Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma

BackgroundRecurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common.ObjectiveThe aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC.MethodsPatients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed.ResultsA total of 920 patients were included. With a median follow-up of 38months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0m) and extrahepatic-only recurrence (median 8.0m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0m; p<0.05). On multivariate analysis, surgical margin<10mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p=0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p<0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p=0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7months) versus other treatments (9.7months) [p<0.001].ConclusionsDifferent recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.