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. 2018 Feb;73(2):168-175.
doi: 10.1016/j.eururo.2017.03.036. Epub 2017 Apr 8.

Validation of a Genomic Risk Classifier to Predict Prostate Cancer-specific Mortality in Men with Adverse Pathologic Features

R Jeffrey Karnes  1 , Voleak Choeurng  2 , Ashley E Ross  3 , Edward M Schaeffer  4 , Eric A Klein  5 , Stephen J Freedland  6 , Nicholas Erho  2 , Kasra Yousefi  2 , Mandeep Takhar  2 , Elai Davicioni  2 , Matthew R Cooperberg  7 , Bruce J Trock  8
Affiliations

Validation of a Genomic Risk Classifier to Predict Prostate Cancer-specific Mortality in Men with Adverse Pathologic Features

R Jeffrey Karnes et al. Eur Urol. 2018 Feb.

Abstract

Background: Risk of prostate cancer-specific mortality (PCSM) is highly variable for men with adverse pathologic features at radical prostatectomy (RP); a majority will die of other causes. Accurately stratifying PCSM risk can improve therapy decisions.

Objective: Validate the 22 gene Decipher genomic classifier (GC) to predict PCSM in men with adverse pathologic features after RP.

Design, setting, and participants: Men with adverse pathologic features: pT3, pN1, positive margins, or Gleason score >7 who underwent RP in 1987-2010 at Johns Hopkins, Cleveland Clinic, Mayo Clinic, and Durham Veteran's Affairs Hospital. We also analyzed subgroups at high risk (prostate-specific antigen >20 ng/ml, RP Gleason score 8-10, or stage >pT3b), or very high risk of PCSM (biochemical recurrence in<2 yr [BCR2], or men who developed metastasis after RP [MET]).

Outcome measurements and statistical analysis: Logistic regression evaluated the association of GC with PCSM within 10 yr of RP (PCSM10), adjusted for the Cancer of the Prostate Risk Assessment Postsurgical Score (CAPRA-S). GC performance was evaluated with area under the receiver operating characteristic curve (AUC) and decision curves.

Results and limitations: Five hundred and sixty-one men (112 with PCSM10), median follow-up 13.0 yr (patients without PCSM10). For high GC score (> 0.6) versus low-intermediate (≤ 0.6), the odds ratio for PCSM10 adjusted for CAPRA-S was 3.91 (95% confidence interval: 2.43-6.29), with AUC=0.77, an increase of 0.04 compared with CAPRA-S. Subgroup odds ratios were 3.96, 3.06, and 1.95 for high risk, BCR2, or MET, respectively (all p<0.05), with AUCs 0.64-0.72. GC stratified cumulative PCSM10 incidence from 2.8% to 30%. Combined use of case-control and cohort data is a potential limitation.

Conclusions: In a large cohort with the longest follow-up to date, Decipher GC demonstrated clinically important prediction of PCSM at 10 yr, independent of CAPRA-S, in men with adverse pathologic features, BCR2, or MET after RP.

Patient summary: Decipher genomic classifier may improve treatment decision-making for men with adverse or high risk pathology after radical prostatectomy.

Keywords: Adverse pathologic features; CAPRA-S; Genomic classifier; Prostate cancer-specific mortality; Radical prostatectomy.

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Conflict of interest statement

Financial disclosures: Bruce J. Trock certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Trock has been a consultant to GenomeDx Biosciences, and has received research grant support from Myriad Genetics, Inc.; Ross, Schaeffer, and Cooperberg have been consultants to GenomeDx Biosciences; Choeurng, Erho, Yousefi, Takhar, and Davicioni are employees of GenomeDx Biosciences.

Figures

Fig. 1
Fig. 1. Area under the receiver operating characteristic curve for the models of prostate cancer-specific mortality within 10 yr in all patients
CAPRA-S = Cancer of the Prostate Risk Assessment Postsurgical Score; CI = confidence interval.
Fig. 2
Fig. 2. Decision curve analysis for the models of prostate cancer-specific mortality within 10 yr in all patients
CAPRA-S = Cancer of the Prostate Risk Assessment Postsurgical Score.
See this image and copyright information in PMC

Comment in

References

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