Robot-assisted Thoracic Approach Versus Open Transthoracic Esophagectomy .

Study Overview
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Brief Summary
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This is a randomized controlled trial designed to compare robot-assisted thoracic approach with open transthoracic esophagectomy (Ivor Lewis technique) as a surgical treatment for resectable esophageal cancer. If our hypothesis is proved correct, robot-assisted thoracic approach will result in a lower percentage of respiratory and overall postoperative complications, lower blood loss, shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with the open transthoracic esophagectomy (current standard).

Detailed Description
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Rationale: Esophageal cancer represents the fifth most common tumor of cancers of the digestive system in Spain, between the ten most common cancers and the sixth leading cause of cancer death in the world. Among the standard modalities for treatment with curative intention, surgery is available, in combination with neoadjuvant (pre-surgery) and/or adjuvant (post-surgery) chemotherapy and radiation therapy. Esophageal surgery is crucial to improve overall survival in patients with esophageal cancer. Surgical treatment is based on esophageal resection and reconstruction of digestive transit, as well as a correct lymphadenectomy. One of the techniques used is Ivor Lewis transthoracic esophagectomy. Classically, thoracic approach has been done by open approach (thoracotomy), with minimally invasive (laparoscopy) abdominal approach, a reality in our centre and in most European centres. Postoperative comorbidity, specially respiratory complications, occur approximately in half of patients with esophagectomy with thoracotomy (open approach). Although current clinical trials have reported advantages over minimally invasive esophagectomy (MI), at the time, most esophageal surgery is performed by open approach. More studies are needed to clarify the role of minimally invasive esophagectomy in esophageal cancer, so as to provide evidence about the comorbidity and effectiveness of surgical robot-assisted technique. If our hypothesis is proved correct, robot-assisted thoracic approach will result in a lower percentage of respiratory and overall postoperative complications, lower blood loss, shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with the open transthoracic esophagectomy (current standard). Objective: Evaluate the benefits, risks and cost-efficiency of Robot-assisted thoracic approach as a better approach to open transthoracic Ivor Lewis esophagectomy as treatment for esophageal cancer. Study design: This is an investigator-initiated and investigator-driven monocentre randomized controlled parallel-group, phase IV, superiority trial. Study populations: Patients (age ≥ 18) with histologically proven surgical resectable (cT1-4a, N0-3, M0) adenocarcinoma, squamous cell carcinoma, undifferentiated esophageal carcinoma or carcinomas of the esophagogastric junction (EGJ) (Siewert I or II) candidate to Ivor Lewis Esophagectomy. Intervention:108 patients will be randomly allocated to either A) Robot-assisted thoracic approach or B) Open transthoracic esophagectomy, in Ivor Lewis technique. In both groups the abdominal approach will be performed by laparoscopy (minimally invasive). Patients will receive the following interventions: Group A. Robot-assisted thoracic approach in Ivor Lewis esophagectomy. Group B. Open transthoracic approach (thoracotomy) in Ivor Lewis esophagectomy. Both surgical techniques are used in our usual clinical practice of the General and Digestive Surgery Department of the Bellvitge University Hospital (HUB). Main study parameters/endpoints: Primary outcome is the percentage of respiratory and overall complications as stated by the modified Clavien-Dindo classification (MCDC). Secondary outcomes are individual components of the primary endpoint (major and minor complications), (in hospital) mortality, R0 resections, oncologic outcomes, postoperative recovery, cost-effectiveness and quality of life. Follow-up:84±3 days after hospital discharge. NOTE: The project consists of a clinical trial and an extension study to assess the free-survival of 3 and 5 years from surgery.

Official Title
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Clinical Trial Of Safety Of Robot-assisted Thoracic Approach Verus Open Transthoracic Esophagectomy in Esophageal Cancer.

Conditions
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Esophageal Cancer, Esophageal Carcinoma, Postoperative Complications

Intervention / Treatment
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* Procedure: Esophagectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Histologically proven adenocarcinoma, squamous cell carcinoma, undifferentiated carcinoma or carcinoma of the gastro-esophageal junction (GEJ) Siewert I or II. Surgical resectable (T1-4a, N0-3, M0). Childbearing potential women (period between menarche and menopause), pregnancy negative test is mandatory. Written informed consent. Exclusion Criteria: Stage IV or GEJ Siewert III esophageal cancer. Contraindication of transthoracic esophagectomy in two fields. Pre- or concomitant cancer or conditions which interferes with the study (e.g. prior thoracic surgery or trauma. Rationale: these patients may undergo open resection).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Monocentre randomized controlled parallel-group, phase IV, superiority trial. The main purpose is to demonstrate the superiority of robot-assisted thoracic approach over thoracotomy (conventional surgery) in decreasing respiratory and overall complications in Ivor Lewis-type esophagectomy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Robot-assisted thoracic approach in Ivor Lewis esophagectomy<br>Robot-assisted thoracic approach in Ivor Lewis esophagectomy with gastric conduit formation. Abdominal approach will be performed by laparoscopy. | Procedure: Esophagectomy<br>* In this monocentre randomized controlled trial, we compare robot-assisted thoracic approach with conventional open transthoracic Ivor Lewis esophagectomy.<br>* Other names: Robot-assisted thoracic approach in Ivor Lewis esophagectomy;|
| Active Comparator: Open transthoracic approach in Ivor Lewis esophagectomy<br>Traditional open transthoracic esophagectomy with gastric conduit formation. Abdominal approach will be performed by laparoscopy. | Procedure: Esophagectomy<br>* In this monocentre randomized controlled trial, we compare robot-assisted thoracic approach with conventional open transthoracic Ivor Lewis esophagectomy.<br>* Other names: Robot-assisted thoracic approach in Ivor Lewis esophagectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory postoperative complications. | The primary outcome of this study is the percentage of respiratory complications as stated by the modified Clavien-Dindo classification of surgical complications (MCDC). by means of AME chest approach by robot and thoracotomy (classic surgery). | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks up to 84+/-3 days from hospital discharge. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative complications. | Estimate the percentage of overall complications as stated by the modified Clavien-Dindo classification of surgical complications (MCDC) by means of Robot-assisted thoracic approach and thoracotomy (classic surgery). | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks up to 84+/-3 days from hospital discharge. | 
| Individual components of the primary endpoint (major and minor complications). | Major complications (MCDC Grade 2-4): anastomotic leakage (clinical or radiologic diagnosis), anastomotic stenosis, chylothorax (chylous leakage, presence of chylous in chest tubes or indication start medium chain triglycerides containing tube feeding), gastric tube necrosis (proven by gastroscopy), pulmonary embolus, pneumothorax, deep vein thrombosis, myocardial infarction, vocal cord palsy or paralysis. Minor complications (MCDC Grade 1): wound infections, pleural effusions, delayed gastric emptying. All these postoperative complications will be properly and separately recorded in the electronic collection database. | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks up to 84+/-3 days from hospital discharge | 
| Postoperative mortality (during hospital stay up to 84+/-3 days after discharge). | (In hospital) mortality and mortality within 14+/-2 days and 84+/-3 days after hospital discharge will be reported. The cause of death will be noted. | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks up to 84+/-3 days from hospital discharge. | 
| Operation related events. | Operation time is defined as time from incision until closure (minutes) for both the thoracic and the abdominal phase of the procedure. For the robotic approach, set up time will be recorded separately. Unexpected events and complications occuring during operation will be recorded (e.g. massive hemorrhage, perforation of other organs). Blood loss during operation (ml, per phase). In case of conversion to thoracotomy or laparotomy the reason for conversion has tp be explained (absolute numbers/percentage). | Day of surgery, up to 24 hours after surgery. | 
| Postoperative recovery. | Pain: type and dose of used analgesics will be noted during the hospital admission period and noted during the follow-up period. Unit of measure: Visual Analog Score for pain. Length of intensive care unit (ICU) (days). Length of hospital stay (days). | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks. | 
| R0 resections (%). | The pathological analysis will be finished within 2-3 weeks after surgery. | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks and 14+/- days after discharge. | 
| Oncologic outcomes. | Overall survival within the first 84+/-3 days. NOTE: 2, 3 and 5 year disease free and overall survival will be reported in the study of extension . | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 84+/-3 days after discharge. | 
| Postoperative quality of life. | Postoperative quality of life will be assessed through Physicians Global Assessment to measure quality of life: Questionnaires EORTC QLQ-C30 and EQ-5D will be required from 14+/-2 up to 84+/-3 days after hospital discharge. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 84+/-3 days after discharge. |