Gene expression signatures in biopsy cores as predictors of coexisting higher-grade disease in Gleason group 1 prostate cancer: Results from the Miami MAST prospective clinical trial.

239 Background: Despite several improvements in Active Surveillance (AS), pathologic reclassification remains frequent. Therefore, we examined if gene expression signatures in biopsy cores with Gleason Group (GG) 1 cancer can predict coexisting higher-grade disease elsewhere in the prostate among participants of the Miami Active Surveillance Trial (MAST). Methods: MAST enrolled 205 men with low and favorable intermediate-risk prostate cancer undergoing AS. Participants underwent an MRI and confirmatory biopsy at enrollment, and annually thereafter for three years. Positive cores underwent expression profiling with the whole-transcriptome Decipher genomic classifier (DGC). Derived Genomic Prostate Score (dGPS) and Cell Cycle Progression (dCCP) signatures were obtained. The primary objective was to compare signature scores in GG1 cores from prostates with (positive) vs. without (negative) coexisting GG2+ cancer elsewhere. The three signatures were also compared for coexisting GG3+ cancer elsewhere, and a sub-analysis using only the highest-volume GG1 core from each biopsy session was performed. Results: There was no significant difference between groups in DGC or dCCP scores regarding the primary objective, whereas median (IQR) dGPS was 0.14 (0.08–0.24) in positive vs. 0.10 (0.07–0.16) in negative groups (p=0.018). For coexisting GG3+ elsewhere, DGC or dCCP scores again did not differ, while dGPS was 0.24 (0.19–0.29) vs. 0.10 (0.07–0.16) in positive and negative groups, respectively (p=0.005). In a sub-analysis using only the highest volume GG1 core from each biopsy, as is the usual standard of care when using genomic testing on biopsy tissue, there was no significant difference in score between the groups for any of the signatures. Conclusions: Neither Decipher GC, dCCP, nor dGPS signatures showed clinically significant differences between GG1 cores with vs. without coexisting higher-grade cancer elsewhere when using the highest volume GG1 core for genomic testing. Our findings suggest that prostate cancer foci are heterogeneous and genomically independent. Clinical trial information: NCT02242773 .