Early recurrence prediction after curative-intent surgery of intrahepatic cholangiocarcinoma using a novel weighted tumor burden score

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BACKGROUND: Recurrence after curative-intent resection of patients with intrahepatic cholangiocarcinoma (ICC) remains common and difficult to predict. Tumor burden scores (TBS) incorporating tumor size and tumor nodule number have been proposed, but the relative contribution of multifocality remains unclear. METHODS: Patients undergoing curative-intent surgery for ICC in a large hepatobiliary center between 2009 and 2024 were retrospectively analyzed. A simplified weighted tumor burden score (wTBS) was developed using tumor size and tumor nodule number (wTBS = largest tumor diameter (cm) + 5 × tumor nodule number). The score was derived in a primary cohort and externally validated in an independent cohort. Early recurrence was defined as recurrence within 12 months after surgery. Predictive performance was assessed using logistic regression analysis, receiver operating characteristic (ROC) analysis, Kaplan-Meier survival curve analysis and Cox regression models. RESULTS: A total of 198 patients were included in this study. In the study cohort, the wTBS was significantly associated with early recurrence (OR 1.12 per point, 95% CI 1.07-1.18, p < 0.001) and recurrence-free survival (RFS; HR 1.06 per point, 95% CI 1.04-1.09, p < 0.001). ROC analysis demonstrated improved discriminatory performance compared to tumor size or tumor nodule number alone (area under the curve [AUC] 0.69). Using a cutoff of ≥ 14, patients with high wTBS had significantly shorter RFS (median 9 vs. 21 months, p < 0.001). These findings were confirmed in an independent validation cohort comprising 162 patients, in which wTBS remained significantly associated with early recurrence (OR 1.12) and RFS (HR 1.08, p < 0.001) with a median RFS of 7 vs. 26 months for high- vs. low-risk patients. CONCLUSIONS: A simplified wTBS incorporating tumor size and tumor nodule number was associated with early recurrence after ICC resection and showed consistent prognostic value in an independent cohort. Given its moderate discriminatory ability, the score should currently be regarded as an adjunct for postoperative risk stratification rather than a stand-alone tool for treatment selection. Prospective validation and evaluation of clinical utility are required before implementation in treatment algorithms.