Long-Term Outcomes and Surgical Conversion After Immunotherapy in Microsatellite Instability-H Biliary Tract Cancers

Area of Science:

• Oncology
• Gastroenterology
• Immunotherapy

Background:

• Deficient mismatch repair/microsatellite instability (dMMR/MSI-H) occurs in 1%-5% of biliary tract cancers (BTCs).
• Immune checkpoint inhibitors (ICIs) have shown efficacy in MSI-H solid tumors across various cancer types.
• The role of ICIs in MSI-H BTC, particularly for surgical conversion, requires further investigation.

Purpose of the Study:

• To evaluate the clinical outcomes of patients with MSI-H BTC treated with ICIs.
• To assess the surgical conversion rate and pathologic response in MSI-H BTC after ICI therapy.
• To determine overall survival (OS) and time to treatment discontinuation (TTD) in this patient cohort.

Main Methods:

• A multicenter, retrospective analysis of 30 patients with dMMR/MSI-H BTC treated between 2017 and 2024.
• Data collected included surgical resection rates, pathologic response, 2-year OS, and TTD.
• Descriptive analyses were performed to summarize outcomes.

Main Results:

• Six of 30 patients (23.1%) with advanced MSI-H BTC were downstaged to resectable disease after ICI therapy and underwent successful resection.
• Three of these six patients (50%) achieved a pathologic complete response, remaining recurrence-free.
• The median TTD was 9.9 months, and the 2-year OS was 73% for patients receiving first-line ICI therapy.

Conclusions:

• ICI therapy offers durable responses and can facilitate surgical resection in select patients with MSI-H BTC.
• Up-front dMMR/MSI-H testing is crucial for guiding treatment decisions in BTC.
• ICIs represent a promising therapeutic strategy for patients with MSI-H BTC, potentially enabling curative-intent surgery.