PD01.03. Impact of Surgical Timing on Survival by Pathological Response Status in Esophageal Cancer Patients After Neoadjuvant Chemoradiotherapy

Abstract

Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is standard treatment for esophageal squamous cell carcinoma (ESCC). Optimal surgical timing after nCRT remains unclear. Patients achieving pathological complete response (pCR) may demonstrate distinct biological behavior. This study investigated whether surgical timing differentially impacts survival based on pathological response status. This multicenter retrospective study included 484 locally advanced ESCC patients (cT2N+M0 or cT3-4NanyM0) who underwent nCRT followed by minimally invasive esophagectomy (2010-2019). The nCRT regimen consisted of weekly paclitaxel/carboplatin with concurrent radiotherapy (40-41.4 Gy). Using maximally selected rank statistics, 50 days was identified as the optimal interval cutoff. Patients were stratified by interval (<50 days: n=225; >50 days: n=259) and pathological response (pCR: n=165, 34.1%; non-pCR: n=319, 65.9%). Primary outcomes were overall survival (OS) and disease-free survival (DFS). Propensity score matching controlled for confounders including age, sex, ECOG status, tumor characteristics, and treatment factors. Multivariable Cox regression identified independent prognostic factors. Among 484 patients (mean age 61.9 years, 85.1% male), mean interval was 61.0 days (short: 38.0 days; long: 67.0 days). Baseline characteristics were balanced between groups. In overall population, prolonged interval (>50 days) associated with inferior 5-year OS (49.0% vs 64.9%, P=0.039). However, subgroup analysis revealed striking differences by pathological response. In pCR patients, no significant OS difference existed between intervals. Conversely, non-pCR patients demonstrated markedly worse outcomes with prolonged intervals (66.9% vs 45.7%, P=0.008; adjusted HR=4.13, 95%CI: 1.70-10.03, P=0.002). Similar DFS patterns were observed. Findings remained consistent after propensity score matching. Multivariable analysis confirmed interval as independent prognostic factor in non-pCR but not pCR patients. Surgical timing impacts survival differently based on pathological response. Prolonged intervals significantly compromise non-pCR patient outcomes, emphasizing timely intervention importance. The absence of association in pCR patients suggests distinct tumor biology and warrants further investigation, supporting personalized surgical timing strategies.