Prostate-specific antigen (PSA) has been the primary biomarker used for the detection and monitoring of prostate cancer for decades. However, its limited specificity and prognostic accuracy have led to the development of novel molecular and imaging biomarkers aimed at improving the clinical characterization of localized disease. This review critically examines recent advances in urinary biomarkers (e.g., PCA3, SelectMDx), tissue-based genomic assays (Oncotype DX Prostate, Prolaris, Decipher), and imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PET-PSMA). We evaluate their diagnostic performance, prognostic value, and clinical utility in risk stratification and individualized treatment decision-making. Methodological and clinical barriers to their routine implementation are also discussed. Current evidence supports the multidisciplinary integration of these biomarkers to overcome the limitations of PSA, improve biopsy decision-making, better distinguish indolent from aggressive tumors, and optimize therapeutic strategies. Finally, future research directions aimed at validating and incorporating emerging biomarkers into clinical practice are outlined, with the goal of improving outcomes in patients with localized prostate cancer.

Prostate-specific antigen (PSA) has been the main biomarker used for the detection and monitoring of prostate cancer for decades. However, its limited specificity and prognostic accuracy have prompted the development of novel molecular and imaging biomarkers to improve the clinical characterization of localized disease. This review critically examines recent advances in urinary biomarkers (e.g., PCA3, SelectMDx), tissue-based genomic assays (Oncotype DX Prostate, Prolaris, Decipher), and imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PET-PSMA). We evaluate their diagnostic performance, prognostic relevance, and clinical utility in risk stratification and individualized treatment decision-making. Methodological and clinical barriers to their routine implementation are also discussed. Current evidence supports a multidisciplinary integration of these biomarkers to address the limitations of PSA, improve biopsy decision-making, better distinguish indolent from aggressive tumors, and optimize therapeutic strategies. Finally, future research directions aimed at validating and incorporating emerging biomarkers into clinical practice are outlined, with the goal of improving outcomes in patients with localized prostate cancer.