Prostate Cancer Screening/Prevention
Overview
Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.
The prostate is a male sex gland that is located between the bladder and the rectum. Prostate cancer occurs commonly in older men and is the second leading cause of cancer death in men in the United States. Prostate cancer is typically a disease of aging. It may persist undetected for many years without causing symptoms. In fact, most men die with prostate cancer not from prostate cancer. Approximately 20% of men will develop prostate cancer during their lifetime, yet only 3% will actually die of the disease.
The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (e.g. the correlation between smoking and lung cancer), while other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer.
Heredity or Genetic Factors
Researchers have estimated that approximately 9% of prostate cancers may be the result of heritable susceptibility genes. Approximately 15% of men with prostate cancer have a first-degree male relative (father or brother) with prostate cancer, compared with 8% of the general population. Identification of specific genes involved in hereditary prostate cancer has proved challenging, but research in this area continues. Mutations in the BRCA2 gene—which have been linked with breast and ovarian cancer in women—appear to increase the risk of prostate cancer in men.[1]
Environmental or Non-Genetic Factors
Researchers are unsure why one man will develop prostate cancer and another will not. Interestingly, when people from areas with low prostate cancer rates move to areas with higher prostate cancer rates, they assume the rates of their new environment, although their genetic make-up clearly has not changed. This suggests that environmental factors may play a larger role than genetic factors in the development of prostate cancer. Although the causes of prostate cancer remain ambiguous, researchers have identified several risk factors that are associated with prostate cancer.
Age: The incidence of prostate cancer increases dramatically with increasing age. It is unusual for prostate cancer to occur in men under the age of 50. Prostate cancer is most common in men over the age of 55, with the median age at diagnosis being 68.[2] Over the course of a lifetime, one in six men will be diagnosed with prostate cancer.
Race: Prostate cancer rates are highest among blacks, intermediate among whites, and lowest among Asian/Pacific Islanders and Native Americans. Black men are more than 50% more likely to develop prostate cancer as white men and are twice as likely to die from the disease.
Diet: Studies have generally not found strong links between specific dietary practices and risk of prostate cancer. Although some early studies reported that vitamin E and selenium may reduce the risk of prostate cancer, a more definitive clinical trial failed to find a benefit of either nutrient.[3] Eating a healthy diet can, however, reduce your risk of other cancers and other common health problems such as heart disease and diabetes. A healthy diet is one that is rich in fruits and vegetables and whole grains and that allows you to maintain a healthy body weight. In addition, for the purposes of cancer prevention, the American Cancer Society recommends limiting intake of red meat and alcohol.[4]
Prevention
Many questions remain about the causes and prevention of prostate cancer, and researchers continue to evaluate medications, dietary factors, and behaviors that may reduce risk.
5-alpha-reductase inhibitors: The 5-alpha-reductase enzymes convert testosterone to another hormone known as dihydrotestosterone (DHT). DHT is the most potent male hormone in the prostate. Drugs that inhibit 5-alpha-reductase are used to treat benign prostatic hyperplasia, and may also reduce the risk of prostate cancer in men at high risk of the disease.[5] [6] These drugs include finasteride and dutasteride.
Screening and Early Detection
For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.
Screening for prostate cancer is a complicated and controversial topic. There is still no clear evidence that screening for prostate cancer reduces the risk of death from this disease. Furthermore, all screening tests carry some risks. In the case of screening for prostate cancer, one of the risks is overdiagnosis (the diagnosis of indolent cancers that will not cause problems during the man’s lifetime). Overdiagnosis can lead to unnecessary cancer treatment.
In light of the uncertainties regarding benefit, men are often advised to talk with their doctor about screening for prostate cancer, and then to make an individualized decision about the need for screening. The American Cancer Society, for example, recommends that men who are in relatively good health and who expect to live for at least 10 more years make a decision about prostate cancer screening after talking with their doctor about the uncertainties, risks, and potential benefits of screening. These talks should start at age 50 for men at average risk of prostate cancer and earlier for men at increased risk of prostate cancer (such as African-American men and men with a family history of prostate cancer). [7]
For men who choose to be screened, screening often involves a blood test to measure levels of a protein known as prostate-specific antigen (PSA). Screening may also involve a digital-rectal exam and/or a transrectal ultrasound.
PSA Blood Test: A simple blood test allows laboratory technicians to determine PSA levels. Prostate-specific antigen (PSA) is a protein that is normally secreted and disposed of by the prostate gland. High PSA levels may indicate the presence of prostate cancer cells or other noncancerous prostate conditions.
Digital Rectal Exam (DRE): During a digital rectal exam (DRE), a physician inserts a gloved finger into the rectum to assess the texture and size of the prostate. The DRE is the most common prostate screening procedure and has been used for many years; however, whether the test is effective in decreasing the number of deaths from prostate cancer has yet to be determined.
Transrectal Ultrasonography: During transrectal ultrasonography, a small probe is inserted into the rectum. The probe emits high frequency sound waves that bounce off of the prostate and produce echoes. A computer uses these echoes to create a picture called a sonogram that can show abnormal areas. Researchers have yet to determine whether transrectal ultrasonography is effective in reducing the number of deaths from prostate cancer.
Strategies to Improve Screening and Prevention
The potential for earlier detection and higher cure rates increases with the advent of more refined screening techniques. In an effort to provide more screening options and perhaps more effective prevention strategies, researchers continue to explore new techniques for the screening and early detection of cancer.
Improved PSA testing: Researchers continue to develop and refine laboratory tests to improve the specificity of PSA testing. PSA results that are more specific may help to eliminate the need for further invasive testing, relieve anxiety and reduce medical costs in patients with elevated PSA levels who have benign conditions.
Prostate specific antigens may be found in various forms in the blood, which can create difficulties with the specificity of PSA testing. Prostate specific antigens may be bound to different molecules in the blood or may exist as isolated “free” proteins. Alpha 1-protease inhibitor is one of the specific proteins that is commonly bound to PSA in the blood. Previous studies have shown that the ratio of free PSA to total PSA (all different forms of PSA) improves the accuracy of the detection of prostate cancer. In order to further derive specificity of PSA testing, scientists have recently developed a blood test, which can detect the presence of alpha 1-protease inhibitor bound to PSA.
Insulin-like Growth Factor: Insulin-like growth factor (IGF-I) and intact IGF-binding protein-3 (IGF-BP3) might help distinguish benign prostatic hyperplasia (BPH) from prostate cancer. Increased levels of IGF-I and IGF-BP3 in men with low to moderate PSA levels are predictive of prostate cancer. In one study performed in Canada in 2000, researchers measured IGF-I and IGF-BP3 levels in two groups of men, those with BPH and those with prostate cancer whose PSA levels were moderate. The men with prostate cancer had significantly higher IGF-I and IGF-BP3 levels than the men with BPH. The researchers concluded that the ratio of IGF-I and IGF-BP3 to free PSA was superior to the currently used free/total PSA ratio in discriminating between BPH and prostate cancer.
References
[1] Foulkes WD. Inherited susceptibility to common cancers. New England Journal of Medicine. 2008;359:2143-53.
[2] Horner MJ, Ries LAG, Krapcho M, Neyman N, Aminou R, Howlader N, Altekruse SF, Feuer EJ, Huang L, Mariotto A, Miller BA, Lewis DR, Eisner MP, Stinchcomb DG, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2006/, based on November 2008 SEER data submission, posted to the SEER web site, 2009.
[3] Lippman SM, Klein EA, Goodman PJ et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers. The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009; 301(1):39-51
[4] Doyle C, Kushi LH, Byers T et al. Nutrition and physical activity during and after cancer treatment: an American Cancer Society Guide for informed choices. CA: A Cancer Journal for Clinicians. 2006;56:323-353.
[5] Andriole G, Bostwick DG, Brawley OW et al. Effect of dutasteride on the risk of prostate cancer. New England Journal of Medicine. 2010;362:1192-202.
[6] Thompson IM, Goodman PJ, Tangen CM et al. The influence of finasteride on the development of prostate cancer. New England Journal of Medicine. 2003;349:215-24.
[7] American Cancer Society. Prostate Cancer: Early Detection. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_6x_Prostate_Cancer_Early_Detection.asp?sitearea=&level= Accessed April 1, 2010.
