Comparison of efficacy and safety of neoadjuvant regimens for resectable esophageal squamous cell carcinoma: A meta-analysis.

person Ting Wang The First Hospital of Guangdong Pharmaceutical University, Guangzhou, China info_outline Ting Wang, Liyu Cai, Zefeng Guo, Peimeng You, Shengbo Liu, Hongrui Qiu, Hao Li, Shaowei Wu, HaiYu Zhou

Authors person Ting Wang The First Hospital of Guangdong Pharmaceutical University, Guangzhou, China info_outline Ting Wang, Liyu Cai, Zefeng Guo, Peimeng You, Shengbo Liu, Hongrui Qiu, Hao Li, Shaowei Wu, HaiYu Zhou Organizations The First Hospital of Guangdong Pharmaceutical University, Guangzhou, China, Department of Radiation Oncology, Cancer Hospital of Nanchang University, Jiangxi Key Laboratory of Translational Cancer Research (Jiangxi Cancer Hospital of Nanchang University), Nanchang, China, Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong, China, Guangzhou University of Chinese Medicine, Guangzhou, China, DepartmentofThoracicSurgery,GuangdongProvincialPeople'sHospital, Guangzhou, China, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China, Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China Abstract Disclosures Research Funding No funding received None. Background: Recent studies have demonstrated that preoperative neoadjuvant therapy in esophageal carcinoma can bring extra survival benefits compared to surgical resection alone or postoperative adjuvant therapy. There is still a lack of high-level evidence from large randomized controlled clinical trials to define the interval between neoadjuvant therapy and surgery, radiotherapy dose and target area plans after neoadjuvant treatment, therefore we adopted a meta-analysis to compare the efficacy and safety of different neoadjuvant treatment options in esophageal squamous cell carcinoma (ESCC) in these clinical studies. Methods: Articles were retrieved from PubMed, Cochrane, Embase, Web of Science databases and abstracts of ASCO and ESMO meetings in 2021-2022 by the terms esophageal cancer, neoadjuvant therapy, Inclusion criteria: a: Patients with excisable stage esophageal cancer. Histopathological confirmed squamous carcinoma of the esophagus; b: At least one reported primary outcome as follows: pathological complete response (pCR) rate; major pathological response (MPR) rate. Statistical analysis was performed on Stata 16.0 and R 4.0 with a significance level of 0.05. Results: A total of 39 clinical studies with a total of 2,434 patients, mostly male, were included, with a predominance of phase 2 trials. 16 neoadjuvant chemotherapy combined with immunotherapy (nICT), 2 neoadjuvant immunotherapy alone, 5 neoadjuvant chemoradiotherapy combined with immunotherapy (nICRT), 15 neoadjuvant chemoradiotherapy (nCRT), 1 neoadjuvant chemotherapy, 32 single-arm studies, and 7 randomized controlled trials. The overall neoadjuvant therapy pCR rate was 36% (95% CI: 32%-40%) and the overall MPR rate was 55% (95% CI: 47%-63%). The nICT pathological complete response rate was 31% (95% CI: 26%-36%), nCRT pathological complete response rate was 38% (95% CI: 32%-44%) and nICRT complete pathological response rate was 49% (95% CI: 39% -59%). Complete pathological response rates were 36% (95% CI: 31%-41%) for neoadjuvant immunotherapy (with immunotherapy) and 33% (95% CI: 13%-54%) for neoadjuvant immunotherapy alone. 26 studies had a mean R0 resection rate of 93%, with the majority of patients achieving R0 resection. Conclusions: From this Meta-analysis it can be concluded that nICRT has the best complete pathological response rate of all neoadjuvant treatments and nCRT has a better complete pathological reponse rate than nICT, but most of them are not phase 3 clinical trials, therefore more studies are needed to further clarify the benefit of neoadjuvant radiotherapy combined with immunotherapy in esophageal squamous cell carcinoma.