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218MO Comparison of a 22-Gene Genomic Classifier (GC) with NCCN for Risk Stratification of Asian Prostate Cancers (Pca)

Annals of oncology(2020)

NCCS Natl Canc Ctr Singapore

Cited 2|Views30
Abstract
Stratifying intermediate and high risk PCa is challenging due to the clinical heterogeneity of the disease. A 22-gene genomic classifier (GC) has demonstrated clinical utility in influencing treatment decisions in white and non-white men with PCa from Western cohorts. Here, we compared the GC with NCCN for risk stratification in an East-Asian PCa cohort. GC (Decipher Biosciences, San Diego, CA) was performed on diagnostic biopsies or radical prostatectomy (RP) specimens in a pilot cohort (N=31). Gleason’s score (GS) and cellularity were reviewed by GU pathologist; RNA was extracted from 2 x 2.0-mm tumour cores using AllPrep DNA/RNA FFPE Kit and gene expression was performed on Affymetrix Decipher Biosciences array. One (3.2%), 6 (19.4%), 9 (29.0%) and 10 (32.3%) were defined as NCCN low- (LR), intermediate- (IR), high- (HR) and very high-risk (VHR), respectively; 5 (16.1%) presented with M1 at diagnosis. The 22-gene GC classified one (3.2%), 7 (22.6%) and 23 (74.2%) as LR (<0.45), IR (0.45-0.6) and HR (>0.6), [hp2] [AS3] respectively. All M1 PCa patients harbored high GC scores (range 0.796-0.955). Of the 9 NCCN HR patients, 5 (55.6%) were downgraded to GC-IR; while the VHR patients were not affected. For the 6 NCCN IR patients, 4 (66.7%) in fact harbored high GC scores (0.6336-0.7458). Variance in GC scores was highest in GS 6-7 tumors (GC range: 0.3594-0.7458). Using the six-tier combined NCCN-GC risk grouping (Spratt et al.), 4 (66.7%) and 1 (16.7%) of 6 IR patients were reclassified as HR and LR, respectively. 4 (44.4%) of 9 HR who were GC-IR were classified as NCCN-CG HR, but 5 (55.6%) patients who were GC-HR were upgraded to NCCN-CG VHR. Lastly, transcriptome profiling by PAM50 signature revealed a higher proportion of basal than luminal subtypes in our East-Asian cohort (25 [80.6%] vs 6 [19.4%]) and a low proportion of ETS+/ERG+/SPINK1+ PCa (4 [12.9%]). Here, we present our preliminary data suggesting the utility of GC in precise risk stratification of Asian PCa patients. A follow-up study is warranted to investigate the accuracy of the NCCN-GC risk grouping in predicting survival and influencing treatment decision making in Asian men with PCa.
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