Concurrent Chemoradiotherapy with or without Induction Chemoimmunotherapy in Unresectable Esophageal Squamous Cell Carcinoma: A Multicenter Real-World Study

Purpose: This study aimed to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) with or without induction chemoimmunotherapy (CI) in unresectable esophageal squamous cell carcinoma (ESCC). Materials and Methods: The study included patients with unresectable ESCC who received CCRT with or without induction CI at three cancer centers. Patients receiving concurrent immunotherapy were excluded. Propensity score matching (PSM) balanced baseline characteristics between groups. Results: A total of 519 patients were included. After PSM, 183 patients per group were selected. Induction CI significantly improved OS and PFS compared to CCRT alone, consistently. The median OS for CCRT and induction CI groups were 29.9 months (95% CI: 18.8-41.0) and not reached (HR: 0.57, 95% CI: 0.42-0.77, p < 0.001). The median PFS was 17.6 months (IQR: 13.7-21.4) versus 30.6 months (IQR: 17.3-43.8) (HR: 0.66, 95% CI: 0.51-0.86, p = 0.002). Responders to the induction CI had significantly better OS (HR: 0.22, 95%CI: 0.14-0.36, p < 0.001) than nonresponders. Subgroup analysis showed radiation dose escalation or consolidation immunotherapy did not further improve survival in the induction CI group. Conclusion: The addition of induction chemoimmunotherapy to CCRT was associated with improved survival in patients with locally advanced unresectable ESCC, particularly in responders to induction chemoimmunotherapy, with acceptable toxicity. These findings warrant confirmation in prospective randomized trials.