Neoadjuvant Chemoimmunotherapy versus Chemoradiotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Systematic Review and Reconstructed Individual Patient Data Meta-Analysis
In brief
Chemoimmunotherapy linked to 12-point higher 3-year survival in esophageal cancer
Across 34 prospective studies, 3-year survival was 74.7% with neoadjuvant chemoimmunotherapy and 63.2% with chemoradiotherapy; progression-free survival was also higher, while complete and major tumor responses were less frequent. Because this was a meta-analysis of separate studies rather than a randomized head-to-head trial, long-term randomized studies are needed to confirm the survival advantage.
- Journal
- Annals of surgical oncology (Q1)
- Published
- 23 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Yaocan Xu, Yingyun Liang, Weiwei Gao, Xiaomin Yang, Fengfei Qin, Zheng Tao, et al.
- PMID
- 42778840
- DOI
- 10.1245/s10434-026-20281-4
Why clinicians should know about it
- Picked for Gastrointestinal and Colorectal Surgery (paper of the day, 26 September 2026): Neoadjuvant chemoimmunotherapy improves survival vs chemoradiotherapy in ESCC
- Picked for Surgical Oncology (paper of the day, 26 September 2026): NCIT vs NCRT impacts esophageal cancer surgery
Abstract
BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) plus surgery is standard for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC), but survival remains suboptimal. Neoadjuvant chemoimmunotherapy (NCIT) is an emerging alternative. This meta-analysis compared efficacy, safety, and survival between NCIT and NCRT. MATERIALS AND METHODS: Prospective trials on NCIT or NCRT for resectable LA-ESCC were searched up to 17 March 2026. Pathological complete response (pCR), major pathological response (MPR), overall survival (OS), and progression-free survival (PFS) were assessed. Survival data were reconstructed from Kaplan-Meier curves, and one-stage meta-analysis using shared-frailty Cox models was performed. RESULTS: A total of 34 studies (1275 NCIT, 1045 NCRT patients) were included. NCIT significantly improved OS (HR 0.63, 95% CI 0.47-0.84) and PFS (HR 0.69, 95% CI 0.51-0.93). The 3-year OS rates were 74.7% (NCIT) versus 63.2% (NCRT); 3-year PFS rates were 65.7% versus 54.6%. Adjuvant immunotherapy further improved survival (OS HR 0.51, 95% CI 0.32-0.83). pCR (31% versus 39%) and MPR (55% versus 64%) were lower with NCIT (P < 0.05). Among NCIT patients, MPR predicted better OS (HR 0.27, 95% CI 0.13-0.57). Neoadjuvant treatment with 3-4 cycles was associated with a significantly higher pCR rate compared with 2 neoadjuvant cycles (41% versus 26%, P < 0.001). Among studies using two neoadjuvant cycles, the nab-paclitaxel backbone improved pCR (32% versus 19%) and MPR (59% versus 34%) compared with paclitaxel. Postoperative anastomotic leakage was lower with NCIT (7% versus 12%), while pneumonia and 90-day mortality were comparable. CONCLUSIONS: NCIT provides superior survival and a manageable safety profile compared with NCRT in resectable LA-ESCC. Neodjuvant immunotherapy extending to 3-4 cycles and adding adjuvant immunotherapy may enhance outcomes. Long-term RCTs 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.