title: Tissue-based Genomics Augments Post-prostatectomy Risk Stratification in a Natural History Cohort of Intermediate- and High-Risk Men.
abstract: BACKGROUND
  Radical prostatectomy (RP) is a primary treatment option for men with intermediate- and high-risk prostate cancer. Although many are effectively cured with local therapy alone, these men are by definition at higher risk of adverse pathologic features and clinical disease recurrence. It has been shown that the Decipher test predicts metastatic progression in cohorts that received adjuvant and salvage therapy following RP.
  
  
  OBJECTIVE
  To evaluate the Decipher genomic classifier in a natural history cohort of men at risk who received no additional treatment until the time of metastatic progression.
  
  
  METHODS
  Retrospective case-cohort design for 356 men who underwent RP between 1992 and 2010 at intermediate or high risk and received no additional treatment until the time of metastasis. Participants met the following criteria: (1) Cancer of the Prostate Risk Assessment postsurgical (CAPRA-S) score ≥3; (2) pathologic Gleason score ≥7; and (3) post-RP prostate-specific antigen nadir <0.2 ng/ml.
  
  
  METHODS
  The primary endpoint was defined as regional or distant metastases. Time-dependent receiver operating characteristic (ROC) curves, extension of decision curve analysis to survival data, and univariable and multivariable Cox proportional-hazards models were used to measure the discrimination, net benefit, and prognostic potential of genomic and pathologic risk factors. Cumulative incidence curves were constructed using Fine-Gray competing-risks analysis with appropriate weighting of the controls to account for the case-cohort study design.
  
  
  CONCLUSIONS
  Ninety six patients had unavailable tumor blocks or failed microarray quality control. Decipher scores were then obtained for 260 patients, of whom 99 experienced metastasis. Decipher correlated with increased cumulative incidence of biochemical recurrence, metastasis, and prostate cancer-specific mortality (p<0.01). The cumulative incidence of metastasis was 12% and 47% for patients with low and high Decipher scores, respectively, at 10 yr after RP. Decipher was independently prognostic of metastasis in multivariable analysis (hazard ratio 1.26 per 10% increase; p<0.01). Decipher had a c-index of 0.76 and increased the c-index of Eggener and CAPRA-S risk models from 0.76 and 0.77 to 0.86 and 0.87, respectively, at 10 yr after RP. Although the cohort was large, the single-center retrospective design is an important limitation.
  
  
  CONCLUSIONS
  In a patient population that received no adjuvant or salvage therapy after prostatectomy until metastatic progression, higher Decipher scores correlated with clinical events, and inclusion of Decipher scores improved the prognostic performance of validated clinicopathologic risk models. These results confirm the utility already reported for Decipher.
  
  
  RESULTS
  The Decipher test improves identification of patients most at risk of metastatic progression and death from prostate cancer after radical prostatectomy.
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Ross
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Johnson
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Kasra
authors.initials: K
authors.lastname: Yousefi
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: Department of Cancer Biology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Marchionni
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Fedor
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Glavaris
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Voleak
authors.initials: V
authors.lastname: Choeurng
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Buerki
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Erho
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Lucia L
authors.initials: LL
authors.lastname: Lam
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Humphreys
authors.affiliation: Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Faraj
authors.affiliation: Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Stephania M
authors.initials: SM
authors.lastname: Bezerra
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Trock
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD, USA; Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA. Electronic address: eschaeffer@jhmi.edu.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schaeffer
mesh_terms: D016022:Case-Control Studies; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011184:Postoperative Period; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D012313:RNA / Q000032:analysis*; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment
chemical_list: D012313:RNA; D017430:Prostate-Specific Antigen
keywords: Genomic classifier; Metastasis; Prognosis; Prostate cancer; Transcriptome