prostate cancerdisease characterized by uncontrolled growth of cells within the prostate gland, a walnut-sized organ surrounding the urethra just below the bladder in males. Worldwide among males, the incidence of prostate cancer is surpassed only by lung and stomach cancers; among North American men, only skin cancer occurs more often. Prostate cancer is rare in men below the age of 50, and in North America the disease is twice as common in black men as it is in whites. Prostate cancer should not be confused with benign prostate hyperplasia, which has similar symptoms and occurs often in older men but is not a type of cancer.
Causes and symptoms

The causes of prostate cancer are not clear. However, many cases of the disease appear to be related to aberrant cell signaling that involves male androgen hormones, particularly testosterone and its metabolites. Within certain tissues, testosterone may be converted into one of two active compounds—estradiol or dihydrotestosterone. Whereas estradiol promotes the growth of prostate cancer cells, dihydrotestosterone inhibits the programmed death (apoptosis) of those cells. Testosterone itself appears to play a central role in maintaining prostate cells and stimulating apoptosis when abnormal cells arise. However, the mechanism by which testosterone and its active derivatives contribute to the development of prostate cancer is not entirely understood.

The likelihood of a man’s developing prostate cancer doubles if a parent or sibling has had prostate cancer; this suggests that genetic factors play a role. Two genes, known as BRCA1 (breast cancer type 1) and BRCA2 (breast cancer type 2), have been linked to prostate cancer. As their names imply, they are commonly found in mutated forms in some women with breast cancer. However, studies have shown that men carrying mutations in BRCA2 have an increased risk of developing prostate cancer, and mutations in either gene can significantly reduce survival.

Several studies have revealed an association between hereditary susceptibility to prostate cancer and sequence variations in a gene called RNASEL (ribonuclease L), which plays a role in maintaining immunity against viral infections. The most common RNASEL variant is a mutation that results in decreased activity of the encoded ribonuclease L protein, thereby reducing immune defense against viruses. Men who inherit this mutation have a significant increase in risk of prostate cancer. Although mutations in RNASEL were initially suspected to increase susceptibility to infection by a virus called XMRV (xenotropic murine leukemia virus-related virus), which was found in prostate epithelial tissue in a small percentage of men with malignant prostate cancer, infection with the virus was later shown to also occur independently of RNASEL mutations. XMRV appears to be associated with aggressive forms of prostate cancer; however, the relationship between the virus and the pathogenesis of the disease is not clear. Failure of XMRV detection in some groups of European men with prostate cancer has raised important questions concerning XMRV’s presence in only certain populations.


When the prostate gland becomes cancerous, it can put pressure on the urethra, causing frequent or painful urination. Such pressure can also cause difficulty in urinating, a weak and intermittent urine flow, or blood in the urine. The cancerous growth may also put pressure on the nerves required for erection, causing impotence or sexual dysfunction. Other symptoms of prostate cancer include swollen lymph nodes in the groin and pain in the pelvis, hips, back, or ribs.


Prostate cancers usually grow very slowly, and individuals may not display symptoms for some time. If the prostate is enlarged, preliminary diagnosis can be made by rectal examination or transrectal ultrasound (TRUS). A blood test for prostate-specific antigen (PSA) is used to detect prostate tumours in their earliest stages. If any of these tests suggest cancer, a biopsy is done to confirm the diagnosis. When caught early, prostate cancer is treatable. A large majority of prostate cancers are diagnosed either before they have spread or when they have spread only locally. Survival rates in these cases are very high.




Other drugs, called antiandrogens, block the activity of androgens and are often used in combination with other forms of hormone therapy. An antiandrogen called abiraterone inhibits the activity of an enzyme involved in testosterone synthesis in the testes and adrenal glands. In clinical trials, abiraterone has shown promise in treating patients with aggressive end-stage prostate cancer, which is usually refractory to hormone therapy, has metastasized (spread), and is often fatal. Treatment with abiraterone is associated with reductions in tumour size and PSA levels. Its side effects appear to be limited primarily to hypertension, edema, and potassium deficiency. Other drugs that have been investigated for the treatment of men with metastatic hormone-refractory prostate cancer include docetaxel, which inhibits the growth of cancer cells, and sipuleucel-T, which is a vaccine and thus is designed to activate the immune system to attack cancer cells. When used in combination with an immunosuppressant drug called prednisone, docetaxel can prolong patient survival. Clinical trials have indicated that sipuleucel-T also can prolong survival in some patients.



Physicians disagree on the usefulness of routine screening for prostate cancer. Most medical societies and government agencies feel that screening has not proved to reduce prostate cancer mortality and therefore do not recommend screening. Some medical societies, however, recommend an annual PSA test and digital rectal examination at age 50 for most men and at age 45 for men at higher risk. In addition to measuring PSA levels in the diagnosis of prostate cancer, these values can be used to determine a man’s risk of developing the disease. Furthermore, depending on PSA level, a man’s risk of prostate cancer may be lowered by a drug called dutasteride. This agent, originally approved for the treatment of benign prostate hyperplasia, works by inhibiting an enzyme called 5-alpha-reductase, which converts testosterone into dihydrotestosterone. The drug has been shown to be effective in reducing the number of men with high-risk PSA levels who are diagnosed with prostate cancer.