Concurrent Versus Sequential Immune Checkpoint Inhibition in the Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis Publisher



Ghalehtaki R ; Shariati A ; Fanihagh T ; Moradi Z ; Moradi N
Source: Clinical and Translational Radiation Oncology Published:2027

Abstract

Background: Immune checkpoint inhibitors (ICIs) are increasingly integrated into the neoadjuvant treatment of resectable esophageal squamous cell carcinoma (ESCC), yet the optimal timing of ICI administration remains undefined. We conducted the first systematic review and meta-analysis directly comparing these two strategies. Methods: PubMed, Embase, and Scopus were searched from inception through April 2026. Prospective studies enrolling adult patients with non-metastatic resectable ESCC who received neoadjuvant ICI alongside chemotherapy or chemoradiotherapy were eligible. Pooled pathological complete response (pCR) and major pathological response (MPR) were analyzed using random-effects models. Results: Fifty-three prospective studies (2937 patients) were included. In the primary analysis, consolidation ICI was associated with significantly higher pCR than concurrent ICI (48% vs. 31%; p = 0.0005). However, when restricted to studies using chemoradiotherapy in both arms, this difference lost statistical significance (48% vs. 41%; p = 0.18), suggesting the initial advantage was largely attributable to a greater use of chemoradiotherapy in the sequential subgroup rather than ICI timing per se. A parallel pattern was observed for MPR. Conclusions: When matched for treatment backbone, concurrent and consolidation ICI timing produce comparable pathological response rates in resectable ESCC. Randomized trials with pre-specified timing arms and biomarker stratification are warranted. © 2026 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/