title: Patient-specific Meta-analysis of 2 Clinical Validation Studies to Predict Pathologic Outcomes in Prostate Cancer Using the 17-Gene Genomic Prostate Score.
abstract: OBJECTIVE
  To perform patient-specific meta-analysis (MA) of two independent clinical validation studies of a 17-gene biopsy-based genomic assay as a predictor of favorable pathology at radical prostatectomy.
  
  
  METHODS
  Patient-specific MA was performed on data from 2 studies (732 patients) using the Genomic Prostate Score (GPS; scale 0-100) together with Cancer of the Prostate Risk Assessment (CAPRA) score or National Comprehensive Cancer Network (NCCN) risk group as predictors of the likelihood of favorable pathology (LFP). Risk profile curves associating GPS with LFP by CAPRA score and NCCN risk group were generated. Decision curves and receiver operating characteristic curves were calculated using patient-specific MA risk estimates.
  
  
  RESULTS
  Patient-specific MA-generated risk profiles ensure more precise estimates of LFP with narrower confidence intervals than either study alone. GPS added significant predictive value to each clinical classifier. A model utilizing GPS and CAPRA provided the most risk discrimination. In decision-curve analysis, greater net benefit was shown when combining GPS with each clinical classifier compared with the classifier alone. The area under the receiver operating characteristic curve improved from 0.68 to 0.73 by adding GPS to CAPRA, and 0.64 to 0.70 by adding GPS to NCCN risk group. The proportion of patients with LFP >80% increased from 11% using NCCN risk group alone to 23% using GPS with NCCN. Using GPS with CAPRA identified the highest proportion-31%-of patients with LFP >80%.
  
  
  CONCLUSIONS
  Patient-specific MA provides more precise risk estimates that reflect the complete body of evidence. GPS adds predictive value to 3 widely used clinical classifiers, and identifies a larger proportion of low-risk patients than identified by clinical risk group alone.
authors.affiliation: Madigan Army Medical Center, Tacoma, WA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Brand
authors.affiliation: Genomic Health, Inc., Redwood City, CA. Electronic address: nzhang@genomichealth.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Genomic Health, Inc., Redwood City, CA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Crager
authors.affiliation: Genomic Health, Inc., Redwood City, CA.
authors.forename: Tara
authors.initials: T
authors.lastname: Maddala
authors.affiliation: Genomic Health, Inc., Redwood City, CA.
authors.forename: Anne
authors.initials: A
authors.lastname: Dee
authors.affiliation: Joint Pathology Center, Silver Spring, MD.
authors.forename: Isabell A
authors.initials: IA
authors.lastname: Sesterhenn
authors.affiliation: University of California, San Francisco, San Francisco, CA.
authors.forename: Jeffry P
authors.initials: JP
authors.lastname: Simko
authors.affiliation: University of California, San Francisco, San Francisco, CA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cooperberg
authors.affiliation: Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD.
authors.forename: Shiv
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, MD.
authors.forename: Inger L
authors.initials: IL
authors.lastname: Rosner
authors.affiliation: University of California, San Francisco, San Francisco, CA.
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
authors.affiliation: Genomic Health, Inc., Redwood City, CA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Febbo
authors.affiliation: University of California, San Francisco, San Francisco, CA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.affiliation: Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cullen
authors.affiliation: Genomic Health, Inc., Redwood City, CA.
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Lawrence
mesh_terms: D000328:Adult; D000368:Aged; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D054928:Validation Studies as Topic