Radiotherapy plus immunotherapy with or without chemotherapy improves survival in elderly esophageal squamous cell carcinoma: a real-world comorbidity-stratified study

Objective: This real-world study explores the efficacy and safety of radiotherapy combined with immunotherapy-based regimens in elderly patients (≥70 years) with esophageal squamous cell carcinoma (ESCC), stratified by the Cumulative Illness Rating Scale--Geriatric (CIRS-G). Given the exploratory nature and modest sample size, findings should be interpreted as hypothesis-generating. Methods: We conducted a single-center retrospective analysis of 87 elderly ESCC patients receiving intensity-modulated radiotherapy, categorized into three groups: radiotherapy alone (RT, n=49), concurrent chemoradiotherapy (CRT, n=18), and radiotherapy combined with immunotherapy ± chemotherapy (RIT ± CT, n=20). The primary endpoint was overall survival (OS). Propensity score matching (PSM) and multivariable Cox regression were performed. Results: With a median follow-up of 37 months, multivariable Cox regression analysis suggested that the RIT ± CT regimen was associated with a reduced mortality risk versus RT (HR = 0.341, 95% CI: 0.130-0.896, P = 0.029). PSM confirmed this survival advantage (OS: HR = 0.42, P = 0.028). Patients with a medium CIRS-G burden (scores 4-6) demonstrated the most significant OS benefit from this multimodal strategy. Grade ≥3 TRAEs were highest in the RIT ± CT group (55.0%), with no treatment-related deaths. Conclusion: The integration of immunotherapy-based regimens into radiotherapy shows an association with improved survival in elderly ESCC patients with a manageable safety profile. The CIRS-G score may help identify optimal candidates. These exploratory findings require validation in larger, prospective multicenter studies. The independent contribution of immunotherapy alone cannot be determined from this study.