LAUSR

INTRODUCTION AND OBJECTIVE: Tissue based prognostic signatures have been used in various stages of prostate cancer, including biopsy tissue from men who are deciding between active surveillance versus treatment. Recent studies have suggested that these tests may be affected by tumor heterogeneity impacting their performance for appropriate risk stratification. We evaluated the performance of tissue based prognostic signatures on biopsy tissue from two ongoing prospective trials in men with prostate cancer at the University of Miami. METHODS: The positive cancers cores in Miami Active Surveillance Trial (MAST) and diagnostic and targeted biopsies in BlastEM trial are sent for genomic sequencing.This study reports on preliminary results from both trials on men whose biopsy cores were sequenced at GenomeDx, and evaluated for three commercially available gene signatures (GenomeDx Decipher Genomic classifier, Oncotype Dx Genomic Prostate Score, and Myriad Prolaris Cell Cycle Progression Score). RESULTS: The current cohort consists of 78 men from the MAST (n[46) and BlastEM (n[32) trials whose 231 biopsy cores were sent to GenomeDX for genomic sequencing.We found that for each signature there was a trend toward higher scores with higher grade groups, however each signature displayed a significant degree of variation within each grade group (p<0.001)(Figure 1). When assessing genomic scores from different cores we found significant variability (figure 2) with the level of genomic risk within each biopsy session changing by 25-62% depending on which core was sequenced and which signature was used. Typically in clinical utility genomic score is used for highest grade of the tumor. But we found that on an average 80 % of the time the highest genomic score did not come from the highest grade group in all the three commercially available gene signatures. CONCLUSIONS: There exists a significant degree of genomic heterogeneity between biopsy cores .This may have implications when considering the reliability of these signatures in biopsy tissue. Source of Funding: None