IBCN 2018: Novel Immune Basal Subtypes to Predict Pathologic Response to Chemotherapy and Survival Benefit in Muscle-Invasive Bladder Cancer

Rotterdam, The Netherlands (UroToday.com) Woonyoung Choi, Ph.D. presented his team's work on immune basal subtypes in response to chemotherapy and survival. Using gene expression profiling, molecular subtypes are enriched with clinically actionable features in muscle-invasive bladder cancer (MIBC). To further explore the granular features of the subtypes, Dr. Choi and team extended their prior 3 subtypes (basal, luminal and p53-like) into 5 subtypes in TCGA MIBC dataset.

Since activated PPARg and FGFR3 mutation can be distinctive therapeutic targets in luminal tumors, luminal subtype was divided into two novel luminal subtypes using FGFR3 signature – luminal-papillary and LP. Using immune infiltration markers that are known as prognostic values in multiples solid tumors, two novel immune subtypes within basal MIBC were identified – basal immune enriched (BIE) and basal immune suppressed (BIS). Further investigation of immunogenomics signatures in each subtype shows BIE subtype was enriched with tumor-infiltrating lymphocytes and IFNg signature compared to other subtypes. BIE had significantly improved survival outcomes while BIS still remained the subtype with the worst survival outcomes. Since immune activation has been associated with the response to chemotherapy, the potential significance of novel immune subtypes was further explored using a meta-dataset consisting of 148 TUR specimens from patients who received neoadjuvant chemotherapy (NAC) followed by radical cystectomy. In this cohort, chemotherapy was active as measured by an overall pathological downstaging rate (≤pT1 at cystectomy) of 47% (70/148). Based on pathological downstaging rate, BIE was the most responsive to chemotherapy (response rate; 80%, P<0.001) while BIS and p53-like tumors were resistant to chemotherapy (response rate; 24% and 26%, respectively, P<0.001). In addition, BIE patients had the best survival outcomes (median OS: 211 months, P = 0.05) among subtypes. These results demonstrate that we have first discovered the association between molecular subtype and pathological response to NAC and suggest that it is possible to prospectively identify the patients who most likely will benefit from NAC. Further understanding of the location of where T cells arise and the exact biologic mechanisms are needed. 

Presented by: Woonyoung Choi, MS, Ph.D., Johns Hopkins School of Medicine, Baltimore, MA

Written by: Stephen B. Williams, M.D., Associate Professor, Division of Urology, The University of Texas Medical Branch, Galveston, TX. and Ashish M. Kamat, M.D. Professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX at the 16th Annual Meeting of the International Bladder Cancer Network (IBCN) October 11-13, 2018 - the Inntel Hotels Rotterdam Centre, Rotterdam, The Netherlands