Prostate Cancer Screening: Current Controversies and Future Directions

Prostate-specific antigen (PSA) testing has been central to prostate cancer detection since FDA approval for early detection in 1994, yet its widespread application has generated enduring controversy owing to limited specificity, overdiagnosis, and the quality-of-life harms of overtreatment. Prostate cancer is among the most prevalent malignancies in men globally. Major randomized trials, including the European Randomized Study of Screening for Prostate Cancer (ERSPC), the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, and the more recent ProtecT trial, reported divergent conclusions about prostate cancer-specific mortality benefit. International guidelines from the American Urological Association/Society of Urologic Oncology (AUA/SUO), the United States Preventive Services Task Force (USPSTF), and the European Association of Urology (EAU) differ substantially in their recommended age thresholds, screening intervals, and approaches to shared decision-making, reflecting the genuine uncertainty in the evidence base. Emerging modalities, such as multiparametric magnetic resonance imaging, serum biomarkers including the Prostate Health Index and 4Kscore, and germline genomic risk stratification, offer pathways toward more individualized screening. Polygenic risk scores and artificial intelligence-based tools show promise for integrating multiple risk factors, though most approaches remain under active investigation and require prospective validation before routine clinical deployment. This narrative review synthesizes current evidence on PSA-based screening, evaluates the principal sources of controversy, compares international guideline recommendations, and examines emerging risk-stratified approaches. Current evidence supports individualized, risk-adapted screening over universal PSA threshold application, with shared decision-making as the essential framework for integrating emerging biomarker and genomic data into clinical practice.