Background: Prostate cancer is the second most common cancer in men worldwide, and the second deadliest cancer among men in the United States. Screening for curative early-stage disease has been supported as a means to decrease mortality, but controversy persists about the benefits and harms. A 2006 systematic review from the Cochrane Library reported insufficient evidence to support or refute the benefits of prostate cancer screening. However, this review was based on two randomized controlled trials that had significant design flaws. Since that time, four additional large studies have been published. Djulbegovic and colleagues performed an updated systematic review and meta-analysis on the effect of prostate cancer screening on overall and disease-specific mortality.
The Study: The authors searched electronic databases, including Medline, Embase, and the Cochrane Registry of Controlled Trials; abstract proceedings; and bibliographies of all eligible studies from January 1, 2005, to July 13, 2010. Studies published before the previous systematic review was completed were eligible. Randomized controlled trials that compared screening versus no screening of asymptomatic men were eligible if they included prostate-specific antigen (PSA) testing with or without digital rectal examination (DRE). Studies that included participants with previously diagnosed prostate cancer were excluded.
The primary outcomes were all-cause and prostate cancer–specific mortality, diagnosis of prostate cancer, effect of screening on stage at diagnosis, false-positive and false-negative results, harms of screening, quality of life, and cost-effectiveness. The quality and limitations of each study were evaluated on multiple criteria; individual outcomes were given a quality of evidence rating of high, moderate, low, or very low. The effects of screening were reported as relative risks for all outcomes studied.
Results: Of 493 relevant references, six randomized clinical trials met inclusion criteria. Of these, five used PSA testing with or without DRE, and the sixth added PSA testing to DRE during the study. The evidence was considered moderate quality for all-cause and disease-specific mortality. Four trials with 256,019 participants provided data for all-cause mortality, and five trials with 302,500 men were used to calculate prostate cancer–specific mortality. No differences in all-cause or disease-specific mortality between the screened and unscreened groups were found. Based on low-quality evidence, screening resulted in a 46 percent relative increase in prostate cancer diagnoses, although subgroup analysis attributed most of this to stage I cancer. Screening did not improve diagnosis of stages II, III, and IV prostate cancer. This study has some notable limitations. Methodologic problems in the studies resulted in the evidence being downgraded from high to moderate quality for mortality, and the relatively short length of follow- up (i.e., four to 14 years) may not have been sufficient to detect differences in mortality. Finally, the evidence was insufficient to assess screening on high-risk groups.
Conclusion: The authors conclude that screening effectively diagnoses more early-stage prostate cancers. The best available evidence suggests that screening does not improve overall or prostate cancer–specific survival.