Adjuvant 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)

Background: Esophagectomy is still the prior additional treatment for pathological T1b (pT1b) esophageal squamous cell carcinoma (ESCC) after endoscopic resection (ER). ER followed with definitive chemoradiotherapy (dCRT) has showed 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 treatment for patients with pT1b ESCC. Methods: One hundred seventy-six patients with clinical stage N0 (cN0) and pT1b ESCC will be recruited at three centers and randomized 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 the 5-year overall survival. The secondary endpoints are quality of life, related adverse events, 3-year overall survival and relapse-free survival rates. Discussion: To the best of our knowledge, this is the first phase III randomized controlled trial to compare the 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 registration : ClinicalTrials.gov, NCT04135664. Registered on 10 August 2019.