Clinical Utility and Genomic Landscape of Comprehensive Genomic Profiling in Biliary Tract Tumors: A Single-Center Real-World Study

Background: Comprehensive genomic profiling (CGP) is increasingly incorporated into the management of biliary tract tumors (BTTs); however, single-center real-world data integrating clinical utility and site-specific genomic landscape remain limited. Methods: This retrospective single-center observational study included 91 patients with BTTs who underwent CGP. The primary endpoints were the rates of potentially actionable genomic alterations, expert panel-based therapeutic options, and implementation of genomically matched therapy. Secondary endpoints included the distribution of recurrent and clinically relevant genomic alterations according to the primary tumor site. Results: The cohort included 46 patients with intrahepatic cholangiocarcinoma (iCCA), 19 with extrahepatic cholangiocarcinoma (eCCA), 24 with gallbladder cancer (GBC), and 2 with ampullary tumors. CGP was successfully performed in all 91 patients. Reportable genomic alterations were detected in 88 patients (96.7%), whereas no reportable alteration was detected in three patients (3.3%). The most frequently altered genes were TP53 (51/91, 56.0%), KRAS (21/91, 23.1%), CDKN2A (18/91, 19.8%), SMAD4 (14/91, 15.4%), and ARID1A/PBRM1 (12/91, 13.2%). Potentially actionable genomic alterations were identified in 21 patients (23.1%). Expert panel-based therapeutic options were identified in 15 patients (16.5%), and genomically matched therapy was introduced in 7 patients (7.7%). Matched therapy was introduced the most frequently in iCCA (6/46, 13%), followed by GBC (1/24, 4.2%), whereas no patient with eCCA or ampullary tumor received matched therapy. Conclusions: CGP revealed a heterogeneous genomic landscape across BTT subtypes and provided clinically actionable information in a limited but meaningful subset of patients. The practical utility of CGP was the greatest in selected molecular subsets, particularly iCCA.