Resecable Esophageal or Gastroesophageal Junction Cancer
Conditions
Keywords
Cancer, oesophagectomy, minimally invasive, Robot-assisted surgery
Brief summary
Esophageal and gastroesophageal junction cancers remain associated with poor survival despite progress in multimodal treatment. Surgery, especially Ivor-Lewis esophagectomy, combined with peri-operative therapy improves survival but is burdened by major morbidity, mainly respiratory and anastomotic complications, which compromise recovery and adjuvant treatment. Minimally invasive approaches such as totally minimally invasive esophagectomy (TMIE) have shown potential to reduce postoperative morbidity compared to the hybrid approach (HE). However, existing studies are heterogeneous, mostly retrospective, and insufficient to establish a standard. This trial aims to provide high-level evidence comparing TMIE to HE, including robotic techniques, with integrated analyses of clinical outcomes, quality of life, and health economics.
Interventions
PROCEDURETotally Minimally Invasive Esophagectomy (TMIE)
All patients will undergo an Ivor-Lewis procedure with the same laparoscopic abdominal approach. The thoracic approach differs between the two groups: HE with open thoracotomy in the 5th or 6th intercostal space and TMIE with thoracoscopic approach. The main aspects of the surgical technique will be standardized. All patients will receive a transthoracic en-bloc esophagectomy with termino-lateral or latero-lateral anastomosis in the upper chest, including an abdominal lymphadenectomy (left and right paracardial regions along the lesser curve of the left gastric artery, celiac axis, origin of the common hepatic artery and splenic artery) and an extended en bloc mediastinal lymphadenectomy including paratracheal, subcarinal, left and right bronchial, lower posterior mediastinum, para-aortic, para-esophageal lymph with or without resection of the thoracic duct), i.e., an extended two- field lymphadenectomy. The esophagus will be replaced by the stomach in all cases.
PROCEDUREHybrid Esophagectomy (HE)
All patients will undergo an Ivor-Lewis procedure with the same laparoscopic abdominal approach. The thoracic approach differs between the two groups: HE with open thoracotomy in the 5th or 6th intercostal space and TMIE with thoracoscopic approach. The main aspects of the surgical technique will be standardized. All patients will receive a transthoracic en-bloc esophagectomy with termino-lateral or latero-lateral anastomosis in the upper chest, including an abdominal lymphadenectomy (left and right paracardial regions along the lesser curve of the left gastric artery, celiac axis, origin of the common hepatic artery and splenic artery) and an extended en bloc mediastinal lymphadenectomy including paratracheal, subcarinal, left and right bronchial, lower posterior mediastinum, para-aortic, para-esophageal lymph with or without resection of the thoracic duct), i.e., an extended two- field lymphadenectomy. The esophagus will be replaced by the stomach in all cases.
Sponsors
University Hospital, Lille
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
National, multicentric, phase III, open-label, randomized controlled trial with two parallel arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria for screening - part A (for patients receiving a neo-adjuvant treatment) * Age ≥ 18 years and ≤ 80 years For patients between 70 and 80 years old : score G8 ≥ 14 or oncogeratrician approval * Squamous cell carcinoma or adenocarcinoma of the esophagus or esogastric junction * Clinical stage T1, T2, T3, T4a, N0-N3, M0 before any treatment * Tumors of the middle or lower third of the esophagus, or tumor of the esogastric junction Siewert 1 or 2 * With or without neoadjuvant (radio) chemotherapy ± targeted therapy * Disease deemed curatively resectable preoperatively * Requiring a 2-stage Ivor-Lewis esophagectomy * Performance status 0, 1 or 2 * Patient capable of receiving either surgical treatment * Patient informed of the terms of the study and having given written consent * Patient able to read and understand the language and content of the study documents and agreeing to adhere to the protocol requirements. * Covered by a medical/health insurance * Willingness and ability to comply with scheduled visits and study procedures Inclusion criteria before surgery (after neo-adjuvant treatment or for patients receiving primary surgery) * Age ≥ 18 years and ≤ 80 years For patients between 70 and 80 years old : score G8 ≥ 14 or oncogeratrician approval * Squamous cell carcinoma or adenocarcinoma of the esophagus or esogastric junction * Clinical stage T1, T2, T3, N0-N3, M0 before surgery * Tumors of the middle or lower third of the esophagus, or tumor of the esogastric junction Siewert 1 or 2 * With or without neoadjuvant (radio) chemotherapy ± targeted therapy * Disease deemed curatively resectable preoperatively * Requiring a 2-stage Ivor-Lewis esophagectomy * Performance status 0, 1 or 2 * Patient capable of receiving either surgical treatment * Patient informed of the terms of the study and having given written consent * Patient able to read and understand the language and content of the study documents and agreeing to adhere to the protocol requirements. * Covered by a medical/health insurance * Willingness and ability to comply with scheduled visits and study procedures
Exclusion criteria
Non inclusion criteria for screening - part A (for patients receiving a neo-adjuvant treatment) Patient-related non-inclusion criteria * Performance status 3 or 4 * Documented liver cirrhosis or portal hypertension * Recent myocardial infarction (less than 6 months old) or progressive coronary artery disease * Distal arteritis from stage IIb (200 m) of Leriche and Fontaine * Synchronous cancer, other than subcarinal esophageal * Neoplasic history except for cancers without recurrence after at least 5 years of surveillance * History of xyphopubic laparotomy * Patients with prior thoracic surgery or thoracic traum of the right hemithorax * Patient refusal * Patient under guardianship or curatorship * Pregnant or breastfeeding woman or patient expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 6 months after the last dose of adjuvant chemotherapy * ASA score\> 3 Disease-related non-inclusion criteria * Histology other than squamous cell carcinoma or adenocarcinoma * Tumors of the upper third of the thoracic esophagus, cervical esophagus or pharyngo-esophageal junction or tumor of the esogastric junction Siewert 3 * Supraclavicular nodes invaded clinically or on puncture * Recurrent nerve paralysis * Evidence of extension to the tracheobronchial tree * Signs of mediastinal invasion (vertebral adhesion, aortic overlap \> 90°, invasion of unresectable neighboring organs such as the aorta, trachea…) * Distant metastatic extension Non inclusion criteria before surgery (after neo-adjuvant treatment or for patients receiving primary surgery) * Performance status 3 or 4 * Forced expiratory volume in 1 second \< 1000 ml * Documented liver cirrhosis or portal hypertension * Recent myocardial infarction (less than 6 months old) or progressive coronary artery disease * Distal arteritis from stage IIb (200 m) of Leriche and Fontaine * Weight loss of more than 15% of body weight, not recovered after appropriate nutritional management * Synchronous cancer, other than subcarinal esophageal * Neoplasic history except for cancers without recurrence after at least 5 years of surveillance * History of xyphopubic laparotomy * Patients with prior thoracic surgery or thoracic traum of the right hemithorax * Patient refusal * Patient under guardianship or curatorship * Pregnant or breastfeeding woman or patient expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 6 months after the last dose of adjuvant chemotherapy * ASA score\> 3 * IESG ≤ -5 (Very high risk patients) Disease-related non-inclusion criteria * Histology other than squamous cell carcinoma or adenocarcinoma * Tumors of the upper third of the thoracic esophagus, cervical esophagus or pharyngo-esophageal junction or tumor of the esogastric junction Siewert 3 * Supraclavicular nodes invaded clinically or on puncture * Recurrent nerve paralysis * Evidence of extension to the tracheobronchial tree * Signs of mediastinal invasion (vertebral adhesion, aortic overlap \> 90°, invasion of unresectable neighboring organs such as the aorta, trachea…) * Distant metastatic extension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severe postoperative complications after surgery. | 90 days | Severe postoperative complications after surgery, defined as any postoperative complication of grade 3 or higher according to the Clavien-Dindo (grade III : requiring surgical, endoscopic or radiological intervention (not under general anesthesia) to grade V : death of a patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of patients experiencing complication equal to or greater than 2 according to the Clavien-Dindo classification | 90 days | Clavien-Dindo (grade III : requiring surgical, endoscopic or radiological intervention (not under general anesthesia) to grade V : death of a patient. |
| Rate of patients experiencing complication equal to or greater than 2 according to the Comprehensive Complication Index scale (0 = no complications, 100 = Death) | 90 days | — |
| Respiratory complication rate | 90 days | respiratory complication rate is defined as any respiratory event detailed by the ECCG classification (Esophagectomy Complications Consensus Group), including pneumonia, pleural effusion requiring additional drainage procedure, pneumothorax requiring intervention, atelectasis mucous plugging requiring bronchoscopy, respiratory failure requiring reintubation, acute respiratory distress syndrome, acute aspiration, tracheobronchial injury and chest drain requirement for air leak for more than 10 days postoperatively |
| Anastomotic leak rate | 90 days | anastomotic leak rate defined as full thickness GI defect involving esophagus, anastomosis, staple line, or conduit irrespective of presentation or method of identification. Anastomotic leaks will be classified into 3 types according to the treatment required, according to the international classification. |
| Mortality rate | 90 days | The mortality is defined as any death occurring within 90 days of surgery. |
| Length of stay in the ICU. | 90 days | The length of stay in the ICU is defined as the number of postoperative days within 90 days of surgery |
| Length of hospital stay. | 90 days | The length of hospital stay is defined by the number of postoperative days the patient spends in the intensive care unit or in a conventional ward. |
| Level of pain | 14 days | The level of pain during the first 14 days after surgery is assessed by visual analog scale (score from 0 = no pain, to 10 = wort imaginable pain) on a daily basis, from the day of surgery until 14 days after surgery or until discharge of the patient. |
| Presence of neuropathic pain | 6 months | neuropathic pain will be assessed using the Neuropathic Pain Symptom Inventory (NPSI) (from 0 = not present to 10 = worst imaginable). |
| Change from baseline in quality of life level | 1 months, 6 months, 1 year, 3 years, 5 years | The change from baseline (before surgery, V1) in quality of life level on validated EORTC QLQC-30 (European Organisation for Research and Treatment of Cancer Quality of Life Core 30) questionnaire at 1 month, 6 months, 1 year, 3 years and 5 years postoperatively. |
Countries
France
Contacts
CONTACTThibault VORON, Dr
CONTACTGuillaume PIESSEN, Pr
Outcome results
None listed