Robotic Versus Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy for Locally Advanced Gastric Cancer

Study Overview
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Brief Summary
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This study is an investigator-initiated, randomized, controlled, parallel group, and non-inferiority trial comparing robot-assisted gastrectomy with D2 nodal dissection for locally advanced gastric cancer patients with laparoscopic procedure.

Detailed Description
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Since the first case of laparoscopy-assisted distal gastrectomy was reported in 1994, the number of patients undergoing the laparoscopic procedure has gradually increased. The latest Japanese gastric cancer treatment guideline recommends laparoscopic gastrectomy (LG) as an optional treatment for cStage I gastric cancer (GC). Based on the experience of early GC, most experienced surgeons have applied the laparoscopic procedure in patients with locally advanced gastric cancer (AGC). According to the results of large-scaled retrospective studies and ongoing randomized controlled trials (RCTs), LG treating AGC can gain better short-term outcomes and comparable long-term oncologic results. To minimize the limitations of laparoscopic surgery, robot systems have been introduced to treat GC providing technical advantages. Though the feasibility and safety of robotic gastrectomy (RG) have been well accepted, the benefits of RG remain controversial. A recent meta-analysis including eleven studies of 3503 patients demonstrated that RG indicated potentially favorable outcomes in terms of blood loss compared with LG. Furthermore, it has been confirmed that robotic system could provide an advantage over LG in the dissection of the N2 area lymph nodes, especially around the splenic artery area. Our previous study demonstrated that the RG had less intraoperative blood loss and more lymph nodes dissection compared with the laparoscopic procedure. However, the only prospective study reported that RG is not superior to LG in terms of perioperative surgical outcomes. Nevertheless, the following subgroup analysis found that patients with GC undergoing D2 lymph node dissection can benefit from less blood loss when a robotic surgery system is used. Take together, RG with D2 nodal dissection may be superior laparoscopic surgery in terms of blood loss and retrieved lymph nodes. However, lack of high-level evidence-based medical researches, we can't drew a conclusion that patients with AGC may benefit from RG with D2 nodal dissection. With regard to a new surgical approach, oncologic safety has attracted more attention. Although some retrospective studies have demonstrated that RG with lymphadenectomy for GC had non-inferior oncologic outcome relative to LG, there is no prospective RCT to evaluate the long-term outcomes of RG. Therefore, the Chinese Robotic Gastrointestinal Surgery Study (CRASS) Group launched a multicenter prospective RCT to verify the short-term and long-term outcomes of RG in AGC. The primary objective of this study is to assess whether robot-assisted distal gastrectomy is comparable to laparoscopic approach in terms of long-term oncologic outcomes without compromising relapse-free survival. The secondary research objectives are to compare robotic and laparoscopic approach in terms of morbidity, mortality, quality of life, cost-effectiveness, and overall survival.

Official Title
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Robotic Versus Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy for Locally Advanced Gastric Cancer: a Multicenter Randomized Controlled Trial

Conditions
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Gastric Cancer

Intervention / Treatment
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* Procedure: Robotic distal gastrectomy with D2 nodal dissection
* Procedure: Laparoscopic distal gastrectomy with D2 nodal dissection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven gastric adenocarcinoma. Tumor located in the lower third of the stomach, and is possible to be curatively resected by subtotal gastrectomy. Preoperative stage of cT2-4aN0-3M0 according to American Joint Committee on Cancer/Union for International Cancer Control 8th edition Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 American Society of Anesthesiology (ASA) score of class I to III Patients who freely give informed consent to participate in the clinical study Exclusion Criteria: Previous upper abdominal surgery (except laparoscopic cholecystectomy) Previous gastric resection (gastrectomy, endoscopic mucosal resection, or endoscopic submucosal dissection) Gastric cancer-related complications (complete obstruction or perforation) Enlarged or bulky regional lymph node diameter larger than 3 cm based on preoperative imaging Previous neoadjuvant chemotherapy or radiotherapy for gastric cancer Patients diagnosed with other malignancy within 5 years Severe mental disorder Unstable angina or myocardial infarction within the past 6 months Cerebrovascular accident within the past 6 months Severe respiratory disease (FEV1< 50%) Continuous systemic steroid therapy within 1 month before the study Pregnant or breast-feeding women

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Robotic gastrectomy<br>Robotic distal gastrectomy with D2 nodal dissection | Procedure: Robotic distal gastrectomy with D2 nodal dissection<br>* After exclusion of T4b, bulky lymph nodes, or distant metastasis case by diagnostic laparoscopy, robotic distal gastrectomy with D2 lymph node dissection will be performed with curative treated intent.The type of reconstruction will be determined by the surgeon's experience and preference. The reconstruction can be carried out by extracorporeal or intracorporeal anastomosis.<br>|
| Active Comparator: Laparoscopic gastrectomy<br>Laparoscopic distal gastrectomy with D2 nodal dissection | Procedure: Laparoscopic distal gastrectomy with D2 nodal dissection<br>* After exclusion of T4b, bulky lymph nodes, or distant metastasis case by diagnostic laparoscopy, laparoscopic distal gastrectomy with D2 lymph node dissection will be performed with curative treated intent.The type of reconstruction will be determined by the surgeon's experience and preference. The reconstruction can be carried out by extracorporeal or intracorporeal anastomosis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year relapse-free survival | Relapse-free survival is defined as days from surgery to recurrence or death from any cause, and it is censored at the latest day when the patient is alive without any evidence of recurrence. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity | Early postoperative morbidity confined to events that occur within 30 days after surgery. The complications that occur after postoperative day 30 belong to late postoperative morbidity | 30 days | 
| Mortality | Postoperative mortality is defined to death that occurs within 30 days. | 30 days | 
| 3-year overall survival | Overall survival is defined as days from surgery to death from any cause, and it is censored at the last day when the patient was alive. | 3 years | 
| 3-year recurrence pattern | Recurrence patterns are classified into five categories at the time of first diagnosis: locoregional, hematogenous, peritoneal, distant lymph node, and mixed type. | 3 years | 
| Postoperative recovery course | Time to first ambulation, flatus, liquid diet, soft diet, and duration of hospital stay are used to assess the postoperative recovery course. | 15 days | 
| Inflammatory response | The daily highest body temperature before discharge and the values of white blood cell count (10^9/L), hemoglobin (g/L), C-reactive protein (mg/L) and prealbumin (mg/L) from peripheral blood before operation and on postoperative day 1, 3, 5, 7 are recorded. | 7 days | 
| Immune response | The values of relevant immune cytokines from peripheral blood before operation and on postoperative day 1, 3, 5, 7 are recorded. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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laparoscopy-assisted gastrectomy, robot-assisted gastrectomy, advanced gastric cancer, D2 Lymphadenectomy