Metastatic Lymph Node Burden and Invasive Tumour Features Inform First Recurrence Patterns After Curative-Intent Resection for Intrahepatic Cholangiocarcinoma

BACKGROUND: Recurrence is a major driver of poor long-term outcomes after curative-intent resection for intrahepatic cholangiocarcinoma (iCCA), yet the association between postoperative pathology, first recurrence patterns, and post-recurrence outcomes remains unclear. METHODS: Patients who underwent curative-intent resection for iCCA (2000-2023) were identified from an international multi-institutional database. First recurrence patterns were classified as intrahepatic-only, extrahepatic-only, or combined intrahepatic and extrahepatic recurrence. Multivariable analyses assessed associations between postoperative pathologic features, first recurrence patterns, post-recurrence survival (PRS), and post-recurrence curative-intent treatment. RESULTS: Among 1,328 patients, 57.5% (n=763) recurred; 717 had a classifiable first recurrence pattern (intrahepatic-only, n=381; extrahepatic-only, n=171; combined, n=165). Three or more metastatic lymph nodes (adjusted odds ratio [aOR] 3.47, 95%CI 1.56-7.72) and microvascular invasion (aOR 2.49, 95%CI 1.61-3.85) were associated with higher odds of combined recurrence compared with intrahepatic-only recurrence, whereas perineural invasion (aOR 2.24, 95%CI 1.35-3.71) and absence of pathologic nodal evaluation (aOR 2.04, 95%CI 1.24-3.36) were associated with extrahepatic-only recurrence. Compared with intrahepatic-only recurrence, combined recurrence was associated with worse PRS (adjusted hazard ratio 1.63, 95%CI 1.29-2.06) and lower odds of receiving curative-intent treatment (aOR 0.14, 95%CI 0.06-0.29). CONCLUSIONS: Pathologic nodal burden and invasive tumour features were associated with distinct first recurrence patterns after iCCA resection. Combined recurrence, more common with three or more metastatic lymph nodes or microvascular invasion, was associated with worse PRS and lower receipt of curative-intent treatment. Among patients who develop recurrence, postoperatively available pathological prognostic factors may help characterise first recurrence patterns and inform risk-adapted postoperative surveillance.