Outcomes After Resection for Multiple Intrahepatic Cholangiocarcinoma—A National Population-Based Study

BACKGROUND: Tumor multiplicity is a negative prognostic factor in intrahepatic cholangiocarcinoma (iCCA) and the role of surgical resection in multiple iCCA remains unclear. PATIENTS AND METHODS: Data were extracted from the Swedish quality registry for cancers of the liver and biliary tract, for all patients undergoing surgery for iCCA (2010-2021). Validation was performed with all Swedish hepatobiliary referral centers, including a comparison cohort of patients with liver-only multiple iCCA and nonsurgical therapy. The primary endpoint was overall survival (OS). RESULTS: Out of 338 patients operated for iCCA, 284 had resectable tumors and 54 (16.0%) unresectable disease at exploration. In the resection and exploration groups, 46 (16.2%) and 11 patients (20.4%), respectively, had multiple lesions. A majority of patients with resection for multiple iCCA had two or three lesions (63.0%), with median OS 27.1 months (95% CI 18.8-35.5), compared with 5.3 months (95% CI 3.8-6.8) for patients with unresectable disease (P < 0.001). For patients with four or more lesions, OS with resection was similar as with unresectable disease (P = 0.922). In multiple iCCA, resection was associated with better performance status (P = 0.007), negative lymph nodes (P = 0.028), and smaller tumors (P = 0.004). With adjustment including these factors, resection was not significantly associated with OS (P = 0.090). CONCLUSIONS: Resection for multiple iCCA with four or more lesions was not associated with a survival benefit compared with exploration. With selection to surgery for patients with good performance status, smaller tumors and no signs of lymph node metastasis, resection for two or three lesions yielded median OS above 2 years.