Radiotherapy as an organ-preserving alternative to surgery in patients with locally advanced esophageal squamous cell carcinoma achieving major pathologic response after induction immunochemotherapy.

With the advancement of immunotherapy, neoadjuvant immunochemotherapy has emerged as an effective approach for treating locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, whether radiotherapy can serve as a reliable organ-preserving alternative following induction immunochemotherapy (IICT), and which patient subgroups benefit most, remains uncertain. In this retrospective study, 388 patients with LA-ESCC were analyzed, including 299 who underwent surgery and 89 who received radiotherapy after IICT. Responses to immunochemotherapy were classified as major pathologic response (MPR) or non-MPR based on pathologic examination for surgical patients and a previously developed MPR predictive model for radiotherapy patients. Survival outcomes were assessed using the Kaplan-Meier method, while prognostic factors were evaluated through Cox regression analyses. Propensity score matching (PSM) was used to minimize confounding factors. Surgery was associated with better progression-free survival (PFS) compared to radiotherapy (p = 0.002 before PSM; p = 0.017 after PSM), but no significant difference in overall survival (OS) was observed (p = 0.144 before PSM; p = 0.241 after PSM). Among MPR patients, radiotherapy achieved PFS and OS outcomes similar to surgery (PFS: p = 0.136; OS: p = 0.255) after PSM. Failure patterns differed, with local or regional recurrence being more common in the radiotherapy group, while distant metastasis was prevalent in surgery patients. Major postoperative complications occurred in 9.36% of surgery patients, and 11.2% of radiotherapy patients had grade 3-4 adverse events. These findings indicate that radiotherapy could be a safe and effective organ-preserving alternative for LA-ESCC patients, especially those achieving MPR, offering more personalized and less invasive treatment options while maintaining quality of life.