title: A genomic classifier predicting metastatic disease progression in men with biochemical recurrence after prostatectomy.
abstract: BACKGROUND
  Due to their varied outcomes, men with biochemical recurrence (BCR) following radical prostatectomy (RP) present a management dilemma. Here, we evaluate Decipher, a genomic classifier (GC), for its ability to predict metastasis following BCR.
  
  
  METHODS
  The study population included 85 clinically high-risk patients who developed BCR after RP. Time-dependent receiver operating characteristic (ROC) curves, weighted Cox proportional hazard models and decision curves were used to compare GC scores to Gleason score (GS), PSA doubling time (PSAdT), time to BCR (ttBCR), the Stephenson nomogram and CAPRA-S for predicting metastatic disease progression. All tests were two-sided with a type I error probability of 5%.
  
  
  RESULTS
  GC scores stratified men with BCR into those who would or would not develop metastasis (8% of patients with low versus 40% with high scores developed metastasis, P<0.001). The area under the curve for predicting metastasis after BCR was 0.82 (95% CI, 0.76-0.86) for GC, compared to GS 0.64 (0.58-0.70), PSAdT 0.69 (0.61-0.77) and ttBCR 0.52 (0.46-0.59). Decision curve analysis showed that GC scores had a higher overall net benefit compared to models based solely on clinicopathologic features. In multivariable modeling with clinicopathologic variables, GC score was the only significant predictor of metastasis (P=0.003).
  
  
  CONCLUSIONS
  When compared to clinicopathologic variables, GC better predicted metastatic progression among this cohort of men with BCR following RP. While confirmatory studies are needed, these results suggest that use of GC may allow for better selection of men requiring earlier initiation of treatment at the time of BCR.
authors.affiliation: Brady Urological Institute, John Hopkins Medical Institute, Baltimore, MD, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Ross
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: F Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Ghadessi
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Erho
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Crisan
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Buerki
authors.affiliation: Brady Urological Institute, John Hopkins Medical Institute, Baltimore, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sundi
authors.affiliation: Department of Pathology, University of Southern California, Los Angeles, CA, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Mitra
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: I A
authors.initials: IA
authors.lastname: Vergara
authors.affiliation: EMMES Canada, Burnaby, BC, Canada.
authors.forename: D J S
authors.initials: DJ
authors.lastname: Thompson
authors.affiliation: 1] GenomeDx Biosciences, Vancouver, BC, Canada [2] Department of Pathology, University of Southern California, Los Angeles, CA, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Triche
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Bergstralh
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Brady Urological Institute, John Hopkins Medical Institute, Baltimore, MD, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Schaeffer
mesh_terms: D000368:Aged; D018450:Disease Progression; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D012372:ROC Curve; D012008:Recurrence; D015203:Reproducibility of Results
chemical_list: D017430:Prostate-Specific Antigen