Prostate Cancer Screening Studies Don't Settle Question of Clinical Utility

In 2008, there were about 186,000 new cases of prostate cancer in the United States and of those about 29,000 resulted in death, according to the American Cancer Society. Screening for prostate cancer has become widespread; it usually involves measurement of a blood marker of prostate disease, prostate specific antigen (PSA), and may also include examination of the prostate during a rectal examination. There has been a marked increase in detection of early prostate cancers using screening. Concern has been raised, however, because studies have shown that many prostate cancers are slow-growing and never cause any problems for the man affected by them. Treatment of such a slow-growing cancer could cause unnecessary complications and expense. For this reason, two trials were designed to determine whether screening for prostate cancer can reduce deaths from cancer.

The first trial, a multi-center American study of 77,000 men ages 55 to 74, found that the rate of death from prostate cancer was very low and did not differ significantly between groups receiving annual screening and usual care. The American Prostate, Lung, Colorectal, and Ovarian Cancer trial randomized men to annual PSA testing for six years plus annual digital rectal examination (DRE) for four years, or to no screening. After 10 years, the researchers found 92 prostate cancer deaths in the screening group and 82 in the control group, a nonsignificant difference.

In the second study of 182,000 men ages 50 to 74, from seven European countries, PSA-based screening reduced the rate of death from prostate cancer by 20%, which was just slightly more than a chance difference between the two groups, but was associated with a high risk of overdiagnosis. During an average follow-up of 9 years, there were seven fewer prostate cancer deaths per 10,000 screened men, compared with controls. Researchers noted that to prevent one prostate cancer death, 1410 men had to be screened and 48 additional cases of prostate cancer had to be diagnosed and treated.

Both studies had important limitations that render results ambiguous. For example, in the U.S. study, screening was actually completed in about 85% of those assigned screening and about 50% of control subjects, complicating the process of drawing conclusions from the data. In the European trial, the process of pooling results for participants was problematic because the seven countries’ PSA screening policies varied considerably in screening intervals, PSA cutoffs warranting further evaluation, and inclusion of DRE in initial screening. In addition, both studies are continuing to follow the patients; since prostate cancer is slow-growing, clear evidence on whether there is or isn’t a benefit of screening may not be apparent until the end of the studies.

“Serial PSA screening has at best a modest effect on prostate-cancer mortality during the first decade of follow-up. This benefit comes at the cost of substantial overdiagnosis and overtreatment,” writes Michael J. Barry, MD of Massachusetts General Hospital and Harvard Medical School in an accompanying editorial. He states that the studies do little to quell the longstanding controversy over prostate cancer screening’s usefulness and bolster advice from most current guidelines: Men should discuss prostate cancer screening with their doctor regarding the benefits and risks of screening based on their current health status.

Sources

Andriole GL et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009 Mar 26; 360:1310. Available online at http://dx.doi.org/10.1056/NEJMoa0810696. Accessed March 23, 2009.

Schröder FH et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009 Mar 26; 360:1320. Available online at http://dx.doi.org/10.1056/NEJMoa0810084. Accessed March 23, 2009.

Barry MJ. Screening for prostate cancer — The controversy that refuses to die. N Engl J Med 2009 Mar 26; 360:1351. Available online at http://dx.doi.org/10.1056/NEJMe0901166. Accessed March 23, 2009.

Brett, A. PSA Screening: Initial Reports from Two Randomized Trials. Journal Watch Summary. Available online at http://general-medicine.jwatch.org/cgi/content/full/2009/318/1 through http://general-medicine.jwatch.org. Accessed March 23, 2009.

American Cancer Society. Cancer Facts and Figures, 2008. PDF available for download at http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf through http://www.cancer.org. Accessed April 9, 2009.