Optimizing Prostate Biopsy Pathways: Integrating MRI–Targeted, Systematic Sampling, and Clinical Judgment in the PSA-Era

Prostate cancer diagnostics have evolved substantially with the integration of multiparametric magnetic resonance imaging (mpMRI), refined prostate-specific antigen (PSA) metrics, and targeted biopsy techniques. While mpMRI has become a central gatekeeper in biopsy decision-making, it is not infallible. Clinically significant prostate cancer may therefore remain undetected, particularly in patients with elevated PSA density, adverse PSA kinetics, or MRI-occult disease. This narrative review synthesizes contemporary evidence on PSA interpretation, mpMRI performance, and biopsy strategy selection, highlighting the limitations of single-parameter approaches. We discuss the diagnostic yield and clinical implications of targeted, systematic, and combined biopsy techniques, emphasizing scenarios in which systematic sampling remains necessary despite negative or equivocal imaging findings. Emerging data support combined targeted and systematic biopsy as the most robust strategy for maximizing the detection of clinically significant disease while limiting overdiagnosis in most biopsy-naive and high-risk patients. By integrating PSA dynamics, prostate volume, imaging findings, and individual risk profiles, a structured, risk-adapted diagnostic pathway can be achieved. The proposed framework is intended as a conceptual, expert-derived clinical aid to support risk-adapted decision-making. It should be interpreted alongside established guidelines, and prospective validation in future studies is warranted.