RATME vs LATME in Middle and Low Rectal Cancer

Study Overview
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Brief Summary
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This is a multicenter, superior, randomized controlled trial designed to compare Robotic-assisted total mesorectal excision (RATME) and laparoscopic-assisted total mesorectal excision (LATME) for middle and low rectal cancer. The primary endpoint is the incidence of intersphincteric resection (ISR). The secondary outcomes are coloanal anastomosis (CAA), conversion to open, conversion to transanal TME (TaTME), incidence of abdominoperineal resection (APR), postoperative morbidity and mortality within 30 days after surgery, pathological outcomes, long-term survival outcomes, functional outcomes, and quality of life.

Detailed Description
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Robotic-assisted total mesorectal excision (RATME) has been gradually applied by colorectal surgeons. Most surgeons consider RATME a safe method and believe it can facilitate total mesorectal excision (TME) in rectal cancer, especially middle and low rectal cancer with a narrow pelvis. Therefore, this trial investigates whether RATME has technical advantages and increase intersphincteric resection rate compared with laparoscopic-assisted TME (LATME) in middle and low rectal cancer. This is a multicenter, superior, randomized controlled trial designed to compare RATME and LATME for middle and low rectal cancer. The primary endpoint is the incidence of intersphincteric resection (ISR). The secondary outcomes are coloanal anastomosis (CAA), conversion to open, conversion to transanal TME (TaTME), incidence of abdominoperineal resection (APR), postoperative morbidity and mortality within 30 days after surgery, pathological outcomes, long-term survival outcomes, functional outcomes, and quality of life. In addition, certain measures will be conducted to ensure quality and safety, including centralized photography review and semiannual assessment.

Official Title
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A Multicenter Randomized Clinical Trial to Assess the Advantages of Robotic Total Mesorectal Excision in Preserving External Sphincter in Patients With Middle and Low Rectal Cancer.

Conditions
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Total Mesorectal Excision, Rectal Neoplasms, Robotic Surgical Procedures, Laparoscopy

Intervention / Treatment
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* Procedure: Robotic-assisted total mesorectal excision
* Procedure: laparoscopic-assisted total mesorectal excision


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male patients diagnosed with rectal cancer by pathological biopsy; abdominal contrast-enhanced and chest computed tomography (CT) or positron emission tomography-computed tomography (PET-CT) revealed no distal metastasis; Preoperative rectal magnetic resistance (MR) evaluation showed that the tumor was located at or below the peritoneal reflux plane, and at least 1cm above the anal sphincter groove, and did not invade the external anal sphincter; Tumors located above the hiatus of levator ani muscle were evaluated by magnetic resonance imaging as cT1-3, cN0-1, M0, and MRF (-); The tumors located below the hiatus of levator ani muscle were evaluated by magnetic resonance imaging as cT1-2, cN0-1, M0, and MRF (-). After neoadjuvant treatment, the tumor above the hiatus of levator ani muscle is ycT3NxM0 or below; The tumor below the hiatus of levator ani muscle is ycT2NxM0; The patient underwent laparoscopic assisted TME surgery or robotic assisted TME surgery. Exclusion Criteria: multiple primary cancers; history of open surgery; no preoperative MR evaluation and inadequate evaluation of tumor stage; Patients with rectal cancer who undergo endoscopic resection first and need subsequent transabdominal resection; Pregnant or patients with concomitant inflammatory bowel disease; Patients with preoperative complete bowel obstruction or requiring emergency surgery; Preoperative evaluation indicates that patient may require combined organ resection; Recently receiving treatment for other malignant tumors; Bordeaux type IV low rectal cancer; The preoperative pathological types are signet ring cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, or poorly differentiated carcinoma. Exit Criteria Refuse surgical treatment after randomization; Open surgery was performed for treatment after randomization; Patients request to withdraw from the study at any time during the entire study process after randomization

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: RATME<br>In RaTME groups, the low anterior resection and TME was finished with the assistance of robot (da Vinci Xi surgical system) | Procedure: Robotic-assisted total mesorectal excision<br>* TME will be performed with the assistance of robot in rectal cancer<br>|
| Other: LATME<br>In LaTME groups, the low anterior resection and mesorectal excision procedures was completed under laparoscopy. | Procedure: laparoscopic-assisted total mesorectal excision<br>* TME will be performed with the assistance of laparoscopy in rectal cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intersphincteric resection (ISR) | The primary outcome is the incidence of ISR. ISR is defined according to the definition by a Japanese study group. When the distal resection margin is from dentate line to the intersphincteric groove, ISR will be recorded.The distal resection line of the internal anal sphincter was at the intersphincteric groove in total ISR, between the dentate line and the intersphincteric groove in subtotal ISR and at the dentate line in partial ISR | during the operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| coloanal anastomosis (CAA) | CAA was defined as the anastomosis of distal colon and surgical anal canal. In CAA anastomosis, the distal resection margin is below the upper level of the levator ani muscle. Conversion to open was defined as an abdominal incision larger than necessary for specimen retrieval. | during the operation | 
| conversion to open | Conversion to open surgery was defined as an abdominal incision larger than necessary for specimen retrieval extraction. | during the operation | 
| conversion to transanal TME (TaTME) | Conversion to TaTME was defined as TME that cannot be finished via transabdominal approach, and have to be finished by transanal approach with the help of imaging system and endoscopic instruments. It should be noted that if TME was completely done via transabdominal approach, simply dissecting the internal sphincter and intersphincteric space or finish the coloanal anastomosis via transanal approach were not classified as TaTME | during the operation | 
| 30-day postoperative morbidity | The 30-day morbidity is defined as intraoperative adverse events and postoperative complications within 30 days. The intraoperative adverse events include intraoperative bleeding (>200 ml), pelvic vascular and nerve injury, vascular injury in other parts, digestive tract injury, ureteral injury, and anastomotic defect. Furthermore, the 30-day postoperative complications are evaluated according to Clavien-Dindo classification | within 30 days after operation | 
| 30-day postoperative mortality | The 30-day mortality is defined as death within 30 day after operation | within 30 days after operation | 
| 3-year disease-free survival (DFS) | DFS is defined as the time from randomization to the discovery of local recurrence, distant metastasis, or death of the tumor | 3 years after operation | 
| 3-year local recurrence rate (LR) | LR is defined as tumor recurrence (evaluated by positron emission tomography, computed tomography, or magnetic resistance) that occurs in the pelvic cavity, perineal area, root of inferior mesenteric artery, descending colon, and sigmoid mesenteric area, and is confirmed through pathological biopsy or reoperation. | 3 years after operation | 
| 3-year overall survival (OS) | OS is defined as the time from randomization to death due to any cause. | 3 years after operation | 
| distance to distal resection margin (DRM) | The distance to the DRM is defined as the shortest length between the tumor and the DRM. DRM positivity is defined as a distal margin within 1 mm of the tumor. | within 30 days after operation | 
| distance to circumferential resection margin (CRM) | The distance to the CRM is defined as the shortest length between the tumor and the CRM. CRM positivity is defined as tumor cells within 1 mm from the CRM by microscopy | within 30 days after operation | 
| 3-year urinary function | Urinary function will be evaluated by International consultation on incontinence questionnaire short form (ICIQ-SF). The patients will be asked to complete ICIQ-SF every 3 months in the first year after operation, and every 6 months after the first year follow-up, until we finished the 3-year follow-up. | 3 years after operation | 
| The proportion of patients receiving abdominoperineal resection | the proportion of patients receiving abdominoperineal resection | during the operation | 
| 3-year quality of life | Quality of life will be evaluated by EORTC quality of life questionnaire-core 30 (QLQ-C30) form. The patients will be asked to complete QLQ-C30 every 3 months in the first year after operation, and every 6 months after the first year follow-up, until we finished the 3-year follow-up. | 3 years after operation | 
| 3-year sexual function | Sexual function of male will be evaluated by International Index of Erectile Function (IIEF-5). Sexual function of female will be evaluated by Female Sexual Function Index (FSFI). Evaluation will be performed every 3 months in the first year after operation, and every 6 months after the first year follow-up, until we finished the 3-year follow-up. | 3 years after operation | 
| 3-year defecation function | Defecation function will be evaluated by low anterior resection syndrome (LARS) form. The patients will be asked to complete LARS form every 3 months in the first year after operation, and every 6 months after the first year follow-up, until we finished the 3-year follow-up. | 3 years after operation |