The current prostate cancer (PCa) screen test, prostate-specific antigen (PSA), has a high sensitivity for PCa but low specificity for high-risk, clinically significant PCa (csPCa), resulting in overdiagnosis and overtreatment of non-csPCa. Early identification of csPCa while avoiding unnecessary biopsies in men with non-csPCa is challenging. We built an optimized machine learning platform (ClarityDX) and showed its utility in generating models predicting csPCa. Integrating the ClarityDX platform with blood-based biomarkers for clinically significant PCa and clinical biomarker data from a 3448-patient cohort, we developed a test to stratify patients' risk of csPCa; called ClarityDX Prostate. When predicting high risk cancer in the validation cohort, ClarityDX Prostate showed 95% sensitivity, 35% specificity, 54% positive predictive value, and 91% negative predictive value, at a ≥ 25% threshold. Using ClarityDX Prostate at this threshold could avoid up to 35% of unnecessary prostate biopsies. ClarityDX Prostate showed higher accuracy for predicting the risk of csPCa than PSA alone and the tested model-based risk calculators. Using this test as a reflex test in men with elevated PSA levels may help patients and their healthcare providers decide if a prostate biopsy is necessary.

Department of Oncology University of Alberta Edmonton T6G 2E1 AB Canada

Department of Surgery McGill University Montreal H3G 2M1 QC Canada

Department of Surgical Oncology University Health Network Toronto ON Canada

Department of Surgical Oncology University of Calgary Prostate Cancer Centre Calgary T2P 1P9 AB Canada

Department of Urology 3rd Faculty of Medicine of Charles University and Thomayer University Hospital Prague Czech Republic

Division of Urology Department of Surgery Mount Sinai Hospital Toronto M5G 1X5 ON Canada

Division of Urology Department of Surgery University of Alberta Kipnes Urology Centre Edmonton T6G 1Z1 AB Canada

Division of Urology Department of Surgery University of Toronto Toronto M5T 1P5 ON Canada

James Buchanan Brady Urological Institute Johns Hopkins University School of Medicine Baltimore 21287 MD USA

Nanostics Inc 4550 10230 Jasper Avenue Edmonton T5J 4P6 AB Canada

UCLA Health Westwood Urology 200 Medical Plaza Suite 140 Los Angeles CA 90095 USA

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