Urinary Creatine Riboside Complements PSA to Improve Disease Detection in the Diagnostic Gray Zone of Prostate Cancer

The study investigated whether urinary creatine riboside (CR), a tumor-derived metabolite excreted through the prostatic urethra, can improve prostate cancer diagnosis in the PSA gray zone (3.0-9.99 ng/mL), where approximately 75% of biopsies show no clinically significant cancer. In the NCI-Maryland study with 951 cases and 962 controls (47.6% African American men, median follow-up 11.5 years), urinary CR was measured by UPLC-MS/MS. In the diagnostic gray zone, urinary CR showed markedly superior discrimination compared to PSA alone (AUC 0.93 versus 0.77), and when combined with PSA, the discriminatory ability improved further by 0.17. Urinary CR independently predicted prostate cancer-specific mortality, with the strongest effect in African American men. The researchers concluded that urinary creatine riboside is a candidate non-invasive biomarker that complements PSA for patient triage in the gray zone and predicts prostate cancer-specific mortality.