Induction Chemoimmunotherapy Versus Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Study

Background/Objectives: Induction chemotherapy offers limited survival benefit before definitive concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma. We compared induction chemoimmunotherapy followed by concurrent chemoradiotherapy (IOC-CCRT) with induction chemotherapy followed by concurrent chemoradiotherapy (IC-CCRT). Methods: This retrospective study included patients treated during 2017–2024. Propensity score matching was performed at a 2:1 ratio. Overall survival, progression-free survival, failure patterns, and treatment-related adverse events were evaluated. Results: Among 333 patients, 228 received IOC-CCRT and 105 received IC-CCRT. In the full cohort, IOC-CCRT was associated with better overall survival (p = 0.009) and progression-free survival (p = 0.005). After matching, 220 patients were included (141 IOC-CCRT and 79 IC-CCRT); IOC-CCRT remained associated with better overall survival (p = 0.0027) and progression-free survival (p = 0.0012). The 36-month overall survival rates were 59.0% versus 41.6%, and progression-free survival rates were 49.7% versus 28.0%. Overall failure occurred in 27.7% versus 39.2% of patients (p = 0.077). In multivariable analyses, the associations with progression-free survival (hazard ratio, 0.75; 95% confidence interval, 0.55–1.03; p = 0.075) and overall survival (hazard ratio, 0.82; 95% confidence interval, 0.58–1.14; p = 0.234) were not statistically significant. Grade 3 or higher neutropenia was more frequent with IOC-CCRT (31.9% versus 16.5%; p = 0.013); no grade ≥ 3 radiation pneumonitis occurred. Conclusions: IOC-CCRT was associated with improved unadjusted survival outcomes and increased selected severe toxicities compared with IC-CCRT. Prospective randomized trials are warranted.