MP51-03 PROSTATE TUMOR SIZE IS INDEPENDENTLY ASSOCIATED WITH GENOMIC RISK

Abstract

INTRODUCTION AND OBJECTIVE: Unlike many other cancers, primary tumor size has had no role in the management of localized prostate cancer prior to prostatectomy. While tumor size in postprostatectomy specimens is of unclear prognostic importance when adjusted for other factors, magnetic resonance imaging now allows assessment of prostate tumor size in situ. We sought to determine if prostate tumor size was associated with markers of genomic risk as a surrogate for cancer aggressiveness. METHODS: We abstracted tumor size from the primary pathology reports of prostate cancers incorporated in The Cancer Genome Atlas (TCGA). We used RNA-Seq data to estimate the Cell Cycle Progression Score (CCPS, commercially Prolaris ® from Myriad Genetics Inc.), the Genomic Classifier Score (GCS, commercially the Decipher® Score from Decipher Biosciences, Inc.) and the Genomic Prostate Score (GPS, commercially Oncotype Dx ® from Genomic Health, Inc.). We extracted SChLaP1 expression and the percentage of copy number alterations (%CNA). Multivariable regression assessing the relationship between tumor size and genomic risk was performed. We also analyzed differential gene expression associated with tumor size. RESULTS: We included 267 men who had both tumor size and gene expression data available. On univariate linear analysis, tumor size was associated with cCCPS, cGCS, the cGPS, SChLaP1 expression and %CNA (p< 0.01, Figure 1). Tumor size was associated with Gleason grade group on linear regression adjusted for tumor purity and markers of genomic risk (p< 0.01). On multivariable linear regression adjusted for Gleason grade group and tumor purity, tumor size was associated with the cGCS, the cGPS, and SChLaP1 expression (p< 0.05), but not the cCCPS. Gene set enrichment analysis demonstrated that tumors <5 cc, when adjusting for Gleason grade group, were enriched for androgen response genes, while tumors >5 cc were enriched for MYC targets and genes associated with epithelial mesenchymal transition. CONCLUSIONS: Prostate tumor size is independently associated with established markers of genomic risk. These results have important implications for risk stratification in patients undergoing nonextirpative therapies, including the selection of patients for surveillance and adjuvant therapies. (Figure Presented).