PRACTICE CHANGER
Do not routinely screen all men over the age of 50 for prostate cancer with the prostate-specific antigen (PSA) test. Consider screening men younger than 75 with no cardiovascular or cancer risk factors—the only patient population for whom PSA testing appears to provide even a small benefit.1,2
STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis of 6 randomized controlled trials (RCTs) with methodological limitations, and a post hoc analysis of a large RCT.
Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomized controlled trials. BMJ. 2010;341:c4543.
Crawford ED, Grubb R 3rd, Black A, et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol. 2011;29:355-361.
ILLUSTRATIVE CASES
A 65-year-old obese man with high blood pressure comes in for a complete physical and asks if he should have the “blood test for cancer.” He had a normal prostate specific antigen (PSA) the last time he was tested, but that was 10 years ago. What should you tell him?
A 55-year-old man schedules a routine check-up and requests a PSA test. His last test, at age 50, was normal. The patient has no known medical problems and no family history of prostate cancer, and he exercises regularly and doesn’t smoke. How should you respond to his request for a PSA test?
Prostate cancer is the second leading cause of cancer deaths among men in the United States, after lung cancer. One in 6 American men will be diagnosed with prostate cancer; for about 3% of them, the cancer will be fatal.3,4
Widespread testing without evidence of efficacy
The PSA test was approved by the US Food and Drug Administration (FDA) in 1986.5 Its potential to detect early prostate cancer in the hope of decreasing morbidity and mortality led to widespread PSA screening in the 1990s, before data on the efficacy of routine screening existed.
By 2002, only one low-quality RCT that compared screening with no screening had been published. The investigators concluded that screening resulted in lower mortality rates, but a subsequent (and superior) intention-to-treat analysis showed no mortality benefit.6 Two large RCTs, both published in 2009, reported conflicting results.7,8
The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 182,000 men ages 50 to 74 years and randomized them to either PSA screening every 4 years or no screening. Prostate cancer-specific mortality was 20% lower for those in the screening group compared with the no-screening group; however, the absolute risk reduction was only 0.71 deaths per 1000 men.7
The US Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) Screening Trial randomized 77,000 men ages 55 to 74 years to either annual PSA and digital rectal examination (DRE) screening or usual care. After 7 years of follow-up, no significant difference was found in prostate cancer deaths or all-cause mortality in the screening group vs the control group. It is important to note, however, that 52% of the men in the control group had ≥1 PSA screening during the study period, which decreased the researchers’ ability to fully assess the benefits of screening.8
PSA’s limitations and potential harmful effects
The PSA test’s significant limitations and potentially harmful effects counter the potential benefits of screening. About 75% of positive tests are false positives, which are associated with psychological harm in some men for up to a year after the test.6 In addition, diagnostic testing and treatment for what may be nonlife-threatening prostate cancer can cause harm, including erectile dysfunction (ED), urinary incontinence, bowel dysfunction, and death. Rates of ED and incontinence 18 months after radical prostatectomy are an estimated 59.9% and 8.4%, respectively.9
Do the benefits of PSA testing outweigh the harms—and for which men? The meta-analysis and post hoc analysis detailed in this PURL help clear up the controversy.
STUDY SUMMARY: Widespread screening doesn’t save lives
Djulbegovic et al examined 6 RCTs, including the ERSPC and PLCO studies described earlier, that compared screening for prostate cancer (PSA with or without DRE) with no screening or usual care.1 Together, the studies included nearly 390,000 men ages 45 to 80 years, and had 4 to 15 years of follow-up. The results showed that routine screening for prostate cancer had no statistically significant effect on all-cause mortality (relative risk [RR]=0.99; 95% confidence interval [CI], 0.97-1.01), death from prostate cancer (RR=0.88; 95% CI, 0.71-1.09), or diagnosis of stage III or IV prostate cancer (RR=0.94; 95% CI, 0.85-1.04). Routine screening did, however, increase the probability of being diagnosed with prostate cancer at any stage, especially at stage I. For every 1000 men screened, on average, 20 more cases of prostate cancer were diagnosed.