The CARDIA-trial protocol: a multinational, prospective, randomized, clinical trial comparing transthoracic esophagectomy with transhiatal extended gastrectomy in adenocarcinoma of the gastroesophageal junction (GEJ) type II

• Published in: BMC cancer Vol. 20; no. 1; p. 781
• Main Authors: Leers, Jessica M, Knepper, Laura, van der Veen, Arjen, Schröder, Wolfgang, Fuchs, Hans, Schiller, Petra, Hellmich, Martin, Zettelmeyer, Ulrike, Brosens, Lodewijk A A, Quaas, Alexander, Ruurda, Jelle P, van Hillegersberg, Richard, Bruns, Christiane J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.08.2020; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adult; Cardia - pathology; Cardia - surgery; cardia carcinoma; Cardiovascular disease; Chemotherapy; Clinical medicine; Clinical trials; Consent; Cost analysis; Cost-Benefit Analysis; Disease-Free Survival; Ejection fraction; Endoscopy; Equivalence Trials as Topic; esophageal adenocarcinoma; Esophageal cancer; Esophageal Neoplasms - economics; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophageal Neoplasms - surgery; esophagectomy; Esophagectomy - adverse effects; Esophagectomy - methods; Esophagogastric Junction - pathology; Esophagogastric Junction - surgery; Esophagus; Esophagus - pathology; Esophagus - surgery; Europe - epidemiology; Female; Follow-Up Studies; Gastrectomy; Gastrectomy - adverse effects; Gastrectomy - economics; Gastrectomy - methods; gastroesophageal junction; Gastrointestinal surgery; Humans; Localization; Lymph Node Excision; Lymph nodes; Lymphatic system; Male; Margins of Excision; Metastasis; Multicenter Studies as Topic; Patients; Postoperative Complications - economics; Postoperative Complications - epidemiology; Postoperative Complications - etiology; Prospective Studies; Quality control; Quality of Life; Randomized Controlled Trials as Topic; Siewert type II; Stomach Neoplasms - economics; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Study Protocol; Surgery; Survival; Tumor removal; Tumors; Europe; Netherlands; Siewert type II; esophagectomy; gastroesophageal junction; gastrectomy; esophageal adenocarcinoma; cardia carcinoma
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-07152-1

Adenocarcinoma of the gastroesophageal junction (GEJ) Siewert type II can be resected by transthoracic esophagectomy or transhiatal extended gastrectomy. Both allow for a complete tumor resection, yet there is an ongoing controversy about which surgical approach is superior with regards to quality of life, oncological outcomes and survival. While some studies suggest a better oncological outcome after transthoracic esophagectomy, others favor transhiatal extended gastrectomy for a better postoperative quality of life. To date, only retrospective studies are available, showing ambiguous results. This study is a multinational, multicenter, randomized, clinical superiority trial. Patients (n = 262) with a GEJ type II tumor resectable by both transthoracic esophagectomy and transhiatal extended gastrectomy will be enrolled in the trial. Type II tumors are defined as tumors with their midpoint between ≤1 cm proximal and ≤ 2 cm distal of the top of gastric folds on preoperative endoscopy. Patients will be included in one of the participating European sites and are randomized to either transthoracic esophagectomy or transhiatal extended gastrectomy. The trial is powered to show superiority for esophagectomy with regards to the primary efficacy endpoint overall survival. Key secondary endpoints are complete resection (R0), number and localization of tumor infiltrated lymph nodes at dissection, post-operative complications, disease-free survival, quality of life and cost-effectiveness. Postoperative survival and quality of life will be followed-up for 24 months after discharge. Further survival follow-up will be conducted as quarterly phone calls up to 60 months. To date, as level 1 evidence is lacking, there is no consensus on which surgery is superior and both surgeries are used to treat GEJ type II carcinoma worldwide. The CARDIA trial is the first randomized trial to compare transthoracic esophagectomy versus transhiatal extended gastrectomy in patients with GEJ type II tumors. Several quality control measures were implemented in the protocol to ensure data reliability and increase the trial's significance. It is hypothesized that esophagectomy allows for a higher rate of radical resections and a more complete mediastinal lymph node dissection, resulting in a longer overall survival, while still providing an acceptable quality of life and cost-effectiveness. The trial was registered on August 2nd 2019 at the German Clinical Trials Register under the trial-ID DRKS00016923 .