Chemoradiotherapy with versus without concurrent immune checkpoint inhibitor for locally advanced esophageal squamous cell carcinoma: a multicenter retrospective study

Summary To compare survival outcomes and safety between concurrent chemoradiotherapy (CCRT) and CCRT with concurrent immune checkpoint inhibitor (ICI) in patients with locally advanced esophageal squamous cell carcinoma. This multicenter cohort study enrolled consecutive patients treated between January 2010 and April 2024. Patients were stratified into two groups: CCRT and CCRT+ICI. Of 290 eligible patients, 64 received CCRT+ICI and 226 received CCRT. CCRT followed by ICI maintenance therapy improved disease-free survival compared to CCRT+ICI (hazard ratio HR = 2.33, 95% CI: 1.04-5.24; P = 0.040), although it did not improve overall survival (HR = 1.12, 95% CI: 0.45-2.81; P = 0.804). Disease-free survival (HR = 1.25, 95% CI: 0.72-2.16; P = 0.428) and overall survival (HR = 0.94, 95% CI: 0.46-1.93; P = 0.861) were comparable between CCRT alone and CCRT+ICI groups. CCRT+ICI had a higher incidence of grade ≥ 3 leukopenia and neutropenia. Following CCRT, median lymphocyte counts decreased in both CCRT+ICI (1.30 versus 0.35) and CCRT (1.57 versus 0.30) groups. In contrast, monocyte counts increased in the CCRT+ICI group (0.33 versus 0.49), but remained stable in the CCRT group (0.50 versus 0.49). CCRT with concurrent ICI failed to improve survival in patients with locally advanced esophageal squamous cell carcinoma, potentially due to CCRT induced immunosuppression. In contrast, CCRT followed by ICI maintenance therapy showed promise in improving disease-free survival, suggesting that the timing of immunotherapy integration is critical for therapeutic efficacy.