Michele Brancaccio

Prostate cancer (PCa) screening has long relied on PSA testing, a strategy that has shaped diagnostic pathways for decades but remains limited by substantial overdiagnosis and downstream overtreatment. As screening practices evolve, the relevance of historical evidence must be reconsidered in the context of contemporary diagnostic workflows that now incorporate imaging, refined biopsy techniques, and risk-adapted management. This narrative review examines the transition from PSA-only screening toward modern, risk-adapted early detection strategies. We synthesize evidence supporting the integration of mpMRI, refined biopsy techniques, and active surveillance (AS) as key components of contemporary screening pathways aimed at improving the detection of clinically significant disease while minimizing unnecessary interventions. Particular emphasis is placed on second-line MRI-based approaches, which consistently reduce the number of avoidable biopsies and enhance the diagnostic precision. In addition, we review the role of blood-based and genomic biomarkers in pre-biopsy risk stratification, discussing established tools within a unified framework of individualized screening. The review also contextualizes very recent regulatory developments, including the FDA approval of a novel structure-based PSA assay, as part of the ongoing evolution of biomarker-supported screening rather than a paradigm shift. Overall, this article provides a timely synthesis of mature randomized evidence and emerging diagnostic innovations, offering a clinically grounded perspective on how PCa screening is being reshaped toward more personalized and harm-aware strategies.