Division of Lower Gastrointestinal, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Japan.
Department of Biostatistics, Hyogo Medical University, Nishinomiya, Japan.
Br J Surg. 2023 Jun 12;110(7):864-869. doi: 10.1093/bjs/znad127.
The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis.
Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005-2007 and 2013-2014). RFS, OS, and survival after recurrence were estimated using the Kaplan-Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated.
A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06).
In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.
在接受结直肠肝转移初始手术的患者中，无复发生存（RFS）作为总生存（OS）的有效替代终点的作用仍不确定。本研究的目的是在全国范围内接受结直肠肝转移初始切除的患者队列中比较这两种生存测量方法。
从日本全国数据库中检索无肝外转移的结直肠肝转移患者的数据，这些患者接受了肝转移的治愈性手术。使用 Kaplan-Meier 方法估计 RFS、OS 和复发后的生存情况。使用秩相关法结合迭代多重插补来评估 RFS 和 OS 之间的相关性（ρ），以考虑到删失。作为二次分析，根据辅助化疗方案评估相关性。在敏感性分析中，计算 RFS 和 OS 之间的两两相关性。
共纳入 2385 例结直肠肝转移患者。在主要分析中，RFS 和 OS 之间存在中度强相关性（ρ=0.73，95%可信区间为 0.70 至 0.76）。无论辅助治疗方案如何，相关性的强度相似（奥沙利铂加 5-氟尿嘧啶：ρ=0.72，0.67 至 0.77；5-氟尿嘧啶单独使用：ρ=0.72，0.66 至 0.76；观察：ρ=0.74，0.69 至 0.78）。3 年 RFS 和 5 年 OS 之间的平均（s.d.）两两相关系数为 0.87（0.06）。
在接受结直肠肝转移初始手术的患者中，RFS 和 OS 之间存在中度强相关性，不受治疗方案的影响。需要进行试验水平的分析以进一步验证。
