Prognostic Significance of Immune Cell Infiltration in Muscle-invasive Bladder Cancer Treated with Definitive Chemoradiation: A Secondary Analysis of RTOG 0524 and RTOG 0712

Zaker Rana; Sophia C Kamran; Amol C Shetty; Philip Sutera; Yang Song; Soha Bazyar; Abhishek A Solanki; Jeffry P Simko; Alan Pollack; David McConkey; Max Kates; M Minhaj Siddiqui; Jeffrey Hiken; Jon Earls; David Messina; Kent W Mouw; David Miyamoto; William U Shipley; M Dror Michaelson; Anthony Zietman; John J Coen; Douglas M Dahl; Ashesh B Jani; Luis Souhami; Brian K Chang; R Jeffrey Lee; Huong Pham; David T Marshall; Xinglei Shen; Stephanie L Pugh; Felix Y Feng; Jason A Efstathiou; Phuoc T Tran; Matthew P Deek

doi:10.1016/j.euo.2024.03.015

Prognostic Significance of Immune Cell Infiltration in Muscle-invasive Bladder Cancer Treated with Definitive Chemoradiation: A Secondary Analysis of RTOG 0524 and RTOG 0712

Eur Urol Oncol. 2024 Apr 18:S2588-9311(24)00095-6. doi: 10.1016/j.euo.2024.03.015. Online ahead of print.

Authors

Zaker Rana¹, Sophia C Kamran², Amol C Shetty³, Philip Sutera⁴, Yang Song³, Soha Bazyar⁵, Abhishek A Solanki⁶, Jeffry P Simko⁷, Alan Pollack⁸, David McConkey⁹, Max Kates⁹, M Minhaj Siddiqui⁵, Jeffrey Hiken¹⁰, Jon Earls¹⁰, David Messina¹⁰, Kent W Mouw¹¹, David Miyamoto², William U Shipley², M Dror Michaelson², Anthony Zietman², John J Coen¹², Douglas M Dahl², Ashesh B Jani¹³, Luis Souhami¹⁴, Brian K Chang¹⁵, R Jeffrey Lee¹⁶, Huong Pham¹⁷, David T Marshall¹⁸, Xinglei Shen¹⁹, Stephanie L Pugh²⁰, Felix Y Feng²¹, Jason A Efstathiou², Phuoc T Tran²², Matthew P Deek²³

Affiliations

¹ University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA.
² Massachusetts General Hospital Cancer Center, Boston, MA, USA.
³ University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Johns Hopkins University, Baltimore, MD, USA.
⁵ University of Maryland, Baltimore, MD, USA.
⁶ Loyola University Medical Center, Maywood, IL, USA.
⁷ UCSF Medical Center-Mount Zion, San Francisco, CA, USA.
⁸ University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, FL, USA.
⁹ Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Cancer Center, Baltimore, MD, USA.
¹⁰ CoFactor Genomics, San Francisco, CA, USA.
¹¹ Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
¹² Department of Radiation Oncology, GenesisCare USA-Warwick, Warwick, RI, USA.
¹³ Emory University Hospital/Winship Cancer Institute, Atlanta, GA, USA.
¹⁴ McGill University Health Centre Research Institute, Montreal, Canada.
¹⁵ Parkview Regional Medical Center, Fort Wayne, IN, USA.
¹⁶ Intermountain Medical Center, Murray, UT, USA.
¹⁷ Virginia Mason Medical Center, Seattle, WA, USA.
¹⁸ Medical University of South Carolina, Charleston, SC, USA.
¹⁹ University of Kansas Cancer Center, Kansas City, KS, USA.
²⁰ NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA.
²¹ UCSF Medical Center-Mission Bay, San Francisco, CA, USA.
²² University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA. Electronic address: phuoc.tran@som.umaryland.edu.
²³ Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address: matthewdeek@gmail.com.

PMID: 38641541
DOI: 10.1016/j.euo.2024.03.015

Abstract

Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26-1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24-0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40, 95% CI 0.21-0.75; p = 0.005) and OS (HR 0.49, 95% CI 0.25-0.94; p = 0.033). Higher IDO1 expression (IFNγ signature) was also associated with longer DFS (HR 0.44, 95% CI 0.24-0.88; p = 0.021) and OS (HR 0.49, 95% CI 0.24-0.99; p = 0.048). These findings should be validated in prospective CRT trials that include biomarkers, particularly for trials incorporating immunotherapy for MIBC. PATIENT SUMMARY: We analyzed patient samples from two clinical trials (NRG/RTOG 0524 and 0712) of chemoradiation for muscle-invasive bladder cancer using a novel method to assess immune cells in the tumor microenvironment. Higher expression of genes associated with immune activation and high overall immune-cell content were associated with better disease-free survival and overall survival for patients treated with chemoradiation.

Keywords: Bladder cancer; Chemoradiation; Immune cell infiltration.

Abstract

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