Preservation Vs. Dissection of No. 253 Lymph Nodes of Robotic Resection for Mid/Low Rectal Cancer (REAL2)

Preservation Versus Dissection of Inferior Mesenteric Artery Lymph Nodes of Robotic Radical Resection for Mid/Low Rectal Cancer (REAL2): A Multicenter Randomized Controlled Trial

In this study, patients with middle or low rectal cancer will receive robotic radical resection, and will be randomly assigned to receive inferior mesenteric artery lymph nodes dissection or preservation. The 3-year disease-free survival rates of these two surgical approaches will be compared.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: Preservation of Inferior Mesenteric Artery Root Lymph Node; Procedure: Dissection of Inferior Mesenteric Artery Root Lymph Node

Detailed Description

The goal of this clinical trial is to compare the outcomes of preserving versus dissecting inferior mesenteric artery root lymph nodes (IMA-LN) during robotic radical resection for mid/low rectal cancer. It aims to evaluate both short-term safety and long-term efficacy. The main questions it seeks to answer are:

1. Does preserving IMA-LN achieve non-inferior 3-year disease-free survival (DFS) compared to IMA-LN dissection?
2. Does preserving IMA-LN reduce postoperative complications (e.g., anastomotic leakage, urinary/defecation dysfunction) and improve quality of life?

Researchers will compare two surgical strategies:

1. IMA-LN preservation group: No dissection of IMA root lymph nodes, with ligation of the inferior mesenteric artery (IMA) distal to the left colic artery.
2. IMA-LN dissection group: Complete dissection of IMA root lymph nodes, with high or low ligation of the IMA.

Both groups will undergo robotic surgery following total mesorectal excision (TME) principles.

Participants will:

1. Be randomly assigned to either the preservation or dissection group. Receive standardized preoperative evaluations (imaging, biopsies) and postoperative follow-up for 3 years.
2. Undergo regular clinical assessments, including tumor marker tests, imaging (CT/MRI), colonoscopy, and quality-of-life questionnaires (evaluating urinary/sexual/defecation function).
3. Have surgical outcomes (e.g., complications, lymph node counts) and survival data recorded.

The trial aims to provide high-level evidence for optimizing surgical strategies in mid/low rectal cancer treatment.

• Study Type: Interventional
• Enrollment (Estimated): 1596
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianmin Xu, Prof.; Phone Number: +86 13501984869; Email: xujmin@aliyun.com
• Study Contact Backup: Name: Qingyang Feng, M.D.; Phone Number: 86-021-64041990; Email: fqy198921@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
      • Contact: Jianmin Xu, Prof.; Phone Number: +86-021-64041990; Email: xujmin@aliyun.com
      • Contact: Qingyang Feng, Dr.; Phone Number: +86-021-64041990; Email: fqy198921@163.com
      • Principal Investigator: Jianmin Xu, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years and ≤80 years
2. Pathologically confirmed rectal adenocarcinoma by colonoscopic biopsy
3. Tumor located ≤10 cm from the anal verge
4. No metastasis at the root of the inferior mesenteric artery (IMA) and no lateral lymph node metastasis confirmed by pelvic ultrasound, contrast-enhanced CT, and/or PET-CT (diagnostic criteria per the 2024 Chinese Society of Clinical Oncology [CSCO] Guidelines)
5. No distant metastasis (including pelvic, peritoneal, hepatic, pulmonary, cerebral, skeletal, or distant lymph node metastasis) confirmed by imaging
6. Pelvic MRI and/or transrectal ultrasound confirming cT1-T3 N0-1 stage, or ycT1-T3 Nx after neoadjuvant therapy (radiotherapy, chemotherapy, immunotherapy, targeted therapy)
7. No history of other malignancies (except adequately treated basal cell carcinoma or cervical carcinoma in situ)
8. Suitable for robotic surgery
9. Signed informed consent

Exclusion Criteria:

1. Clinical complete response after radiotherapy, chemotherapy, immunotherapy, or targeted therapy
2. cT1N0 tumors suitable for local excision
3. Emergency surgery required due to acute bowel obstruction, hemorrhage, or perforation
4. Multiple primary colorectal malignancies
5. Familial adenomatous polyposis (FAP), Lynch syndrome, or inflammatory bowel disease
6. Concomitant conditions requiring concurrent colonic resection
7. American Society of Anesthesiologists (ASA) grade >III
8. Pregnancy or lactation
9. Preoperative short-course radiotherapy
10. Inability of the patient/family to comprehend the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IMA-LN Preservation; Patients underwent robotic radical resection for rectal cancer, adhering to the principles of Total Mesorectal Excision (TME) or Tumor-Specific Mesorectal Excision (TSME), but preserving the lymph nodes at the root of the inferior mesenteric artery (IMA).	Procedure: Preservation of Inferior Mesenteric Artery Root Lymph Node; Patients underwent robotic radical resection for rectal cancer, adhering to the principles of Total Mesorectal Excision (TME) or Tumor-Specific Mesorectal Excision (TSME), but preserving the lymph nodes at the root of the inferior mesenteric artery (IMA).; Other Names: IMA-LN Preservation
Placebo Comparator: IMA-LN Dissection; Patients underwent robotic radical resection for rectal cancer, adhering to the principles of Total Mesorectal Excision (TME) or Tumor-Specific Mesorectal Excision (TSME), and dissecting the lymph nodes at the root of the inferior mesenteric artery (IMA).	Procedure: Dissection of Inferior Mesenteric Artery Root Lymph Node; Patients underwent robotic radical resection for rectal cancer, adhering to the principles of Total Mesorectal Excision (TME) or Tumor-Specific Mesorectal Excision (TSME), and dissecting the lymph nodes at the root of the inferior mesenteric artery (IMA).; Other Names: IMA-LN Dissection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year disease-free survival rate	The 3-year disease-free survival (DFS) rate was defined as the percentage of patients with no death and no locoregional recurrence and no distant metastases within 3 years postoperatively, assessed via imaging (contrast-enhanced CT/MRI, PET-CT) or histopathological confirmation (colonoscopy/biopsy).	3 years after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day postoperative complication rate	The rate of patients with any of postoperative complications (Clavien-Dindo grade II or higher grade) within 30 days after surgery	30 days after surgery
Urinary function	Urinary function will be assessed using the International Prostate Symptom Score (IPSS) scale before surgery, at 3 months, 6 months and 1 year after surgery. For IPSS, the range of the score is 0 to 35, with higher scores indicating worse function.	1 year after surgery
Male sexual function	Male sexual function will be assessed using the International Index of Erectile Function-5 (IIEF-5) scale before surgery, at 3 months, 6 months and 1 year after surgery. For IIEF-5, the range of the score is 1 to 25, with lower scores indicating worse function.	1 year after surgery
Female sexual function	Female sexual function will be assessed using the Female Sexual Function Index (FSFI) scale before surgery, at 3 months, 6 months and 1 year after surgery. For FSFI, the range of the score is 2 to 36, with lower scores indicating worse function.	1 year after surgery
Defecation function	Defecation function will be assessed using the Wexner Continence Grading Scale before surgery, at 3 months, 6 months and 1 year after surgery. For the Wexner scale, the range of the score is 0 to 20, with higher scores indicating worse function.	1 year after surgery
3-year locoregional recurrence rate	The 3-year locoregional recurrence (LRR) rate was defined as the percentage of patients with any locoregional recurrence within 3 years postoperatively, assessed via imaging (contrast-enhanced CT/MRI, PET-CT) or histopathological confirmation (colonoscopy/biopsy).	3 years after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative complication rate	Percentage of patients with any of intraoperative complications, such as: organ/structural injury (any injury requiring additional surgical repair), device malfunction (leading to procedural delay >30 minutes), fecal contamination (compromising the sterile surgical field), iatrogenic perforation (tumor or adjacent tissue perforation caused by manipulation), anastomotic complications (intraoperative anastomotic failure/leak requiring repair), tumor residual (tumor not radically resected), major hemorrhage (blood loss >200 ml at one surgical site), cardiac events (requiring intraoperative intervention), respiratory events (requiring intraoperative intervention).	30 days after surgery
Open conversion rate	Percentage of patients converting to open surgery.	30 days after surgery
Operative time	Time from skin incision to wound closure, recorded in minutes.	30 days after surgery
Estimated intraoperative blood loss	Calculated as suctioned blood volume + gauze weight change, recorded in ml.	30 days after surgery
Blood transfusion rate	Percentage of patients with any of transfusion intraoperative or within 30 days postoperatively.	30 days after surgery
Protective stoma rate	Percentage of patients with any of protective stoma, including terminal ileostomy or colostomy.	30 days after surgery
Macroscopic completeness of resection	Percentage of classification as complete, near-complete, or incomplete, according to previous report (Nagtegaal ID, et al. J Clin Oncol 2002; 20: 1729-34.)	30 days after surgery
Proximal resection margin distance	Distance from tumor upper edge to proximal resection margin, recorded in cm.	30 days after surgery
Distal resection margin distance	Distance from tumor lower edge to distal resection margin (excludes abdominoperineal resection), recorded in cm.	30 days after surgery
Distal resection margin positivity rate	Percentage of patients with positive distal resection margin (excluding abdominoperineal resection).	30 days after surgery
Circumferential resection margin positivity rate	Percentage of patients with circumferential resection margin ≤1 mm.	30 days after surgery
Number of lymph nodes harvested	Total number of lymph nodes detected from the specimen.	30 days after surgery
Number of No.253 lymph nodes harvested	Number of No. 253 lymph nodes detected at the root of inferior mesenteric artery from the specimen.	30 days after surgery
Number of positive lymph nodes	Number of positive lymph nodes detected from the specimen.	30 days after surgery
Number of positive No. 253 lymph nodes	Number of positive No. 253 lymph nodes detected at the root of inferior mesenteric artery from the specimen.	30 days after surgery
Postoperative mortality rate	Percentage of patients died within 30 days postoperatively.	30 days after surgery
30-day readmission rate	Percentage of patients with rehospitalization for disease-related causes within 30 days postoperatively.	30 days after surgery
30-day reoperation rate	Percentage of patients with unplanned surgery for disease-related causes within 30 days postoperatively.	30 days after surgery
Time to first flatus	Time from surgery completion to first passage of gas/stoma bag inflation, recorded in hour.	30 days after surgery
Time to first liquid diet	Time from surgery completion to first liquid intake, recorded in hour.	30 days after surgery
Time to first semi-solid diet	Time from surgery completion to first semi-solid intake, recorded in hour.	30 days after surgery
Time to first defecation	Time from surgery completion to first bowel movement, recorded in hour.	30 days after surgery
Time to first autonomous urination	Time from surgery completion to first autonomous urination, recorded in hour.	30 days after surgery
Postoperative hospital stay	Time from surgery completion to discharge, including readmissions within 30 days postoperatively, recorded in day.	30 days after surgery
3-year overall survival rate	The 3-year overall survival (OS) rate was defined as the percentage of patients with no death within 3 years postoperatively.	3 years after surgery

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Study Chair: Jianmin Xu, Prof., Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: April 25, 2025
• First Posted (Actual): May 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: lymph node dissection; Robotic Surgery; disease-free survival; No. 253 lymph node
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: REAL2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

During the recruitment process, investigators will directly contact enrolled patients to avoid privacy breaches. All identity-related data will be stored separately in locked systems and de-identified. All researchers must refrain from disclosing patients' identifiable information.

De-identified patient data will be accessible to all investigators in this study and may be used for meta-analysis after audit and validation. Researchers should contact the principal investigator, Professor Jianmin Xu (xujmin@aliyun.com), to request data by providing a research proposal and institutional credentials. Requests will be reviewed and approved by the REAL2 trial's Independent Review Committee. Data will be available from the publication date until 36 months post-publication.

• IPD Sharing Time Frame: Data will be available from the publication date until 36 months post-publication.
• IPD Sharing Access Criteria: De-identified patient data will be accessible to all investigators in this study and may be used for meta-analysis after audit and validation. Researchers should contact the principal investigator, Professor Jianmin Xu (xujmin@aliyun.com), to request data by providing a research proposal and institutional credentials.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No