@article{05e2149217654c4496adc023b1d28c70,
title = "Novel Transcriptomic Interactions Between Immune Content and Genomic Classifier Predict Lethal Outcomes in High-grade Prostate Cancer",
abstract = "Grade group 4 and 5 (GG-45) prostate cancer (PCa) patients are at the highest risk of lethal outcomes, yet lack genomic risk stratification for prognosis and treatment selection. Here, we assess whether transcriptomic interactions between tumor immune content score (ICS) and the Decipher genomic classifier can identify most lethal subsets of GG-45 PCa. We utilized whole transcriptome data from 8071 tumor tissue (6071 prostatectomy and 2000 treatment-na{\"i}ve biopsy samples) to derive four immunogenomic subtypes using ICS and Decipher. When compared across all grade groups, GG-45 samples had the highest proportion of most aggressive subtype—ICSHigh/DecipherHigh. Subsequent analyses within the GG-45 patient samples (n = 1420) revealed that the ICSHigh/DecipherHigh subtype was associated with increased genomic radiosensitivity. Additionally, in a multivariable model (n = 335), ICSHigh/DecipherHigh subtype had a significantly higher risk of distant metastasis (hazard ratio [HR] = 5.41; 95% confidence interval [CI], 2.76–10.6; p ≤ 0.0001) and PCa-specific mortality (HR = 10.6; 95% CI, 4.18–26.94; p ≤ 0.0001) as compared with ICSLow/DecipherLow. The novel immunogenomic subtypes establish a very strong synergistic interaction between ICS and Decipher in identifying GG-45 patients who experience the most lethal outcomes. Patient summary: In this analysis, we identified a novel interaction between the total immune content of prostate tumors and genomic classifier to identify the most lethal subset of patients with grade groups 4 and 5. Our results will aid in the subtyping of aggressive prostate cancer patients who may benefit from combined immune-radiotherapy modalities.",
keywords = "Aggressive prostate cancer, Decipher score, Genomic risk, Grade group 4, Grade group 5, High-grade prostate cancer, Immune content, Immunogenomics, Lethal outcomes",
author = "Kosj Yamoah and Shivanshu Awasthi and Mahal, {Brandon A.} and Zhao, {Shuang G.} and Grass, {G. Daniel} and Anders Berglund and Julieta Abraham-Miranda and Travis Gerke and Rounbehler, {Robert J.} and Elai Davicioni and Yang Liu and Jong Park and Cleveland, {John L.} and Pow-Sang, {Julio M.} and Daniel Fernandez and Javier Torres-Roca and Karnes, {R. Jeffrey} and Edward Schaeffer and Freedland, {Stephen J.} and Spratt, {Daniel E.} and Den, {Robert B.} and Rebbeck, {Timothy R.} and Felix Feng",
note = "Funding Information: Funding/Support and role of the sponsor: Prostate Cancer Foundation and Department of Defense award (W81XWH-19-1-0435) to Kosj Yamoah, MD, PhD. Funding Information: Financial disclosures: Kosj Yamoah certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Decipher Biosciences has filed a patent on the ICS on which Felix Y. Fang and Shuang G. Zhao are on, in addition to other unrelated patent applications in prostate cancer. Shuang G. Zhao has travel related expense from Decipher Bioscience. Yang Liu and Elai Davicioni are employees of Decipher Biosciences. Javier Torres-Roca has intellectual property (RSI) and stock in Cvergenx. Edward M. Schaeffer has served as a consultant for Decipher Bioscience, OPKO Health, and Abbvie. Stephen J. Freedland reports receiving research funding from Decipher Bioscience, and serving as a consultant for GenomeDx, Astellas, Medivation, Bayer, Sanofi, Janssen, Dendreon, Armune, Parallel 6, Singulex, Boston Scientific, and Churchill. Daniel Spratt has served as a consultant for Dendreon. Robert Den has received research funding and has served as a consultant for Decipher Biosciences. Felix Feng is a co-Founder of PFS Genomics, holds stock options in SerImmune, and has served as a consultant for Astellas, Bayer, Blue Earth, Celgene, EMD Serono, Janssen, Myovant, and Roivant. Publisher Copyright: {\textcopyright} 2020 European Association of Urology",
year = "2020",
doi = "10.1016/j.eururo.2020.11.038",
language = "English (US)",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
}