Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial

H Tang; H Wang; Y Fang; J Y Zhu; J Yin; Y X Shen; Z C Zeng; D X Jiang; Y Y Hou; M Du; C H Lian; Q Zhao; H J Jiang; L Gong; Z G Li; J Liu; D Y Xie; W F Li; C Chen; B Zheng; K N Chen; L Dai; Y D Liao; K Li; H C Li; N Q Zhao; L J Tan

doi:10.1016/j.annonc.2022.10.508

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial

Ann Oncol. 2023 Feb;34(2):163-172. doi: 10.1016/j.annonc.2022.10.508. Epub 2022 Nov 15.

Authors

H Tang¹, H Wang¹, Y Fang¹, J Y Zhu², J Yin¹, Y X Shen¹, Z C Zeng², D X Jiang³, Y Y Hou³, M Du⁴, C H Lian⁵, Q Zhao⁵, H J Jiang⁶, L Gong⁷, Z G Li⁸, J Liu⁹, D Y Xie¹⁰, W F Li¹¹, C Chen¹², B Zheng¹², K N Chen¹³, L Dai¹³, Y D Liao¹⁴, K Li¹⁴, H C Li¹⁵, N Q Zhao¹⁶, L J Tan¹⁷

Affiliations

¹ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai.
² Cancer Center, Zhongshan Hospital, Fudan University, Shanghai; Department of Radiotherapy, Zhongshan Hospital, Fudan University, Shanghai.
³ Cancer Center, Zhongshan Hospital, Fudan University, Shanghai; Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai.
⁴ Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing.
⁵ Department of General Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi.
⁶ Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin.
⁷ Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin.
⁸ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.
⁹ Department of Radiotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai.
¹⁰ Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou.
¹¹ Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou.
¹² Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou.
¹³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), The First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute, Peking University School of Oncology, Beijing.
¹⁴ Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
¹⁵ Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai.
¹⁶ Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
¹⁷ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai. Electronic address: tan.lijie@zs-hospital.sh.cn.

PMID: 36400384
DOI: 10.1016/j.annonc.2022.10.508

Abstract

Background: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC).

Patients and methods: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596).

Results: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802).

Conclusions: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

Keywords: esophageal squamous cell carcinoma; minimally invasive esophagectomy; neoadjuvant chemoradiotherapy; neoadjuvant chemotherapy; survival.

Publication types

Randomized Controlled Trial
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Chemoradiotherapy / methods
Esophageal Neoplasms* / drug therapy
Esophageal Squamous Cell Carcinoma* / therapy
Esophagectomy
Humans
Neoadjuvant Therapy / methods
Prospective Studies
Retrospective Studies

Associated data

ClinicalTrials.gov/NCT03001596