Comparing diagnostic prostate cancer biomarkers using a framework of clinically meaningful criteria

To synthesize existing biomarker literature and generate a framework for meaningful comparison between five commonly used diagnostic prostate cancer biomarkers-prostate health index (phi), 4KScore, SelectMDx, ExoDx and MyProstate Score (MPS)-to provide evidence of greatest practical value to providers managing men with an elevated prostate-specific antigen (PSA) who are considering prostate biopsy.

Ten biomarker characteristics reflecting validity, usability and utility were designated as most clinically salient in guiding diagnostic prostate cancer biomarker selection. Whereas usability reflects how well a biomarker individualizes risk and optimizes patient concerns, utility reflects a biomarker's clinical usefulness. A systematic review of the biomarker literature from 2010 to 2022 was performed, and the criteria for each biomarker characteristic were first inductively defined and subsequently determined for each respective biomarker.

Nearly all biomarkers possess wide validity, with phi, 4KScore and MPS validated in Black populations. Compared to other biomarkers, 4KScore had the best usability. For urine-based biomarkers, the better usability of ExoDx versus MPS is offset by its worse validity and utility. All serum-based biomarkers have very high discriminative accuracy and were consequently more accurate in detecting high-grade prostate cancer versus urine-based biomarkers. Overall, 4KScore had the best utility.

Our framework enables meaningful comparison of diagnostic prostate cancer biomarkers using criteria most salient to patients and clinicians. We demonstrate that the 4KScore currently possesses the best overall features; despite emerging evidence, more clinical utility, comparative and non-White population validation studies are needed.