The efficacy of time interval between neoadjuvant chemoimmunotherapy and surgery on outcomes in esophageal squamous cell carcinoma

Abstract Objectives While neoadjuvant immunotherapy combined with chemotherapy (NICT) has demonstrated promising efficacy in esophageal squamous cell carcinoma (ESCC), the optimal interval between NICT and surgery remains undefined. This study aims to investigate the impact of this interval on pathological response and survival in ESCC patients. Methods Totally of 254 patients with locally advanced ESCC who underwent surgical resection following NICT between September 2020 and January 2024 were retrospectively analyzed. Based on the time interval from NICT completion to surgery (TTS), patients were stratified into two cohorts: within 8 weeks and exceeding 8 weeks. The association between the TTS and postoperative outcomes and long-term prognosis were evaluated. Results A total of 254 patients were included in the study, 124 patients underwent surgery within 8 weeks after NICT, while 130 patients had surgery over 8 weeks. Among the patients who underwent surgery over 8 weeks, 31 patients (23.8%) achieved pathological complete response (pCR), and 14 patients (11.3%) who underwent surgery within 8 weeks achieved pCR (P = 0.009). Long-term survival analysis demonstrated that patients underwent surgery over 8 weeks had significantly better overall survival (OS) (HR: 0.433, 95% CI: 0.233-0.806, P = 0.008) and disease-free survival (DFS) (HR: 0.451, 95% CI: 0.272-0.748, P = 0.002) compared to those who had surgery within 8 weeks. Conclusions A prolonged surgical interval exceeding 8 weeks following NICT is significantly associated with an increased rate of pCR. Furthermore, delayed surgical intervention beyond the 8-week threshold demonstrates a potential survival benefit in patients with locally advanced ESCC.