Recurrence-free survival as a putative surrogate for overall survival in phase III trials of curative-intent treatment of colorectal liver metastases: Systematic review.

AIM: To verify whether recurrence-free survival (RFS) surrogates overall survival (OS) in phase III trials for resectable colorectal liver metastases (CRLM). METHODS: MEDLINE, EMBASE, and Scopus databases were consulted. Eligible studies were phase III trials testing any type of systemic therapy (neoadjuvant, adjuvant or perioperative) added to surgery in patients with resectable CRLM. A linear regression model based on hazard ratios (HR) of OS and RFS was performed. RESULTS: Of 3059 studies, 5 phase III trials (1162 patients) were included for analyses. A linear regression weighted by each trial was used to estimate the association between each HR and RFS. The originated formula was: OS HR = (0.93 × RFS HR) + 0.14; with RFS 95%CI (0.48-1.38), with P = 0.007. CONCLUSION: This association suggests that RFS could work as a putative surrogate endpoint of OS in this population, avoiding bigger, longer and more resource-consuming trials. The OS could be assumed based on RFS and our model could be useful to better estimate sample size calculations of phase III trials of CRLM aiming for OS.