Abstract
INTRODUCTION: Recent advancements in systemic chemotherapy have fueled debates regarding the feasibility of combining systemic therapy with surgery for advanced intrahepatic cholangiocarcinoma (ICC). However, the absence of consensus on oncological resectability criteria has hindered discussions on optimal multidisciplinary management. This study sought to propose preoperative oncological resectability criteria for ICC. METHODS: Patients undergoing upfront curative-intent hepatectomy for ICC were identified from an international multi-institutional database. Independent tumor-related prognostic factors for overall survival were identified by using multivariable Cox regression and utilized to develop resectability criteria. RESULTS: Among 953 patients, four independent tumor-related predictors of poor prognosis were identified: lymph node metastasis (LNM) on imaging (HR 1.3, 95% confidence interval [CI] 1.07-1.59), tumor size > 5 cm (hazard ratio [HR] 1.52, 95% CI 1.25-1.85), multinodular lesions (HR 2.03, 95% CI 1.64-2.52), and major vascular invasion (HR 1.64, 95% CI 1.34-2.01). High-risk points were identified based on a point system associated with the hazards of each factor: 1 point each for LNM, tumor size > 5 cm, and major vascular invasion, and 2 points for multinodular lesions. Patients were categorized as resectable (R) for scores of 0-1 or borderline resectable (BR) for scores ≥ 2. Patients with BR disease (n = 385, 40.4%) had markedly worse median overall survival versus individuals with R disease (n = 568, 59.6%) (24.6 months vs. 69.7 months, p < 0.001). Validation in an external cohort confirmed these findings. CONCLUSIONS: The proposed preoperatively assessable resectability criteria can help differentiate BR versus R disease among ICC patients. These criteria offer a practical framework for preoperative risk stratification, aiding in treatment planning.