218MO - Comparison of a 22-gene genomic classifier (GC) with NCCN for risk stratification of Asian prostate cancers (PCa)

Background

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.

Methods

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.

Results

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%]).

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Medical Research Council (NMRC), Decipher Biosciences (Structured research agreement).

Disclosure

E. Davicioni: Leadership role, Full/Part-time employment, Chief Scientific Officer: Decipher Biosciences. M.L.K. Chua: Research grant/Funding (institution): Decipher BioSciences. All other authors have declared no conflicts of interest.