Abstract 1408P
Background
We performed a large-scale comparative transcriptome analysis between an EA and NA cohort of localized PCa to interrogate for demographic-specific differences in molecular profiles that could account for tumor aggression and poor survival.
Methods
We utilized a cohort of 162 EA PCa patients who were treated at a single institution between 2006 to 2021. Tumors were sampled from diagnostic biopsies following central review of the Gleason score (GS) and tumor cellularity by an expert pathologist, then profiled using the Decipher transcriptome assay. Propensity-score matching (PSM) to 100,529 NA cases from the Decipher GRID database (Veracyte, CA) yielded a PSM cohort of 810 NA PCa for comparative analyses of 273 gene-signatures, including the 22-gene genomic classifier (GC). Distant metastasis-free survival (DMFS) was used for survival analyses.
Results
The EA cohort comprised of 38 (23%) NCCN-defined low-/favorable intermediate-, 22 (14%) unfavorable intermediate-, and 102 (63%) high-/very high-risk PCa. 92 (57%) and 70 (43%) patients were classified as GC low/intermediate- (≤0.6) and high-risk (>0.6), respectively. GC high-risk was associated with inferior DMFS (HR 3.53 [95%CI:0.9–13.3], P=0.06). Comparisons between the EA, PSM and full (unmatched) NA cohorts revealed a lower proportion of ERG+ (14% vs 31% vs 41%, P<0.001), PTEN loss (7% vs 20% vs 14%, P<0.001), and AR average/high (64% vs 75% vs 90%, P<0.001) PCa, while proportions of luminal-basal PCa were comparable between the EA and PSM NA cohorts. Interrogation of the tumor microenvironment revealed lower angiogenesis, lower effector T cell activation, and higher immune suppression (MDSC, Treg, and PDL2) signature scores in EA than NA PCa, with largest differences observed in luminal B PCa. Luminal B and PCa with high angiogenesis scores had worse DMFS (HR 2.98 [0.9-10.2]; HR 6.06 [1.3-28.2], respectively) in the EA cohort.
Conclusions
Herein, we validated the Decipher GC for prognostication, and using a large reference population of NA PCa tumors, identified several demographic-specific transcriptomic features, which may have implications on the efficacy of new therapeutic agents in EA men with PCa.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Medical Research Council Singapore Clinician Scientist Award (NMRC/CSA-INV/0027/2018, CSAINV20nov-0021), National Research Foundation Proton Competitive Research Program (NRF-CRP17-2017-05), Ministry of Education Tier 3 Academic Research Fund (MOE2016-T3-1-004), the Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme, NCCS Cancer Fund, and the Kua Hong Pak Head and Neck Cancer Research Programme.
Disclosure
M.L.K. Chua: Financial Interests, Institutional, Invited Speaker: Varian, AstraZeneca, Janssen, Pfizer, MSD; Financial Interests, Institutional, Other, Research agreement: Decipher Biosciences; Non-Financial Interests, Leadership Role: Head and Neck Cancer International Group. R. Kanesvaran: Financial Interests, Institutional, Invited Speaker: Astellas, Johnson and Johnson, Ipsen, Amgen, BMS, MSD, Novartis, AstraZaneca, Sanofi; Financial Interests, Institutional, Advisory Board: Johnson and Johnson, Pfizer, Ipsen, Amgen, BMS, MSD, Bayer, AstraZaneca, Ferring; Financial Interests, Institutional, Research Grant: Sanofi, Eisai, Johnson and Johnson; Non-Financial Interests, Leadership Role, Past President: Singapore Society of Oncology; Non-Financial Interests, Leadership Role, President: SIOG; Non-Financial Interests, Leadership Role, Vice Chairman: Singapore Cancer Society; Non-Financial Interests, Leadership Role, Medical Advisory Board Member: International Kidney Cancer Coalition. All other authors have declared no conflicts of interest.