Abstract 4471: Commercial gene expression tests for prostate cancer prognosis provide paradoxical estimates of race-specific risk

Abstract

Abstract Background: Current National Comprehensive Cancer Network (NCCN) guidelines recommend three gene expression-based tests for prostate cancer (PCa) prognosis in men with low or favorable intermediate risk disease: Decipher, Oncotype DX Prostate, and Prolaris. The three tests feature varying numbers of genes with minimal overlap. Importantly, development and validation efforts for all three panels were undertaken in predominantly European American men (EAM) cohorts, and limited research exists on the value of such signatures in African American men (AAM), who have poorer PCa outcomes. Here, we explored differences in gene expression between EAM and AAM for the three panels recommended by the NCCN for PCa prognosis. Methods: 232 EAM and 95 AAM patients provided radical prostatectomy specimens. Gene expression was quantified using Nanostring for 60 genes spanning the Oncotype DX Prostate, Prolaris, and Decipher panels. Differential expression and intrapanel co-expression by race were assessed using Mann-Whitney tests and Spearman’s correlations, respectively. A continuous expression-based risk score was approximated for each panel with higher scores indicating worse outcomes. Race-specific risks were compared using Mann-Whitney tests and Spearman’s correlations. Results: Clinical and pathologic features were similar between AAM and EAM. Differential expression by race was observed for 48% of genes measured, though the magnitudes of expression differences were small. Co-expression patterns were more strongly preserved by race group for Oncotype DX and Decipher versus Prolaris (integrative correlations of 0.87, 0.73, and 0.62, respectively). Paradoxically, poorer prognosis was estimated in EAM versus AAM for Prolaris and Oncotype DX (p = 0.01 for both), whereas worse prognosis was predicted for AAM versus EAM using Decipher (p < 0.001). Discussion: Due to observed racial differences across three commercial gene expression panels for PCa prognosis, caution is warranted when applying these panels in clinical decision-making in AAM. Replication of our findings directly on the commercial panels with long-term follow-up is warranted. Citation Format: Jordan H. Creed, Anders E. Berglund, Robert J. Rounbehler, Shivanshu Awasthi, John L. Cleveland, Jong Y. Park, Kosj Yamoah, Travis A. Gerke. Commercial gene expression tests for prostate cancer prognosis provide paradoxical estimates of race-specific risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4471.