Esophagectomy versus definitive chemoradiotherapy for patients with clinical stage N0 and pathological stage T1b esophageal squamous cell carcinoma after endoscopic submucosal dissection: study protocol for a multicenter randomized controlled trial (Ad-ESD Trial)

Yang Yang,Bin Li,Jun Liu,Rong Hua,Hezhong Chen,Yuchen Su,Hong Zhang,Zhigang Li,Xiaobin Zhang,Lijie Tan

doi:10.1186/s13063-020-04461-5

Abstract

BackgroundEsophagectomy is still advised as an additional treatment for pathological T1b (pT1b) esophageal squamous cell carcinoma (ESCC) following attempted endoscopic resection (ER). ER followed with definitive chemoradiotherapy (dCRT) has shown increased quality of life as well as comparable oncological outcomes to esophagectomy. However, there is no well-designed phase III trial to compare the two treatments for patients with pT1b ESCC.MethodsOne hundred seventy-six patients with clinical stage N0 (cN0) and pT1b ESCC will be recruited at three centers and randomly assigned to the esophagectomy group or the dCRT group. The clinical lymph node status will be measured by image examination, including computer tomography and positron emission tomography–computed tomography. The pathological tumor status will be diagnosed after endoscopic submucosal dissection (ESD). All patients will be followed up for 60 months after randomization. The primary endpoint is 5-year overall survival. The secondary endpoints are quality of life, related adverse events, 3-year overall survival, and relapse-free survival rates.DiscussionTo the best of our knowledge, this is the first phase III randomized controlled trial to compare esophagectomy and dCRT for patients with cN0-pT1b ESCC after ESD. Based on the results of this study, we will show whether dCRT will benefit patients more than esophagectomy, which will contribute more high-quality evidence to the primary salvage treatment for these patients.Trial registrationClinicalTrials.gov, NCT04135664. Registered on Aug. 10, 2019.

Highlights

Background and rationale {6a} Esophageal cancer is the seventh most common malignant tumor and ranks sixth in tumor-related mortality worldwide [1]
The results showed that for patients with pathological T1b (pT1b) with R0 and pT1a with lymphovascular invasion (+) after endoscopic resection (ER), the 3-year overall survival (OS) was 90.7% (90% confidence interval 84.0%–94.7%) after prophylactic CRT
In an increasing numbers of patients, superficial lesions are treated primary with ER after receiving lymph node and distant metastasis evaluation

Summary

Methods

Study setting {9} Patients with cN0-pT1b ESCC after ESD will receive two concurrent salvage treatments. Recruitment {15} All patients with cN0-pT1b ESCC diagnosed after ESD treatment are potential candidates in this trial. The three institutions which are participating in this trial are high-volume medical centers with esophagectomy and ESD treatment. Procedure for unblinding if needed {17b} This trial is an open-label RCT with only statistical analysts being blinded to the procedure and the results of randomization, group allocation, and intervention. Data collection and management Plans for assessment and collection of outcomes {18a} After completion of allocated treatments, patients will be followed up until death or over a period of at least 60 months. Plans for communicating important protocol amendments to relevant parties (such as trial participants and ethics committees) {25} If the protocol needs to be modified, the PI (Zhigang Li) will set up a discussion meeting with all investigators in all three centers. The final trial dataset will be available to the investigative team and on reasonable request

Discussion

Introduction