Junhui Wang, Jianxin Chen
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.
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.