A Surrogate Endpoint for Overall Survival in Locally Advanced and Resectable Esophageal Squamous Cell Carcinoma: A Reanalysis of Data From the NEOCRTEC5010 Trial

Purpose: This study aimed to investigate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) in patients with locally advanced and resectable esophageal squamous cell carcinoma. Methods and Materials: We re-analyzed patient data from the NEOCRTEC5010 randomized controlled trial (N = 451 patients) to compare their OS with that of an age-and sex-matched cohort from the general population of China. We used expected survival and the standardized mortality ratio, respectively, in our analysis of data collected from a neoadjuvant che-moradiation therapy (NCRT) plus surgery group and a surgery-only group. Published data from 6 randomized controlled trials and 20 retrospective studies were used to examine the correlation between DFS and OS at the trial level. Results: The annual hazard rate of disease progression decreased to 4.9% and 8.1% within 3 years in the NCRT and surgery groups, respectively. Patients who were disease-free at 36 months had a 5-year OS of 93.9% (95% CI, 89.7%-98.4%) in the NCRT group with a standardized mortality ratio of 1.1 (95% CI, 0.7-1.8; P = .5639). In contrast, the 5-year OS was only 12.9% (95% CI, 7.3%-22.6%) for patients in the NCRT group who exhibited disease progression within 36 months. At the trial level, DFS and OS were correlated with treatment effect (R2 = 0.605). Conclusions: Disease-free status at 36 months is a valid surrogate endpoint for 5-year OS in patients with locally advanced and resectable esophageal squamous cell carcinoma. Patients who were disease-free at 36 months showed a favorable OS, which was indistinguishable from that of the age-and sex-matched comparison group from the general population; otherwise, their 5-year OS was extremely poor. (c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY -NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

This study found that disease-free status at 36 months can serve as a valid surrogate endpoint for 5-year overall survival in patients with locally advanced and resectable esophageal squamous cell carcinoma. Patients who maintained disease-free status at 36 months had a favorable overall survival, while those who experienced disease progression within 36 months had a significantly poorer overall survival.