Significance of next-generation sequencing in the era of targeted therapy for biliary tract cancer: an analysis at a single institution

Aim: Treatment approaches for biliary tract cancer (BTC) vary widely. Genomic profiling through next-generation sequencing (NGS) has made it possible to apply precision medicine in the management of BTC. This retrospective observational study aimed to evaluate the implementation of treatments based on identified genomic mutations and their clinical significance in patients with BTC in Japan, where NGS is covered by health insurance. Methods: We conducted a retrospective analysis of 65 patients with unresectable or recurrent BTC who underwent comprehensive genomic profiling at a single institution between November 2019 and October 2024. Genomic mutations were classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) scale. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Among the 65 patients, clinically relevant genomic mutations classified using the ESCAT scale were identified in 47 patients, and clinically treatable genomic mutations were identified in 13 patients. Six patients ultimately received mutation-guided therapy, including fibroblast growth factor receptor inhibitors and pembrolizumab. The median time from specimen submission to review by the expert panel was 26 (range, 16–40) days. No significant difference in OS was observed based on the site of the primary tumor (log-rank test, P = 0.5804). Conclusions: Although clinically actionable genomic mutations were identified in one-fifth of patients, < 10% ultimately received treatment based on those findings, highlighting a gap between genomic profiling and treatment implementation. In contrast, with the increasing number of available therapies, access to precision treatment for patients with BTC may improve in the future through a combination of early adoption of NGS and the complementary use of liquid biopsy when tissue is unavailable.