Effect of Prostate Cancer Screening with Prostate-specific Antigen Testing on Long-term Prostate Cancer-specific...

Earlier evidence syntheses reached uncertain conclusions about the effect of prostate-specific antigen (PSA)-based screening on prostate cancer (PCa)-specific mortality (PCSM). Extended follow-up from major trials has provided an opportunity to re-evaluate the evidence.

To estimate the effect of PSA-based screening versus no screening or usual care on PCSM in individuals engaging in screening.

We systematically searched PubMed, MEDLINE, EMBASE, and CENTRAL through October 2025 for randomized controlled trials (RCTs) comparing PSA-based screening with no screening or usual care among adults with prostates. The primary outcome was PCSM at the longest available follow-up. Secondary outcomes were PCSM beyond 12 yr and PCSM closest to 10 yr of follow-up. Risk of bias was assessed using the Risk Of Bias instrument for Use in SysTematic reviews-for RCTs (ROBUST-RCT). Incidence rate ratios were pooled using fixed-effect models. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

We included 5 RCTs analyzing 721,607 participants aged 45-80 yr of age with 11-23 yr of follow-up. PSA-based screening, with a high certainty in the evidence, demonstrated a reduced risk of PCSM at the longest follow-up (p < 0.001). Secondary analyses suggested greater relative PCSM reduction with longer follow-up. The overall effect was observed despite limitations including differing screening protocols and control-arm contamination, which likely underestimated benefit.

With 11-23 yr of follow-up, high-certainty evidence demonstrates that PSA-based PCa screening is associated with reduced PCSM among individuals who engage in screening-a finding that contrasts with earlier evidence syntheses. This finding does not in itself justify population-based screening or imply that every well-informed individual would elect to undergo screening. This PCSM benefit should be weighed against known harms and consider emerging approaches under study that may mitigate these harms.