Long-Term Outcomes and Surgical Conversion After Immunotherapy in Microsatellite Instability-H Biliary Tract Cancers
Year: 2026
Type: article
Study design: Observational Study
Abstract: PURPOSE: Deficient mismatch repair/microsatellite instability (dMMR, MSI-H) in biliary tract cancers (BTCs) is observed in 1%-5% of tumors. MSI-H across solid tumors has demonstrated durable response to immune checkpoint inhibitors (ICIs) regardless of the anatomic location. Here, we describe clinical outcomes and surgical conversion of MSI-H BTC treated with ICIs. PATIENTS AND METHODS: We conducted a multicenter, retrospective analysis of BTC patients with dMMR/MSI-H between 2017 and 2024 at Mayo Clinic, University of Michigan, and University Hospitals Seidman Cancer Center. Outcomes of interest were surgical resection rate, rate of pathologic response, 2-year overall survival (OS; time from initiation of treatment to death/last follow-up), and time to treatment discontinuation (TTD; time from initiation of treatment to cessation because of any cause). Analyses were descriptive. RESULTS: Thirty patients with MSI-H BTC were identified: 19 with cholangiocarcinoma, three with gallbladder cancer, and 8 with BTC undefined. The median age at diagnosis was 61.5 years (range, 26-86). Twenty-six (86.7%) patients had advanced stage at diagnosis. Twenty-seven patients (90%) received first-line systemic therapy, and 13 (48.1%) continued onto second line. Six patients (23.1%) were restaged to resectable from advanced disease after ICI therapy and underwent resection; all remained recurrence-free at last follow-up. Of these six patients, 3 (50%) achieved a pathologic complete response. Among those receiving first-line therapy, the median TTD was 9.9 months (95% CI, 5.7 to 14.5 months) and the 2-year OS was 73% (95% CI, 56% to 94%). CONCLUSION: ICI therapy in patients with MSI-H BTC demonstrated durable response and downstaged some BTC to a resectable stage. dMMR/MSI-H should be performed up-front to guide treatment decisions.
Source: JCO Precision Oncology
DOI: 10.1200/po-25-01156
Authors: Priyanshi Shah, Anina Peersen, Vaibhav Sahai, Amit Mahipal, Nikolas Naleid, Mitesh Borad, Tanios Bekaii-Saab, Mohamad Bassam Sonbol, Umair Majeed, Hani M. Babiker, Conor D.J. O'Donnell, Midhun Malla, Garima Gupta, Caitlyn B. Conboy, Lionel Kankeu Fonkoua, Leslie A. Washburn, Thorvardur R. Halfdanarson, Nicole Peterson, Robert R. McWilliams, Ryan M. Carr, Rondell P. Graham, Patrick Starlinger, Rory Smoot, Susanne Warner, Sumera I. Ilyas, Gregory J. Gores, Lewis Roberts, Julie Heimbach, Fang-Shu Ou, Nguyen H. Tran
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7167927107