Comparative analysis of immunochemotherapy with versus without radiation therapy for stage IVB esophageal squamous cell carcinoma confined to non-regional nodal metastases: a multicenter propensity score matching study.

BACKGROUND: The survival benefit of adding radiotherapy (RT) to immunochemotherapy (ICT) in patients with stage IVB esophageal squamous cell carcinoma (ESCC) confined to non-regional lymph node metastases remains uncertain. This study evaluated whether RT combined with first-line PD-1 inhibitor-based ICT improves outcomes. METHODS: In this multicenter retrospective cohort study, 343 patients with stage IVB ESCC (non-regional nodal metastases only; AJCC 8th edition) treated with PD-1 inhibitors plus chemotherapy between 2019 and 2021 were analyzed. Patients were stratified into RT (ICT + RT, n = 181) and non-RT (ICT alone, n = 162) groups. Propensity score matching (PSM) balanced baseline characteristics (age, sex, metastatic sites, etc.), yielding 125 matched pairs. RT (> 40 Gy to primary lesions) was delivered via IMRT/VMAT (median dose, 50.4 Gy). Primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: After PSM, the RT group showed significantly longer median OS (22.3 vs 14.9 months; HR 0.51, 95% CI 0.37-0.71; P < 0.001) and PFS (14.0 vs 6.1 months; HR 0.57, 95% CI 0.42-0.77; P < 0.001) versus non-RT. Sequential RT (post-induction ICT) conferred maximal OS benefit (median OS 29.2 vs 12.1 months; HR 0.38, P < 0.001). Exploratory analysis indicated that the most significant survival benefit was observed in patients receiving sequential RT targeting the primary tumor with or without metastatic nodes, rather than metastasis-directed RT alone. Grade 3-5 treatment-related adverse events were comparable between groups; however, RT was associated with significantly higher rates of grade 3-4 lymphopenia (15.2% vs 4.0%, p = 0.004) and esophagitis (11.2% vs 0%, p < 0.001). CONCLUSION: Adding RT to first-line ICT improves survival in stage IVB ESCC with non-regional nodal metastases, particularly when delivered sequentially to the primary tumor.