Randomized trials of PSA screening

Abstract

Background: The role of prostate-specific antigen (PSA) testing in prostate cancer (PCa) screening has evolved over recent decades with multiple randomized controlled trials (RCTs) spurring guideline changes. At present, controversy exists due to the indolent nature of many prostate cancers and associated risks of overdiagnosis and overtreatment. This review examines major RCTs evaluating PSA screening to inform clinical practices.

Methods and materials: We summarize findings from primary RCTs investigating PSA screening's impact on PCa mortality and incidence: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, the European Randomized Study of Screening for Prostate Cancer (ERSPC), and the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP).

Results: The PLCO Trial randomized men to annual PSA and DRE screening or usual care, reporting no significant difference in PCa mortality between groups at 17 years (RR 0.93, [95% CI: 0.81-1.08]), yet significantly increased detection and concomitant decreased detection in Gleason 6 (RR 1.17, [95% CI: 1.11-1.23]) and 8-10 disease (RR 0.89, [95% CI: 0.80-0.99]) in the screening group, respectively. The ESPRC Trial randomized men across seven European countries to PSA screening every 2-4 years or usual care, noting a 20% reduction in PCa mortality at 9 years (RR 0.81, [95% CI: 0.65-0.98]) and significant decrease in metastatic disease at 12 years (RR 0.70, [95% CI: 0.60-0.82]). The CAP Trial assessed a single PSA screening test's impact on PCa mortality yielding no significant difference in PCa mortality at 10 years (RR 0.96, [95% CI: 0.85-1.08]). Limitations amongst studies included high contamination between study arms and low compliance with study protocols.

Conclusions: While the CAP and initial PLCO trials showed no significant reduction in PCa mortality, the ERSPC demonstrated a 21% reduction at 13 years, with further benefits at extended follow-up. Differences in outcomes are attributed to variations in trial design, contamination, adherence rates, and PSA thresholds. Future studies are needed focus on optimizing screening intervals, targeting high-risk populations, and incorporating non-invasive diagnostic tools to improve screening efficacy and reduce associated harms.

Keywords: CAP; ERSPC; PLCO; PSA screening; Randomized control trials.