Blood- and urine-based biomarkers for the detection of clinically significant prostate cancer: a contemporary review

PURPOSE OF REVIEW: Prostate cancer (PCa) is the most common malignancy in men. While prostate-specific antigen (PSA) screening aids early detection, its low specificity leads to unnecessary biopsies and overdiagnosis of low-grade cancers. Blood- and urine-based biomarkers are proposed by clinical guidelines to better identify patients with elevated PSA that can safely avoid more intensive testing (e.g. imaging, biopsy). The current article aims to provide clinicians and researchers with a contemporary assessment of prostate cancer biomarker tests. RECENT FINDINGS: This review focused on prebiopsy blood- and urine-based biomarker tests that are commercially-available and included in clinical guidelines. A systematic search identified 955 studies, of which 14 were published in the past 18 months (July 2023-January 2025) and reported performance metrics for clinically significant PCa (csPCa, defined as grade group ≥2). The literature revealed that blood- [Prostate Health Index (PHI), 4Kscore, and IsoPSA] and urine-based tests [SelectMDx, ExoDx IntelliScore (EPI), and MyProstateScore (MPS, MPS2)] maintained high sensitivity for csPCa while significantly reducing unnecessary biopsies performed relative to PSA-based testing. Furthermore, available data suggest that biomarkers can inform the need for biopsy in patients with equivocal (PI-RADS 3) mpMRI. SUMMARY: Commercially-available, noninvasive biomarker tests consistently outperformed PSA and PSA-based risk calculators for detection of csPCa. Clinical use of these tests appears to substantially reduce the proportion of unnecessary biopsies performed, while maintaining detection of the vast majority of significant cancers.