Integrating molecular screening into the management of cholangiocarcinoma patients: a real-world perspective

Introduction More than one-third of patients with locally advanced or metastatic cholangiocarcinoma (CCA) would exhibit actionable genomic alterations. We wanted to evaluate the theragnostic impact of molecular sequencing on the management of patients with CCA. Patients and methods All patients with CCA who underwent next-generation sequencing panel testing at the University Hospital of Bordeaux between January 2021 and October 2023 were retrospectively included. Clinical outcomes, including overall survival (OS), progression-free survival (PFS) and treatment tolerability, were analysed. Results Among our 88 patients, 27.3% harboured actionable genetic alterations (27.6% with intrahepatic CCA (iCCA) and 26.7% with other localisations), and 11.4% received targeted therapy (15.5% with iCCA and 2.5% with other localisations). No significant benefit in OS or PFS was observed for patients with identified molecular alterations (p=0.28 and p=0.52, respectively), nor for patients who received a targeted therapy (p=0.11 and 0.23, respectively). Conclusion Our real-world study demonstrated a lower frequency of actionable molecular targets in patients with CCA and limited access to targeted therapies. These patients had nevertheless favourable clinical outcomes, emphasising the critical need for the development of novel and efficacious therapeutic combinations.