Concurrent versus sequential immune checkpoint inhibition in the neoadjuvant treatment of resectable esophageal squamous cell carcinoma: a systematic review and meta-analysis
In brief
With chemoradiotherapy, complete response was 48% vs 41% by immunotherapy timing
Across 53 prospective studies involving 2,937 patients, sequential immunotherapy initially appeared to yield more complete tumor responses than concurrent treatment: 48% versus 31%. But among studies using chemoradiotherapy in both groups, rates were 48% versus 41%, a difference that was not statistically significant. The comparison suggests treatment backbone, not timing, may explain the apparent advantage; randomized trials are needed.
- Journal
- Clinical and translational radiation oncology (Q1)
- Published
- 10 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Reza Ghalehtaki, Alireza Shariati, Taher Fanihagh, Zahra Moradi, Niloofar Moradi
- PMID
- 42787301
- DOI
- 10.1016/j.ctro.2026.101289
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 27 September 2026): Immune checkpoint timing in esophageal cancer, oncology focus
- Picked for Pathology and Forensic Medicine (top studies of the week, 27 September 2026): High-quality evidence in a top journal
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.