Comparison of Efficacy and Safety of Combined Chemoimmunotherapy With or Without Radiation Therapy for Stage IVB Esophageal Squamous Cell Carcinoma: A Multicenter Propensity Score Matching Analysis

Abstract

PurposeThis study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiotherapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). MethodsWe retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiotherapy of ≥ 40 Gy radiation dose to primary lesion, from four academic cancer centers between October 2018 and December 2022. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. ResultsIn the overall cohort of 409 patients, the group that received additional radiotherapy had superior overall survival (OS) (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.39-0.66, P < 0.001) and progression-free survival (PFS) (HR: 0.52, 95% CI: 0.40-0.66, P < 0.001) compared to the group that received chemoimmunotherapy alone. After 1:1 PSM, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiotherapy significantly improved OS and PFS (median OS: 24.9 vs. 14.6 months, P = 0.003; median PFS: 14.2 vs. 10.6 months, P = 0.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiotherapy was an independent prognostic factor for both OS (HR: 0.57, 95% CI: 0.41-0.81) and PFS (HR: 0.63, 95% CI: 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with non-regional lymph node metastases only who received radiotherapy (HR: 0.49, 95% CI: 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR: 0.72, 95% CI: 0.46-1.13). Regarding safety, the group receiving additional radiotherapy had higher incidences of grade 3-4 lymphopenia (74.4% vs. 17.7%, P < 0.001) and esophagitis (11.2% vs. 2.4%, P = 0.006). ConclusionThe addition of radiotherapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with non-regional lymph nodes metastasis.