Decipher genomic classifier (DGC) of early prostate cancer (EPC), and underlying transcriptomic profile (TP): American (Am) versus non-American (NA).

414 Background: Data on DGC in EPC, come predominantly from US patients (pts), revealing significant reclassification of NCCN risk Despite its global use, data among NA is scant. We aimed to analyze DGC results and TP among NA versus (vs) Am with EPC. Methods: From the DGC database (Decipher Biosciences Inc), we identified and analyzed the results (risk and TP) of Israeli (Is) vs matched Am pts with EPC. Matching was according to common NCCN clinicopathologic features (T and N stage, Gleason grade, number of adverse pathologic features). Results: Among Is pts, 692 (median age, ma, 69) had a biopsy (bx) DGC, and 115 (ma 67) a post prostatectomy (PP) DGC. Their median DGC in bx was 0.47, and PP 0.78. DGC risk was 45% low, 24% intermediate, 31% high, in bx, and 13% low, 16% intermediate, 71% high, PP. Bx DGC led to reclassification of risk in 33% of pts with clinical NCCN low-favorable intermediate risk, and 48% of pts with clinical NCCN unfavorable intermediate-high risk. Among matched Am, 103,108 (ma 68) had a bx DGC, and 40,906 (ma 65) a PP DGC. Am median DGC was 0.43 in bx, and 0.65 PP. Am DGC risk was 52% low, 20% intermediate, 28% high, in bx, and 28% low, 17% intermediate, 55% high, PP. While NCCN risk grouping was similar between Is vs matched Am (p=1.0), median DGC risk was significantly higher among Is (p<0.001), and the distribution of DGC risk groups significantly different (p=0.004 for bx, p<0.001 PP). A correlative TP analysis revealed greater overall differences of Isi vs matched Am. Significant (p<0.001) differences in bx DGC, included AR status (intact vs deficient), prostate subtype classifier (PSC, luminal differentiated, luminal proliferating, basal immune, basal neuroendocrine), PAM50 (Luminal A, Luminal B, Basal), RSI (1), Cell cycle progression (2), activated CD8, T regulatory cells, angiogenesis (Uhlik), Myeloid derived suppressor cells, Interferon response alpha hallmark, and immune 190. Significant (p<0.001) differences in PP DGC, included AR activity, p53 mutation, PSC, PAM50, SC/NE (adenocarcinoma, neuroendocrine carcinoma (3), RSI, activated CD4 and CD8, T regulatory cells, angiogenesis (Uhlik), tertiary lymphoid structure, PDL2 signature, Myeloid derived suppressor cells, and Interferon response alpha hallmark. Conclusions: In early prostate cancer, as previously reported among American pts, DGC may be an important tool for accurate patients risk assessment, leading to NCCN risk reclassification in a significant proportion, Furthermore, the present study preliminary results suggest that geographic variation DGC may exist, and correlate with differences in transcriptomic profile. 1. Torres-Roca 2009. 2. Cuzick 2011. 3. Beltran 2016.