OA01.3. Does Timing of Surgery Matter? Pathological Response and Oncological Outcomes After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Abstract

Esophageal Cancer: Surgical Treatment of Esophageal Cancer Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma The optimal interval between neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma remains controversial. Longer intervals may enhance tumor regression and complete pathological response; concerns regarding the perioperative outcomes, oncological safety, and survival persist. This study demonstrates the impact of surgical timing on pathological response and survival as the primary endpoint, with perioperative outcomes as secondary endpoints. A retrospective single-center cohort study was conducted including patients with esophageal squamous cell carcinoma who underwent esophagectomy following CROSS-based neoadjuvant chemoradiotherapy between 2013 and 2025. Patients were stratified according to the interval between completion of nCRT and surgery into three groups: ≤6 weeks, 6–8 weeks, and ≥8 weeks. The primary endpoint was pathological complete response and survival. Categorical variables were compared using the chi-square or Fisher’s exact test, and continuous variables using the independent t-test or the Mann–Whitney U test/Kruskal–Wallis test as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared with the log-rank test. A p-value < 0.05 was considered statistically significant. Across the three interval groups, pathological tumor response increased significantly from 34.8% in ≤ 6 weeks (Group A) to 47.5% in 6-8 weeks (Group B) and 62.6% in ≥ 8 weeks (Group C) (p=0.018), with a similar stepwise improvement in ypT0 (30.4% → 48.5% → 63.6%; p=0.007). Although ypN0 rates and R0 resection were comparable but not significant (p>0.60), demonstrating increased intervals improved primary tumor regression score without affecting nodal clearance or resectability rates. Postoperative outcomes, in terms of overall complications, hospital stay, etc were also similar (p>0.05), showing no increase in short-term surgical risk amongst the three groups. Long-term outcomes were statistically comparable. Group A had the lowest OS and DFS (58.8% and 42.5%), while Group B showed better 3- and 5-year OS and DFS of 79.9% and 69.7%; 71.6% respectively. Group C demonstrated the highest survival (3- and 5-year OS: 82.3% and 79.7%; DFS: 72.2%), showing a consistent improved pattern across groups. A delayed interval between nCRT and surgery was associated with significantly improved primary tumor regression and higher pCR rates and did not increase postoperative morbidity or compromise resectability. Nodal clearance and R0 resection rates remained unaffected. Although survival differences were not statistically significant, a consistent numerical improvement in OS and DFS was observed with longer intervals. These findings strongly suggest that delaying surgery beyond six weeks is oncologically safe and may enhance tumor response, with the best results in the patients in whom the surgery has been delayed by 8 weeks, indicating a potential favorable impact on long-term outcomes.