Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review)

Prostate-specific antigen (PSA) screening reduces prostate cancer (PCa) mortality but is limited by overdiagnosis and poor specificity for clinically significant disease.These limitations drive the need for more accurate biomarkers to distinguish aggressive cancers from indolent lesions.The present review examined advanced blood-based markers, including PSA isoforms, liquid biopsy components and the Prostate Health Index; urinary biomarkers, such as PCa antigen 3, transmembrane protease serine 2-v-ets erythroblastosis virus E26 oncogene homolog fusion and the MyProstateScore 2.0 panel; and genetic markers ranging from high-penetrance germline mutations to polygenic risk scores.It further explored the integration of these biomarkers with multiparametric MRI, risk-calculator models and health-economic evaluations to optimize screening pathways.Future directions involve multi-omic profiling, artificial intelligence and novel biosensing technologies.The present review aimed to provide a comprehensive and balanced perspective on emerging biomarkers that are reshaping personalized PCa screening. Contents1. Introduction 2. Blood-based biomarkers: Refining the serum signature 3. Urinary biomarkers: A non-invasive window to the prostate 4. Genetic and polygenic risk markers: Informing inherited susceptibility 5. Integrative strategies and clinical decision-making 6. Future directions 7. Conclusions