Kawashima Jun, Endo Yutaka, Woldesenbet Selamawit, Khalil Mujtaba, Akabane Miho, Cauchy François, Shen Feng, Maithel Shishir, Popescu Irinel, Kitago Minoru, Weiss Matthew J, Martel Guillaume, Pulitano Carlo, Aldrighetti Luca, Poultsides George, Ruzzente Andrea, Bauer Todd W, Gleisner Ana, Marques Hugo, Koerkamp Bas Groot, Endo Itaru, Pawlik Timothy M
Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
Ann Surg Oncol. 2025 Mar 21. doi: 10.1245/s10434-025-17156-5.
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.
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.
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.
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.
无复发生存期（RFS）作为肝内胆管癌（ICC）患者接受初次手术时总生存期（OS）的有效替代终点的作用尚未明确。我们试图评估ICC手术切除后RFS与OS之间的相关性。我们假设RFS是ICC患者OS的可靠替代终点。
从一个国际多机构数据库中确定2000年至2023年间接受ICC初次根治性手术的患者。使用秩相关评估RFS与OS之间的相关性。地标分析评估术后5年生存率与术后6、12、24、36、48和54个月复发状态之间的一致性。
在1541例接受根治性肝切除的患者中，中位RFS和OS分别为22.6个月和41.5个月。确定RFS与OS之间存在中度强相关性（ρ = 0.79，95%CI 0.76至0.82）。在地标分析中，术后5年OS与不同时间点（6、12、24、36、48和54个月）复发状态之间的一致性分别为60.7%、72.0%、81.4%、83.1%、83.0%和82.5%。受限立方样条分析表明，基于RFS对OS的预测随时间增加，并在术后3年达到平稳。
在接受ICC根治性切除的患者中，RFS与OS之间存在中度强相关性。3年RFS可能是预测5年OS的可靠替代终点，应在未来的试验设计中予以考虑。
