A urine-based methylation signature for risk stratification within low-risk prostate cancer

Background: Prostate cancer overdiagnosis and overtreatment represents a major problem. Many men with low-grade disease on biopsy are undergraded and they harbour high-grade disease at prostatectomy with no reliable way to identify these men. We used a novel urine-based 2-gene methylation test to identify prostate cancers with aggressive features. Methods: Following a proof of concept study in 100 post-radical prostatectomy tissue samples, urine samples were tested from 665 men at multiple U.S. centers undergoing prostate needle biopsy for elevated prostate-specific antigen (2-10 ng ml(-1)). A prediction model was then developed from a combination of clinical factors and the urine-based markers. It was then prospectively tested for accurate prediction of adverse disease (surgical Gleason score >= 7 and/or a pathological stage >= T3a) using urine from a separate cohort of 96 men before radical prostatectomy. Results: Among pre-prostatectomy men with a biopsy Gleason score <7, 41% had adverse disease of which 100% were correctly identified by the test with a negative predictive value of 100% (95% confidence interval, 86-100%). Conclusions: This urine-based test accurately identifies men with clinical low-risk disease who do not have adverse pathology in their prostates and would be excellent candidates for active surveillance.