SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1590111
Analysis of the Safety and Efficacy of PD-1/PD-L1 Inhibitors Combined with Chemotherapy in the Treatment of Locally Advanced Resectable Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis Based on Four Randomized Controlled Trials
Provisionally accepted- Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Background:Esophageal cancer is a leading type of cancer globally,Most patients diagnosed with esophageal cancer present at a locally advanced stage, for which the standard treatment paradigm involves a multimodal approach combining neoadjuvant therapy with surgical resection. However, even under this regimen, 30–40% of patients develop distant metastases postoperatively. This underscores an urgent need to refine existing therapeutic strategies and develop innovative multimodal protocols to address persistent oncological challenges in this high-risk population.In recent years, the advent of immunotherapy has expanded its application from advanced to early-stage settings, with neoadjuvant immunotherapy gaining traction in the management of locally advanced esophageal cancer. However, critical uncertainties persist regarding its preoperative use. This study aims to conduct a meta-analysis comparing the efficacy and safety of neoadjuvant chemoimmunotherapy (NICT) versus conventional neoadjuvant chemotherapy (NCT) in this patient population.Methods: A comprehensive literature retrieval strategy was implemented across PubMed (NLM), Embase (Elsevier), and the Cochrane Central Register of Controlled Trials, targeting studies published prior to December 2024 that compared novel immunochemotherapy (NICT) with conventional NCT in locoregionally advanced esophageal carcinoma. Pooled statistical analysis of the eligible randomized controlled trials (RCTs) was subsequently conducted to evaluate comparative safety and efficacy profiles.Results: The final analysis incorporated four randomized controlled trials (RCTs) comprising a total cohort of 629 participants.Patients receiving neoadjuvant immunochemotherapy (NICT) for locoregionally advanced esophageal carcinoma demonstrated significantly prolonged intervals between final preoperative treatment and definitive surgical resection when compared to those undergoing conventional neoadjuvant chemotherapy (NCT) alone. (weighted mean difference [WMD]: 0.71 weeks; 95% confidence interval [CI] 0.39–1.02; P < 0.0001). The combined treatment showed significant advantages in pathological complete response (PCR) (odds ratio [OR]: 3.44; 95% CI 1.98–5.97; P < 0.0001) and major pathological response (MPR) (OR: 2.56; 95% CI 1.23–5.30; P = 0.01). However, the incidence of anemia as an adverse reaction was higher in the combined treatment group (OR: 1.83; 95% CI 1.08–3.09; P = 0.02).Conclusion: Neoadjuvant chemotherapy combined with immunotherapy for treating locally advanced esophageal cancer is effective and safe. However, due to the absence of long-term follow-up data, additional large-scale, multicenter randomized controlled trials are required to confirm these results.
Keywords: esophageal cancer, neoadjuvant chemoimmunotherapy, Neoadjuvant chemotherapy, randomized controlled trials, Meta-analysis
Received: 08 Mar 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Luo, Ran, xu, Zhang, zhang, Zhang and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Tao Luo, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
Maoyong Fu, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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