title: A urine-based methylation signature for risk stratification within low-risk prostate cancer.
abstract: 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.
authors.affiliation: Ortho Clinical Diagnostics, 1001 US Route 202, Raritan, NJ 08869, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Jatkoe
authors.affiliation: Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: 1] Department of Surgery, Durham VA Medical Center, Durham, NC 27705, USA [2] Department of Surgery (Urology) and Pathology, Duke University Medical Center, DUMC 2626, Durham, NC 27710, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Freedland
authors.affiliation: Ortho Clinical Diagnostics, 1001 US Route 202, Raritan, NJ 08869, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Ortho Clinical Diagnostics, 1001 US Route 202, Raritan, NJ 08869, USA.
authors.forename: A
authors.initials: A
authors.lastname: Le
authors.affiliation: Ortho Clinical Diagnostics, 1001 US Route 202, Raritan, NJ 08869, USA.
authors.forename: J
authors.initials: J
authors.lastname: Baden
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000652:urine; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000652:urine*; D019175:DNA Methylation; D005982:Glutathione Transferase / Q000235:genetics / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D060787:Neoplasm Grading; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000601:surgery / Q000652:urine; D012307:Risk Factors
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase