification strategy". Transgenic Res. 14 (1): 47–55. doi:10.1007/s11248-004-2836-1. PMID 15865048. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  158. ^ A Prostate Cancer Revolution. Newsweek, April 26, 2007.
  159. ^ Hansel DE, DeMarzo AM, Platz EA, Jadallah S, Hicks J, Epstein JI, Partin AW, Netto GJ (2007). "Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies". J. Urol. 177 (5): 1736–40. doi:10.1016/j.juro.2007.01.013. PMID 17437801. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  160. ^ van Weert HC, Pingen F (2009). "Recurrent thromboflebitis as a warning sign for cancer: a case report". Cases J. 2: 153. doi:10.1186/1757-1626-2-153. PMC 2783109. PMID 19946524.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  161. ^ Sartor AO, Hricak H, Wheeler TM, Coleman J, Penson DF, Carroll PR, Rubin MA, Scardino PT (2008). "Evaluating localized prostate cancer and identifying candidates for focal therapy". Urology. 72 (6 Suppl): S12–24. doi:10.1016/j.urology.2008.10.004. PMID 19095124. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  162. ^ Nilsson BO, Carlsson L, Larsson A, Ronquist G (2001). "Autoantibodies to prostasomes as new markers for prostate cancer". Ups. J. Med. Sci. 106 (1): 43–9. doi:10.3109/2000-1967-171. PMID 11817562.{{cite journal}}: CS1 maint: multiple names: authors list (link)

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