Biomarker use in the prostate cancer screening pathway: Maps of the evidence

Prostate-specific antigen (PSA)-based screening provides limited information about which individuals may harbor clinically significant prostate cancer (csPCa) and benefit from biopsy; tools such as magnetic resonance imaging (MRI) and biomarkers are being evaluated to improve risk stratification. Clinical utility reflects balancing reducing biopsies with avoiding missed csPCas, and biomarkers have been proposed to inform these decisions. In this study, evidence maps were constructed to characterize the clinical utility of biomarkers in the prostate cancer screening pathway, with or without MRI and other tools. PubMed and the Cochrane Central Register of Controlled Trials were searched from inception to October 2025 for studies evaluating common blood-, urine-, and saliva-based biomarkers in asymptomatic adults after an abnormal PSA. Eligible studies compared biomarker-based pathways with other strategies and reported clinical utility measures. Screening pathways were classified as "biomarker" or "nonbiomarker," and findings were categorized by whether study investigators reported greater clinical utility for one pathway, the other, or no difference. Across 68 studies, biomarker-based pathways were generally reported to reduce biopsies while maintaining csPCa detection compared to nonbiomarker pathways. Results were broadly consistent across biomarkers. Studies generally reported better clinical utility when biomarkers were used concurrently with or after MRI compared to biomarker alone, although few evaluated sequencing. Limited evidence suggests that biomarkers may add value in individuals undergoing repeat biopsy or with equivocal MRI findings, whereas their benefit beyond MRI was less clear in biopsy-naive populations. Biomarkers improve risk stratification after an elevated PSA, and may enhance decision-making when used alongside MRI. However, heterogeneity in study populations and evaluated pathways limits interpretation.