Real-World Effectiveness of Anti–PD-1 Immunotherapy Combined with Definitive Chemoradiotherapy in Inoperable ESCC: A Multicenter Weighted Analysis

The unclear benefit of supplementing definitive chemoradiotherapy (dCRT) with immune checkpoint inhibitors (ICIs) for unresectable esophageal squamous cell carcinoma (ESCC) warrants investigation into whether the timing of immunotherapy during the peri-dCRT window shapes survival. Patients with non-resectable ESCC who received dCRT plus ICIs between April 2018 and April 2022 were enrolled at five Chinese hospitals. A historical reference arm receiving dCRT only was used for benchmarking. Stabilized inverse probability of treatment weights (sIPTW) techniques were applied to contrast survival endpoints. Both efficacy metrics and treatment-emergent toxicities were appraised. The study cohort included 290 patients with inoperable ESCC managed with dCRT+ICI. Over a median observation period of 35.7 months, 1- and 2-year overall survival (OS) figures were 86.7% and 66.9%, respectively, whereas 1- and 2-year progression-free survival (PFS) were 66.7% and 47.3%, respectively. Median PFS was recorded at 22.4 months; median OS remained undefined. The dCRT+ICI arm demonstrated meaningfully longer OS than the historical comparator (2-year OS: 66.9% versus 56.5%; sIPTW-weighted analysis: HR = 0.62, P < .001). After sIPTW adjustment, OS did not diverge among the induction, concurrent, and consolidation cohorts. The sIPTW-weighted evaluation revealed that both the induction and concurrent cohorts achieved significantly longer PFS than the consolidation cohort. Combining immunotherapy with dCRT improved survival and maintained a tolerable toxicity profile in inoperable ESCC. Deploying immunotherapy during induction or concurrent phases may yield a greater survival benefit than consolidation-phase administration.