P1.082. Neoadjuvant Chemoradiotherapy-to-Surgery Interval and Survival Stratified by Pathological Response in Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter Study

Abstract

Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal interval between nCRT completion and surgery remains undetermined, particularly regarding its differential impact based on pathological response status. This study aimed to evaluate the association between the nCRT-to-surgery interval and survival outcomes in patients with and without pathological complete response (pCR). A retrospective multicenter cohort study was conducted including 484 patients with locally advanced ESCC who received nCRT followed by minimally invasive esophagectomy across three centers between 2010 and 2019. Patients were categorized into short-interval (≤50 days) and long-interval (>50 days) groups. Overall survival (OS) and disease-free survival (DFS) were compared in the overall population and stratified by pCR status. Multivariate Cox proportional hazards regression was performed to identify independent prognostic factors. Among 484 patients, 64 (21.1%) were in the short-interval group and 239 (78.9%) in the long-interval group, with comparable pCR rates (34.7% vs. 36.7%). The short-interval group demonstrated significantly higher five-year OS (64.9% vs. 49.0%, P=0.039), while DFS showed a trend toward significance (62.2% vs. 48.1%, P=0.054). Multivariate Cox analysis identified poor differentiation (HR 2.936, 95% CI 1.292–6.675), ypN2 (HR 2.321, 95% CI 1.195–4.508), lymphovascular invasion (HR 2.238, 95% CI 1.167–4.291), and interval >50 days (HR 2.570, 95% CI 1.317–5.017) as independent risk factors for OS. In the non-pCR subgroup, five-year OS (66.9% vs. 45.7%, P=0.008) and DFS (56.7% vs. 40.5%, P=0.009) were significantly better in the short-interval group, whereas no significant survival differences were observed in the pCR subgroup. Short-term mortality rates were comparable between groups. A prolonged nCRT-to-surgery interval was independently associated with worse survival in patients with locally advanced ESCC, particularly among non-pCR patients. In the pCR subgroup, the interval did not significantly affect survival outcomes. These findings suggest that pathological response status may modulate the impact of surgical timing on prognosis, providing preliminary real-world evidence that warrants prospective investigation into organ preservation strategies for carefully selected pCR patients.