Prostate-specific antigen-based screening for prostate cancer: A systematic review to inform an American Cancer Society guideline.

Abstract

The purpose of this systematic review was to identify and synthesize the evidence on the benefits and harms of prostate-specific antigen (PSA)-based screening for prostate cancer to inform the American Cancer Society's updated guideline. PubMed and the Cochrane Central Register of Controlled Trials were searched for published and gray literature through December 4, 2023, and updated through October 29, 2025, which allowed for approximately 3 months of overlap with searches conducted for the previous guideline. Eligible studies included randomized and nonrandomized comparisons of PSA-based screening strategies to no screening or other screening strategies. Low- and medium-risk of bias systematic reviews were included, and their findings were supplemented with studies published after the systematic review. One investigator abstracted study data, and a second confirmed. Two investigators independently assessed the risk of bias and strength of evidence, and discrepancies were resolved by consensus. Twenty-nine publications were included: two publications from a 2018 systematic review of PLCO, CAP, and ERSPC; 23 subsequent publications from six trials (PLCO, CAP, ERSPC, Göteborg-1, Rotterdam Pilot 1, and ProScreen); and four observational studies. PSA-based screening was associated with increased detection of low-risk prostate cancer, reduced incidence of advanced or metastatic disease at diagnosis, and reduced cumulative incidence of metastatic disease. Screening was associated with a reduction in prostate cancer-specific mortality in some trials, although findings were inconsistent and likely depended on screening protocols, PSA thresholds, participant characteristics, and other factors. Harms of screening included overdiagnosis, false-positive test results, biopsy-related complications, and downstream treatment harms.