Early Recurrence Patterns After Neoadjuvant Chemoradiotherapy and Chemoimmunotherapy in Oesophageal Squamous Cell Carcinoma: A Multicentre Study

The goal of this study was to compare early recurrence patterns and survival outcomes between neoadjuvant chemoimmunotherapy (NCIT) and neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced oesophageal squamous cell carcinoma.

This retrospective cohort study included 1428 patients with stage IIB-IVA esophageal squamous cell carcinoma who underwent NCIT or NCRT followed by a radical surgical procedure. Outcomes included overall survival (OS), recurrence-free survival, loco-regional recurrence, distant metastasis, and post-recurrence survival. Propensity score matching (1:1 ratio, 0.1 caliper; balance threshold: standardized mean difference <0.10) and multivariable Cox regression were utilized.

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 recurrence-free survival (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, post-recurrence survival did not differ between the 2 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 a major pathological response (HR, 0.61; 95% CI, 0.47-0.84; P < .001).

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 post-operative surveillance in high-risk patients.