Prostate cancer information centre:
Prostate cancer is a form of cancer that develops in the prostate, a gland in the malereproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize (spread) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction. Other symptoms can potentially develop during later stages of the disease.
Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States.Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men, many never have symptoms, undergo no therapy, and eventually die of other causes. This is because cancer of the prostate is, in most cases, slow-growing, symptom-free, and since men with the condition are older they often die of causes unrelated to the prostate cancer, such as heart/circulatory disease, pneumonia, other unconnected cancers, or old age. About 2/3 of cases are slow growing, the other third more aggressive and fast developing.
Many factors, including genetics and diet, have been implicated in the development of prostate cancer. The presence of prostate cancer may be indicated by symptoms, physical examination,prostate specific antigen (PSA), or biopsy. The PSA test increases cancer detection but does not decrease mortality.Suspected prostate cancer is typically confirmed by taking a biopsy of the prostate and examining it under a microscope. Further tests, such as CT scans and bone scans, may be performed to determine whether prostate cancer has spread.
Treatment options for prostate cancer with intent to cure are primarily surgery, radiation therapy, and proton therapy. Other treatments, such as hormonal therapy, chemotherapy, cryosurgery, and high intensity focused ultrasound (HIFU) also exist, depending on the clinical scenario and desired outcome.
The age and underlying health of the man, the extent of metastasis, appearance under the microscope, and response of the cancer to initial treatment are important in determining the outcome of the disease. The decision whether or not to treat localized prostate cancer (a tumor that is contained within the prostate) with curative intent is a patient trade-off between the expected beneficial and harmful effects in terms of patient survival and quality of life.
The prostate is a part of the male reproductive organ that helps make and store seminal fluid. In adult men, a typical prostate is about three centimeters long and weighs about twenty grams. It is located in the pelvis, under the urinary bladder and in front of the rectum. The prostate surrounds part of the urethra, the tube that carries urine from the bladder during urination and semen duringejaculation. Because of its location, prostate diseases often affect urination, ejaculation, and rarely defecation. The prostate contains many small glands which make about twenty percent of the fluid constituting semen. In prostate cancer, the cells of these prostate glands mutate into cancer cells. The prostate glands require male hormones, known as androgens, to work properly. Androgens include testosterone, which is made in the testes; dehydroepiandrosterone, made in the adrenal glands; and dihydrotestosterone, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass.
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.
The most important distinction made by any staging system is whether or not the cancer is still confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have spread elsewhere. Several tests can be used to look for evidence of spread. These include computed tomography to evaluate spread within the pelvis, bone scans to look for spread to the bones, and endorectal coil magnetic resonance imaging to closely evaluate the prostatic capsule and the seminal vesicles. Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis—opposite to what is found in many other cancers that metastasize.
Computed tomography (CT) and magnetic resonance imaging (MRI) currently do not add any significant information in the assessment of possible lymph node metastases in patients with prostate cancer according to a meta-analysis.The sensitivity of CT was 42% andspecificity of CT was 82%. The sensitivity of MRI was 39% and the specificity of MRI was 82%. For patients at similar risk to those in this study (17% had positive pelvic lymph nodes in the CT studies and 30% had positive pelvic lymph nodes in the MRI studies), this leads to apositive predictive value (PPV) of 32.3% with CT, 48.1% with MRI, and negative predictive value (NPV) of 87.3% with CT, 75.8% with MRI.
After a prostate biopsy, a pathologist looks at the samples under a microscope. If cancer is present, the pathologist reports the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The Gleason system is used to grade prostate tumors from 2 to 10, where a Gleason score of 10 indicates the most abnormalities. The pathologist assigns a number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second-most-common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method sometimes used.
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, increased urination at night, difficulty starting and maintaining a steady stream of urine, blood in the urine, andpainful urination. Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland, therefore, directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate gland itself are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.
Advanced prostate cancer can spread to other parts of the body, possibly causing additional symptoms. The most common symptom isbone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the proximal part of the bone. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.
The specific causes of prostate cancer remain unknown. The primary risk factors are age and family history. Prostate cancer is very uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70.However, many men never know they have prostate cancer. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes have found prostate cancer in thirty percent of men in their 50s, and in eighty percent of men in their 70s.Men who have first-degree family members with prostate cancer appear to have double the risk of getting the disease compared to men without prostate cancer in the family.This risk appears to be greater for men with an affected brother than for men with an affected father. In the United States in 2005, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer.Men with high blood pressure are more likely to develop prostate cancer. A 2010 study found that prostate basal cells were the most common site of origin for prostate cancers.
Genetic background may contribute to prostate cancer risk, as suggested by associations with race, family, and specific gene variants. Men with one first-degree relative with prostate cancer have a twofold higher risk, and those with two first-degree relatives have a fivefold greater risk of developing prostate cancer compared with men with no family history. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men.In contrast, the incidence and mortality rates for Hispanic men are one third lower than for non-Hispanic whites. Men who have a brother or father with prostate cancer have twice the risk of developing prostate cancer.Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained byinherited factors.
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.Other linked genes include theHereditary Prostate cancer gene 1 (HPC1), the androgen receptor, and the vitamin D receptor.TMPRSS2-ETS gene family fusion, specifically TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes cancer cell growth.
Loss of cancer suppressor genes,early in the prostatic carcinogenesis, have been localized to chromosomes 8p, 10q, 13q,and 16q. P53mutations in the primary prostate cancer are relatively low and are more frequently seen in Metastatic settings,hence, p53 mutations are late event in pathology of prostate cancer. Other tumor suppressor genes that are thought to play a role in prostate cancer include PTEN (gene)and KAI1. "Up to 70 percent of men with prostate cancer have lost one copy of the PTEN gene at the time of diagnosis" Relative frequency of loss of E-cadherin and CD44 has also been observed.
Evidence from epidemiological studies supports a possible protective role in reducing prostate cancer for dietary Vitamin B6, selenium,vitamin E, lycopene, and soy foods. A study in 2007 cast doubt on the effectiveness of lycopene (found in tomatoes) in reducing the risk of prostate cancer. Lower blood levels of vitamin D may increase the risk of developing prostate cancer. This may be linked to lower exposure to ultraviolet (UV) light, since UV light exposure can increase vitamin D in the body.
Studies comparing men who live in areas of the country with high levels of selenium to men in areas with low levels suggest that this mineral protects against prostate cancer. Selenium is believed to reduce the risk of developing prostate cancer because it keeps cells from proliferating or dying off in a rapid or unusual way. An analysis in 2002 of the Nutritional Prevention of Cancer Trial revealed that the men who took selenium supplements daily were half as likely to be diagnosed with prostate cancer. These findings have been confirmed in most observational studies. However, in 2008, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicated that neither selenium nor vitamin E, alone or in combination, was effective for the primary prevention of prostate cancer. Whether or not selenium helps prevent prostate cancer, researchers at the Dana-Farber Cancer Institute in Boston found that higher selenium levels in the blood may worsen prostate cancer in many men who already have the disease.
Green tea may be protective (due to its catechins content), although the most comprehensive clinical study indicates that it has no protective effect.Other holistic methods are also studied.
Research published in the Journal of the National Cancer Institute suggests that taking multivitamins more than seven times a week can increase the risks of contracting the disease. This research was unable to highlight the exact vitamins responsible for this increase (almost double), although they suggest that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised that those taking multivitamins never exceed the stated daily dose on the label.
A 2007 study published in the Journal of the National Cancer Institute found that men eating cauliflower, broccoli, or one of the othercruciferous vegetables, more than once a week were 40% less likely to develop prostate cancer than men who rarely ate those vegetables.The phytochemicals indole-3-carbinol and diindolylmethane, found in cruciferous vegetables, has antiandrogenic and immune modulating properties.
Many doctors prescribe supplements to prostate cancer patients but currently the efficacy of nutrient supplements is still unknown.Supplements may not be as beneficial to prostate health as micronutrients obatined naturally from the diet.
Folic acid supplements have recently been linked to an increase in risk of developing prostate cancer. A ten-year research study led byUniversity of Southern California researchers showed that men who took daily folic acid supplements of 1 mg were three times more likely to be diagnosed with prostate cancer than men who took a placebo. Folate plays a complex role in prostate cancer and folic acidsupplements have a different effect on prostate cancer than folate naturally found in foods. The supplement form, folic acid, is morebioavailable in the body compared with dietary sources of folate. Folate hydrolase activity is associated with prostate-specific antigen. A small Swedish study of 254 subjects, with a median age of 64, and a follow up of 5 years suggested that folate status is not protective against prostate cancer, however, and like folic acid may even result in a 3 fold increase in early prostate cancer development and risk.Supplements and multivitamins, alcohol and drug consumption, GI disorders, and folate bioavailability were not analyzed in this study.
High alcohol intake may increase the risk of prostate cancer and interfere with folate metabolism. Low folate intake and high alcohol intake may increase the risk of prostate cancer to a greater extent than the sole effect of either one by itself. 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. Folate's effect however was only significant when coupled with low alcohol intake. 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.There was no association found in this study between folic acid supplements and risk of prostate cancer.
The prostate gland has a high concentration of zinc so zinc may play a role in prostate cancer. Researchers studied the relationship between zinc supplement intake of 100 mg/day and the risk of prostate cancer in 46 974 US men over a 14 year period and reported in 2003 that long term zinc supplement of over 100 mg/day intake seemed to be associated with approximately double the risk of developing prostate cancer.
There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Use of thecholesterol-lowering drugs known as the statins may also decrease prostate cancer risk.
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. Finally, obesity and elevated blood levels of testosterone 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.
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.
In 2006, researchers associated a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, with human prostate tumors.Subsequent reports on the virus have been contradictory. A group of US researchers found XMRV protein expression in human prostate tumors,while German scientists failed to find XMRV-specific antibodies or XMRV-specific nucleic acid sequences in prostate cancer samples.