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Neoadjuvant Chemoimmunotherapy versus Chemoradiotherapy in Resectable Locally Advanced Esophageal Squamous Cell
Yaocan Xu1, Yingyun Liang2, Weiwei Gao1
1Department of Oncology, Guiping People's Hospital, Affiliated Guiping Hospital of Youjiang Medical College for Nationalities, Guiping, Guangxi Zhuang Autonomous Region, P.R. China.
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.
