Pd52-06 computational Immunogenomic Modeling of Immunoevasive Aggressive Prostate Cancer

Abstract

INTRODUCTION AND OBJECTIVE: Molecular subtyping using the PAM50 classifier has demonstrated associations with disease prognosis and treatment response in breast and prostate cancer. This study aims to evaluate whether there are differences between African American (AA) and white men in the predominant cellular lineage of prostate tumors. METHODS: This is an analysis of a pooled cohort comprised of AA or white men with localized prostate cancer treated with radical prostatectomy from the Fred Hutchinson Cancer Research Center (n [501), Eastern Virginia Medical School (n[124), and The Cancer Genome Atlas (n[472). Using previously described PAM50 methodology, a nearest centroid classifier was applied on each dataset and classified tumors into the following three categories based on gene expression data: (1) luminal A, (2) luminal B, and (3) basal. Kaplan-Meier analysis stratified by race was conducted to estimate progression-free survivalddefined as freedom from biochemical failure, metastases, or prostate cancer mortalitydand prostate cancer specific survival. Statistical significance was calculated using the logrank test.RESULTS: In total, 1,097 unique patients were evaluated. AA men represented 13% (n[143) of the dataset. Luminal A was the most common subtype among AA men (50.4%) compared to white men (38.4%, p < 0.001). Basal subtype (16.8% vs. 22.9%, p [ 0.13) and luminal B (32.9% vs. 38.8%, p [ 0.21) were less common among AA men compared to white men, respectively. On univariable analysis, luminal B was associated with lower rates of progression-free survival and prostate cancer specific survival when compared to luminal A and basal tumors (Figure 1, both p < 0.01). These observations remained consistent when stratified by race. The 10-year cumulative freedom from disease progression was 52%, 78.9%, and 73.1% among AA men and 62.2%, 73.1%, and 71.3% among white men, for luminal B, luminal A, and basal subtypes respectively.CONCLUSIONS: AA men demonstrated a higher proportion of luminal A tumors; however, AA men with luminal B tumors had the worse clinical outcomes in a pooled dataset of prostatectomy patients. Larger cohorts enriched for AA men are needed to confirm these results and better understand cellular lineage of prostate cancer by race and its impact on treatment response and cancer-specific survival.