Induction chemoimmunotherapy versus radiotherapy alone for inoperable esophageal squamous cell carcinoma: a real-world study.

BACKGROUND: For patients with locally advanced esophageal squamous cell carcinoma (ESCC) ineligible for surgery, definitive radiotherapy (RT) is the primary curative-intent treatment, yet outcomes remain suboptimal. The benefit of adding induction immunotherapy combined with chemotherapy prior to RT in this setting is unclear. This real-world study compared survival and safety between induction chemoimmunotherapy followed by RT and RT alone.

METHODS: This single-center, retrospective cohort study enrolled 159 patients with inoperable locally advanced ESCC treated between May 2021 and December 2025. Patients were categorized into an induction treatment group (n=48) receiving PD-1 inhibitor-based chemoimmunotherapy before RT, and a no-induction (control) group (n=111) receiving RT alone. Details regarding unsystematically administered concurrent chemotherapy were not captured. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Toxicity was assessed per CTCAE v5.0.

RESULTS: Baseline characteristics were balanced. The induction group most commonly received camrelizumab (29.2%) with a taxane-based backbone. With a median follow-up, no significant survival difference was observed. Median PFS was 16.2 months (95% CI: 6.03-26.37) vs. 16.5 months (9.91-23.09) in the induction vs. control groups, respectively (P = 0.734). Median OS was 25.8 months (7.13-44.47) vs. 24.1 months (15.18-33.02), respectively (P = 0.659). Subgroup analyses showed no statistically significant treatment-subgroup interactions. Univariable analyses identified better nutritional status (NRS2002<3) as a favorable prognostic factor for both PFS and OS, and better performance status (ECOG PS 0-1) for OS. The induction group had significantly higher rates of Grade 3-4 adverse events, including neutropenia (60.4% vs. 7.2%), anemia (47.9% vs. 9.9%), thrombocytopenia (27.1% vs. 1.8%), and nausea (83.3% vs. 6.3%).

CONCLUSION: In this real-world cohort of inoperable locally advanced ESCC patients, adding induction chemoimmunotherapy before definitive radiotherapy was not associated with improved PFS or OS but led to a significantly increased burden of severe toxicities compared to RT alone. These findings do not support the routine use of this intensive sequential strategy in an unselected, often frail, inoperable population.