免疫细胞浸润在接受根治性放化疗的肌层浸润性膀胱癌中的预后意义：RTOG 0524 和 RTOG 0712 的二次分析

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.