Radiotherapy with versus without concurrent immunotherapy following neoadjuvant chemoimmunotherapy in unresectable locally advanced esophageal squamous cell carcinoma

PURPOSE: To evaluate the impact on survival outcomes of adding concurrent immunotherapy to radiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma following neoadjuvant chemoimmunotherapy. MATERIALS AND METHODS: We included patients with stage II–IVA ESCC treated between January 2013 and May 2024. Survival was compared between the radiotherapy without concurrent immunotherapy and radiotherapy with concurrent immunotherapy groups. RESULTS: Of the 91 enrolled patients, 35 received radiotherapy without concurrent immunotherapy and 56 received radiotherapy with concurrent immunotherapy. Median overall survival was worse in the radiotherapy without concurrent immunotherapy group compared to the radiotherapy with concurrent immunotherapy group (18 vs. 41 months; hazard ratio = 0.39, 95% confidence interval: 0.18–0.82; P = 0.013). In contrast, no differences were observed in median disease-free survival, locoregional recurrence-free survival, or distant metastasis-free survival between the two groups. Grade ≥ 3 leukopenia and neutropenia occurred more frequently in the concurrent immunotherapy group. CONCLUSION: In this real-world cohort, concurrent immunotherapy was associated with improved overall survival in patients with unresectable locally advanced esophageal squamous cell carcinoma who received prior neoadjuvant chemoimmunotherapy. These findings are hypothesis-generating and highlight the need for prospective randomized trials to validate the optimal integration of immunotherapy in this multimodal treatment sequence.