Early recurrence patterns after neoadjuvant chemoradiotherapy and chemoimmunotherapy in esophageal squamous cell carcinoma: A multicenter study

OBJECTIVE: To compare early recurrence patterns and survival outcomes between neoadjuvant chemoimmunotherapy (NCIT) and neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective cohort study included 1428 patients with stage IIB-IVA ESCC who underwent NCIT or NCRT followed by radical surgery. Outcomes included overall survival (OS), recurrence-free survival (RFS), locoregional recurrence, distant metastasis, and post-recurrence survival (PRS). Propensity score matching (1:1 ratio, 0.1 caliper; balance threshold: standardized mean difference <0.10) and multivariable Cox regression were utilized. RESULTS: After propensity score matching (532 patients per group), the NCIT group exhibited better 3-year OS (72.2% vs 60.9%; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.56-0.85; P < .001) and RFS (67.8% vs. 59.3%; HR, 0.70; 95% CI, 0.57-0.86; P < .001) than the NCRT group. The NCIT group also had lower rates of early overall recurrence (131 [24.6%] vs. 196 [36.8%]; P < .001) and early distant metastasis (73 [13.7%] vs. 125 [23.5%]; P < .001) than the NCRT group. Multivariable regression analysis identified NCRT (vs NCIT), higher ypN stage, and not achieving a major pathological response as independent risk factors for both early overall recurrence and early distant metastasis. Among patients who experienced early recurrence, PRS did not differ between the two modalities (HR, 0.81; 95% CI, 0.63-1.04; P = .086). Although the NCRT group had a higher major pathological response rate, NCIT was associated with better early recurrence control even among patients achieving major pathological response (HR, 0.61; 95% CI, 0.47-0.84; P < .001). CONCLUSIONS: Compared with NCRT, NCIT is associated with a lower incidence of early recurrence, particularly distant metastasis, which may contribute to the observed OS advantage. The poor prognosis after early recurrence highlights the need for intensified postoperative surveillance in high-risk patients.