Does CDH1 Mutation Status Affect Treatment Efficacy in Urothelial Bladder Cancer?

By: Kayci Reyer
Posted: Monday, July 17, 2023

According to findings presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 4587), the presence of CDH1 mutations in patients with urothelial bladder cancer may predict resistance to some types of treatment, such as immune checkpoint inhibitor therapy, but not others, such as systemic chemotherapy. Previously associated with plasmacytoid histology, urothelial bladder cancer may also feature other unique genomic markers, including higher microsatellite instability and tumor mutational burden.

“These findings support [comprehensive genomic profiling] to guide therapeutic approaches based on the personalized genomic signature of [urothelial bladder cancer],” concluded Philippe E. Spiess, MD, of Moffitt Cancer Center, Tampa, Florida, and colleagues.

The study included two cohorts of patients with urothelial bladder cancer. The first cohort comprised 6,676 patients with clinically advanced disease who experienced hybrid capture-based comprehensive genomic profiling and immunohistochemistry. The second cohort included 586 patients who underwent a real-world clinical outcome study based on de-identified information from the Flatiron Health–Foundation Medicine urothelial clinicogenomic database.

A total of 217 patients in cohort 1 had CDH1-mutated disease, with plasmacytoid histology occurring in 65.2%. Microsatellite instability, mean tumor mutational burden, and genomic alterations in RB1, PTEN, and PIK3CA were found to be higher among patients with CDH1 mutations, whereas genomic loss of heterozygosity, FGFR3 alteration, and loss of CDKNA and MTAP were lower among patients with CDH1 mutations. In cohort 2, CDH1 mutations occurred in 22 patients. The presence of this mutation was associated with poorer outcomes in real-world progression-free and overall survival in patients who received immune checkpoint inhibitor therapy, whereas no adverse survival impact related to CDH1 mutation status was noted among patients receiving chemotherapy.