Validation of a genomic classifier for prediction of metastasis and prostate cancer-specific mortality in African-American men following radical prostatectomy in an equal access healthcare setting

Lauren E. Howard, Jingbin Zhang, Nick Fishbane, Amanda M.De Hoedt, Zachary Klaassen, Daniel E. Spratt, Adriana C. Vidal, Dechen Lin, Megan P. Hitchins, Sungyong You, Michael R. Freeman, Kosj Yamoah, Elai Davicioni, Stephen J. Freedland

Research output: Contribution to journalArticle

Abstract

Background: The Decipher 22-gene genomic classifier (GC) may help in post-radical prostatectomy (RP) decision making given its superior prognostic performance over clinicopathologic variables alone. However, most studies evaluating the GC have had a modest representation of African-American men (AAM). We evaluated the GC within a large Veteran Affairs cohort and compared its performance to CAPRA-S for predicting outcomes in AAM and non-AAM after RP. Methods: GC scores were generated for 548 prostate cancer (PC) patients, who underwent RP at the Durham Veteran Affairs Medical Center between 1989 and 2016. This was a clinically high-risk cohort and was selected to have either pT3a, positive margins, seminal vesicle invasion, or received post-RP radiotherapy. Multivariable Cox models and survival C-indices were used to compare the performance of GC and CAPRA-S for predicting the risk of metastasis and PC-specific mortality (PCSM). Results: Median follow-up was 9 years, during which 37 developed metastasis and 20 died from PC. Overall, 55% (n = 301) of patients were AAM. In multivariable analyses, GC (high vs. intermediate and intermediate vs. low) was a significant predictor of metastasis in all men (all p < 0.001). Consistent with prior studies, relative to CAPRA-S, GC had a higher C-index for 5-year metastasis (0.78 vs. 0.72) and 10-year PCSM (0.85 vs. 0.81). There was a suggestion GC was a stronger predictor in AAM than non-AAM. Specifically, the 5-year metastasis risk C-index was 0.86 in AAM vs. 0.69 in non-AAM and the 10-year PCSM risk C-index was 0.91 in AAM vs. 0.78 in non-AAM. However, the test for interaction of race and the performance of the GC in the Cox model was not significant for either metastasis or PCSM (both p ≥ 0.3). Conclusions: GC was a very strong predictor of poor outcome and performed well in both AAM and non-AAM. Our data support the use of GC for risk stratification in AAM post-RP. While our data suggest that GC may actually work better in AAM, given the limited number of events, further validation is needed.

Original languageEnglish (US)
JournalProstate Cancer and Prostatic Diseases
DOIs
StateAccepted/In press - Jan 1 2019

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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    Howard, L. E., Zhang, J., Fishbane, N., Hoedt, A. M. D., Klaassen, Z., Spratt, D. E., Vidal, A. C., Lin, D., Hitchins, M. P., You, S., Freeman, M. R., Yamoah, K., Davicioni, E., & Freedland, S. J. (Accepted/In press). Validation of a genomic classifier for prediction of metastasis and prostate cancer-specific mortality in African-American men following radical prostatectomy in an equal access healthcare setting. Prostate Cancer and Prostatic Diseases. https://doi.org/10.1038/s41391-019-0197-3