Recurrence-Free Survival as a Surrogate for Overall Survival Among Patients with Intrahepatic Cholangiocarcinoma Following Upfront Surgery: An International Multi-institutional Analysis

Introduction: The role of recurrence-free survival (RFS) as a validated surrogate endpoint for overall survival (OS) among patients undergoing upfront surgery for intrahepatic cholangiocarcinoma (ICC) has not been defined. We sought to evaluate the correlation between RFS and OS after surgical resection for ICC. We hypothesized that RFS was a reliable surrogate endpoint for OS among patients with ICC. Methods: Patients who underwent upfront curative-intent surgery for ICC between 2000 and 2023 were identified from an international, multi-institutional database. The correlation between RFS and OS was assessed using rank correlation. Landmark analysis evaluated concordance between survival at 5 years and recurrence status at 6, 12, 24, 36, 48, and 54 months postoperatively. Results: Among 1541 patients who underwent curative-intent hepatic resection, the median RFS and OS were 22.6 months and 41.5 months, respectively. A moderately strong correlation between RFS and OS was identified (ρ = 0.79, 95% CI 0.76 to 0.82). In the landmark analysis, the concordance between 5-year OS after surgery and recurrence status at different time points (6, 12, 24, 36, 48, and 54 months) was 60.7%, 72.0%, 81.4%, 83.1%, 83.0%, and 82.5%, respectively. Restricted cubic spline analysis indicated that the prediction of OS based on RFS increased with time and plateaued 3 years after surgery. Conclusions: Among patients undergoing curative-intent resection of ICC, there was a moderately strong correlation between RFS and OS. Three-year RFS may be a reliable surrogate endpoint to predict 5-year OS and should be considered in future trial design.