Locally Advanced Rectal Carcinoma
Conditions
Brief summary
The goal of this clinical trial is to learn evaluate the safety and efficacy of reduced surgical resection margins in patients with local advanced upper rectal or rectosigmoid junction tumors who met the ycT≤3N0M0 regression following neoadjuvant therapy. The main questions it aims to answer are: Does reduced surgical resection margins (3 cm of distal margin and 5 cm of proximal margin) meet the radical resection criteria, including the rate of negative resection margin, the number of lymph node harvested? How is the surgical safety of reduced surgical resection, including the surgical duration , bleeding, recovery time and postoperative complications? Is reduced surgical margins resection (3 cm of distal margin and 5 cm of proximal margin) inferior to conventional surgical margins resection (5 cm of distal margin and 10 cm of proximal margin) in terms of oncology safety?
Detailed description
This study will be a prospective, multicenter, randomized phase III controlled trial conducted in collaboration with Sun Yat-sen University Sixth Affiliated Hospital and multiple domestic colorectal cancer centers. It will involve patients with upper rectal or rectosigmoid junction tumors at a clinical stage of cT3-4N+M0. The trial will compare conventional resection margins (distal 5 cm + proximal 10 cm) with reduced margins (distal 3 cm + proximal 5 cm) in patients who have met the ycT ≤3N0M0 regression criteria following neoadjuvant therapy or total neoadjuvant therapy (TNT). The aim is to evaluate the safety and efficacy of reduced surgical resection margins. The primary research objective is 3-year disease-free survival (DFS). The secondary research objectives includes radical surgery outcomes (R0 resection rate and number of lymph nodes dissected), surgical safety metrics (Operation time, intraoperative blood loss, incidence of anastomotic complications, etc.) and other survival outcomes (1-year disease-free survival and overall survival).
Interventions
PROCEDURELaparoscopic resection
Laparoscopic resection of bowel and corresponding mesentery.
OTHERNeoadjuvant Therapy
Neoadjuvant Therapy aims to downstage the tumor including different chemotherapy, targeted therapy and immunotherapy.
Sponsors
Sixth Affiliated Hospital, Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years. 2. Histopathologically confirmed adenocarcinoma of the rectum or rectosigmoid junction. 3. Clinical stage cT3-4N+M0, with or without positive mesorectal fascia (MRF), with or without extramural vascular invasion (EMVI); Tumor location confirmed by imaging to be above the peritoneal reflection and by endoscopy to be in the upper rectum or rectosigmoid junction. 4. For patients with pMMR (proficient Mismatch Repair; immunohistochemistry shows expression of all four proteins: MSH1, MSH2, MSH6, PMS2) or MSS (Microsatellite Stable) status: Tumor downstaged to T≤3N0M0 after neoadjuvant chemotherapy or total neoadjuvant therapy (TNT). Chemotherapy regimens include, but are not limited to, FOLFOX6, CAPOX, or FOLFOXIRI. 5. For patients with dMMR (deficient Mismatch Repair; immunohistochemistry shows loss of expression in two or more of MSH1, MSH2, MSH6, PMS2) or MSI-H (Microsatellite Instability-High) status: Tumor downstaged to T≤3N0M0 after immunotherapy. 6. Pre-neoadjuvant therapy / Preoperative staging methods: All patients underwent contrast-enhanced CT for staging. Peri-rectal metastatic lymph nodes: defined as nodes with short-axis diameter ≥10 mm or exhibiting CT characteristics typical of metastasis. Preoperative chest, abdominal CT, and pelvic MRI ruling out distant metastasis. 7. No signs of bowel obstruction; OR bowel obstruction that has resolved following proximal diverting colostomy. 8. No prior colorectal surgery. 9. No prior chemotherapy or radiotherapy. 10. No prior treatment with biologic agents (e.g., monoclonal antibodies), immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies), or other investigational drugs. 11. Prior endocrine therapy: Allowed. 12. Signed informed consent form.
Exclusion criteria
1. History of malignant colorectal tumor(s). 2. Requiring emergent surgery (e.g., due to bowel obstruction or intestinal hemorrhage). 3. Primary tumor invading adjacent organs/tissues precluding R0 resection. 4. Multifocal primary tumors. 5. Concurrent diagnosis of other active malignancy. 6. Participation in other clinical trials within 4 weeks prior to enrollment or current participation. 7. ASA physical status classification ≥ IV and/or ECOG performance status ≥ 2 (see Appendix for details). 8. Severe hepatic, renal, cardiopulmonary, or coagulation dysfunction, or significant comorbidities contraindicating surgery. 9. History of severe psychiatric disorders. 10. Pregnancy or lactation. 11. Uncontrolled preoperative infection. 12. Other clinical or laboratory conditions deemed by the investigator to render the patient unsuitable for the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3 years DFS | 3 year | 3 years Disease Free Survival Rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of lymph node harvested | 1 year | Number of lymph node harvested in participants |
| Surgical duration | 1 year | Operative time in participants |
| Intraoperative blood loss | 1 year | Blood loss during the operation |
| R0 resection rate | 1 year | R0 resection rate in participants |
| 1 year DFS | 1 year | 1 year Disease Free Survival Rate |
| 3 years OS | 3 year | 3 years Overall Survival Rate |
| Anastomotic leakage | 1 year | Post-operative leakage in anastomotic site |
Countries
China
Outcome results
None listed