Robotic-assisted Esophagectomy vs. Video-Assisted Thoracoscopic Esophagectomy(REVATE) Trial

Study Overview
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Brief Summary
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The investigators will assess the adequacy of nodal dissection along the recurrent laryngeal nerve performed with robot-assisted versus video-assisted thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma through a prospective multicentre randomized study design.

Detailed Description
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Radical lymph node dissection (LND) along the recurrent laryngeal nerve (RLN) is surgically demanding and can be associated with substantial postoperative morbidity. The question as to whether robot-assisted esophagectomy (RE) might be superior to video-assisted thoracoscopic esophagectomy (VATE) for performing LND along the RLN in patients with esophageal squamous cell carcinoma (ESCC) remains open. The investigators will conduct a multicenter, open-label, randomized controlled trial (termed REVATE) enrolling patients with ESCC scheduled to undergo LND along the RLN. Patients will be randomly assigned to either RE or VATE. The primary outcome measure will be the rate of unsuccessful LND along the left RLN, which will be defined as 1) failure to remove lymph nodes along the left RLN or 2) occurrence of left RLN palsy following LND. Secondary outcomes will include the number of successfully removed RLN nodes, postoperative recovery, length of hospital stay, 30- and 90-day mortality, quality of life, and oncological outcomes.

Official Title
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Robotic-assisted Esophagectomy vs. Video-Assisted Thoracoscopic Esophagectomy(REVATE) : a Multicenter Open-label Randomized Controlled Trial

Conditions
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Esophageal Squamous Cell Carcinoma

Intervention / Treatment
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* Device: Robot esophagectomy (RE)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Age between 18 80 Histologically proven primary intrathoracic esophageal squamous cell carcinoma and will undergo McKeown MIE and bilateral RLN LND. Patients should have a performance status 0, 1 or 2 according to the European Clinical Oncology Group. Surgical resectable(cT1 4a, N0 3, M0) Written informed consent Exclusion criteria are Previous major thoracic surgery rendering minimal invasive approach unfeasible prognosis determining malignancy other than esophageal cancer, inability to undergo curative resection and/or follow-up inability to provide oral or written informed consent. pre-existed vocal cord dysfunction will also be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Robot Esophagectomy (RE)<br>Patients in the RE group will receive robotic-assisted esophagectomy with standard total two-field lymphadenectomy. | Device: Robot esophagectomy (RE)<br>* Patients in RE group will receive Robotic-assisted surgery in thoracic phase.<br>|
| No Intervention: Video-assisted thoracoscopic esophagectomy (VATE)<br>Patients in the VATE group will receive thoracoscopic esophagectomy with standard total two-field lymphadenectomy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of unsuccessful LND along the left RLN | Regardless of the presence of hoarseness, vocal cord function will be assessed by an experienced otolaryngologist using a nexile laryngoscope within one week of surgery. RLN palsy will be classified according to the following variables: site (unilateral versus bilateral); duration (temporary [i.e., recovering within 6 months] versus permanent [i.e. not recovering within 6 months]); and type of treatment required (type I: no therapy required; type II: injury requiring an elective surgical procedure; type III: injury requiring an urgent surgical procedure) | Till 6 months postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of nodes removed along the right and left RLN | number of lymph node removed | The pathological analysis will be finished within 2 weeks. | 
| Post esophagectomy pneumonia rate | Post esophagectomy pneumonia is defined according to the Revised Uniform Pneumonia Score which includes temperature[°C](Range ≥ 36.1 and ≤ 38.4 =0, ≤ 36.0 and ≥ 38.5=1); leukocyte count [×1000/uL](≥ 4.0 and ≤ 11.0=0, <4.0 or >11.0=1); and pulmonary radiography(Range No infiltrate=0, Diffused or patchy infiltrate=1, Well-circumscribed infiltrate=2). A sum score of 2 points or higher, of which at least 1 point is assigned because of infiltrative findings on pulmonary radiography, indicates the presence of pneumonia. | Duration of hospital stay, an expected average of 2 3 weeks | 
| Rate of major postoperative complication | Complication grade: modified Clavien-Dindo classification (MCDC) grade 2-4 Major complications (MCDC grade 2-4) Including: myocardial infarction, 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, deep vein thrombosis. Minor complications (MCDC grade 1) Including: wound infections, pleural effusions, delayed gastric emptying | Duration of hospital stay, an expected average of 2 3 weeks | 
| In hospital, 30 day and 90 day mortality | Death occurred during the same hospitalization , within 30 and 90 days after surgery | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks and within 30 days or 90 days | 
| R0 resection rate | Microscopically negative proximal/distal and circumferential margin | The pathological analysis will be finished within 2 weeks. | 
| Operation time(thoracic phase) | thoracic phase operation time(minutes) | Day of surgery | 
| Operation time(abdominal) | abdominal phase operation time(minutes) | Day of surgery | 
| Total operation time | total surgical time (expressed in minutes) | Day of surgery | 
| Unexpected events and complications occurring during surgery | massive hemorrhage, perforation of other organs | Day of surgery, up to 24 hours after surgery. | 
| Blood loss during surgery | blood loss during surgery (expressed in mL per phase) | Day of surgery, up to 24 hours after surgery. | 
| Rate of thoracotomy conversion | Number of patients requiring conversion to thoracotomy and related reasons | Day of surgery, up to 24 hours after surgery. | 
| Length of mechanical ventilator use after surgery | expressed in minutes | Participants will be followed for the duration of hospital stay, an expected average of 2 3 weeks | 
| Length of intensive care unit stay after surgery | expressed in hours | Participants will be followed for the duration of hospital stay, an expected average of 2 3 weeks | 
| Length of postoperative hospital stay | expressed in days , calculated from the date of surgery to date of discharge | Participants will be followed for the duration of hospital stay, an expected average of 2 3 weeks | 
| Re-intubation rate | Need for re-intubation after extubation | Participants will be followed for the duration of hospital stay, an expected average of 2 3 weeks | 
| Re-entry ICU rate | Need to transfer back from ward to ICU after surgery | Participants will be followed for the duration of hospital stay, an expected average of 2 3 weeks | 
| Overall survival rate | From date of surgery until the date of death from any cause | Assessed 24/36/60 months after surgery | 
| Disease free survival rate | From date of surgery until the date of first documented recurrence | Assessed up to 24/36/60 months after surgery | 
| Hospital Anxiety and Depression Scale (HADS) | The HADS aims to measure symptoms of anxiety and depression and consists of 14 items,seven items for the anxiety subscale and seven for the depression subscale. The questionnaire responses were analysed in the light of the results of this estimation of the severity of both anxiety and of depression. This enabled a reduction of the number of items in the questionnaire to just seven reflecting anxiety and seven reflecting depression.(Of the seven depression items five reflected aspects of reduction in pleasure response). Each item had been answered by the patient on a four point (0-3) response category so the possible scores ranged from 0 to 21 for anxiety and 0 to 21 for depression. a score of 0 to 7 for either subscale could be regarded as being in the normal range, a score of 11 or higher indicating probable presence ('caseness') of the mood disorder and a score of 8 to 10 being just suggestive of the presence of the respective state. | pre-operative < 5 days and 4 weeks, 3/6 months and yearly up to 5 years post-operatively. | 
| European Organisation for Research and Treatment of Cancer(EORTC) QLQ-C30 , QLQ-OES18 | The EORTC QLQ-C30 incorporates a range of QOL issues in five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea/vomiting), a global health/QOL scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The EORTC QLQ-OES18 contains four symptom scales (dysphagia, eating disorders, reflux, and pain) and six single items (difficulty swallowing saliva, choking, dry mouth, taste disorder, cough, and speech-related issues). Each question has four response choices ranging from 1 (not at all) to 4 (very much), except for the global QOL scale, which has seven response options ranging from 1 (very poor) to 7 (excellent). All questionnaire responses are linearly transformed to scores from 0 to 100. | pre-operative < 5 days and 4 weeks, 3/6 months and yearly up to 5 years post-operatively. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Robotic esophagectomy, Video-assisted thoracoscopic esophagectomy, Recurrent laryngeal nerve lymh node, Esophageal squamous cell carcinoma