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

BackgroundEsophageal 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 th...

Full description

Saved in:
Bibliographic Details
Main Authors: Tao Luo, Hao Yang, Xingqiang Ran, Binwen Xu, Yue Zhang, Liwen Zhang, Chengcheng Zhang, Maoyong Fu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1590111/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849762566703677440
author Tao Luo
Hao Yang
Xingqiang Ran
Binwen Xu
Yue Zhang
Liwen Zhang
Chengcheng Zhang
Maoyong Fu
author_facet Tao Luo
Hao Yang
Xingqiang Ran
Binwen Xu
Yue Zhang
Liwen Zhang
Chengcheng Zhang
Maoyong Fu
author_sort Tao Luo
collection DOAJ
description BackgroundEsophageal 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.MethodsA 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.ResultsThe final analysis incorporated four randomized controlled trials (RCTs) comprising a total cohort of 629 participants. Patients receiving nICT for locoregionally advanced esophageal carcinoma demonstrated significantly prolonged intervals between final preoperative treatment and definitive surgical resection when compared to those undergoing conventional 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).ConclusionNeoadjuvant 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.
format Article
id doaj-art-9a11d5063a404806be7e3cfcbd6b29dc
institution DOAJ
issn 2234-943X
language English
publishDate 2025-08-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-9a11d5063a404806be7e3cfcbd6b29dc2025-08-20T03:05:42ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.15901111590111Analysis 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 trialsTao LuoHao YangXingqiang RanBinwen XuYue ZhangLiwen ZhangChengcheng ZhangMaoyong FuBackgroundEsophageal 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.MethodsA 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.ResultsThe final analysis incorporated four randomized controlled trials (RCTs) comprising a total cohort of 629 participants. Patients receiving nICT for locoregionally advanced esophageal carcinoma demonstrated significantly prolonged intervals between final preoperative treatment and definitive surgical resection when compared to those undergoing conventional 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).ConclusionNeoadjuvant 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1590111/fullesophageal cancerneoadjuvant chemoimmunotherapyneoadjuvant chemotherapyrandomized controlled trialsmeta-analysis
spellingShingle Tao Luo
Hao Yang
Xingqiang Ran
Binwen Xu
Yue Zhang
Liwen Zhang
Chengcheng Zhang
Maoyong Fu
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
Frontiers in Oncology
esophageal cancer
neoadjuvant chemoimmunotherapy
neoadjuvant chemotherapy
randomized controlled trials
meta-analysis
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic esophageal cancer
neoadjuvant chemoimmunotherapy
neoadjuvant chemotherapy
randomized controlled trials
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1590111/full
work_keys_str_mv AT taoluo analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials
AT haoyang analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials
AT xingqiangran analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials
AT binwenxu analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials
AT yuezhang analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials
AT liwenzhang analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials
AT chengchengzhang analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials
AT maoyongfu analysisofthesafetyandefficacyofpd1pdl1inhibitorscombinedwithchemotherapyinthetreatmentoflocallyadvancedresectableesophagealsquamouscellcarcinomaasystematicreviewandmetaanalysisbasedonfourrandomizedcontrolledtrials