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.
European urology oncology. 2024 Apr 18 [Epub ahead of print]
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
University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA., Massachusetts General Hospital Cancer Center, Boston, MA, USA., University of Maryland School of Medicine, Baltimore, MD, USA., Johns Hopkins University, Baltimore, MD, USA., University of Maryland, Baltimore, MD, USA., Loyola University Medical Center, Maywood, IL, USA., UCSF Medical Center-Mount Zion, San Francisco, CA, USA., University of Miami Miller School of Medicine-Sylvester Cancer Center, Miami, FL, USA., Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Cancer Center, Baltimore, MD, USA., CoFactor Genomics, San Francisco, CA, USA., Dana-Farber/Harvard Cancer Center, Boston, MA, USA., Department of Radiation Oncology, GenesisCare USA-Warwick, Warwick, RI, USA., Emory University Hospital/Winship Cancer Institute, Atlanta, GA, USA., McGill University Health Centre Research Institute, Montreal, Canada., Parkview Regional Medical Center, Fort Wayne, IN, USA., Intermountain Medical Center, Murray, UT, USA., Virginia Mason Medical Center, Seattle, WA, USA., Medical University of South Carolina, Charleston, SC, USA., University of Kansas Cancer Center, Kansas City, KS, USA., NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA., UCSF Medical Center-Mission Bay, San Francisco, CA, USA., University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA. Electronic address: ., Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. Electronic address: .