Proximally Extended Resection for Rectal Cancer After Neoadjuvant Chemoradiotherapy

Study Overview
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Brief Summary
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Neoadjuvant chemoradiotherapy has been recommended as the standard preoperative treatment for locally advanced rectal cancer. However, preoperative radiotherapy increases the risk of bowel dysfunction after sphincter-preserving surgery, for which patients suffer from incontinence, urgency, and unpredictability defecation problems. Furthermore, preoperative chemoradiotherapy is a potential risk factor of anastomotic leakage and stenosis after rectal cancer surgery. Unhealthy anastomosis, with both ends of injured bowel segments after pelvic radiation, is a major concern. When conventional surgical procedures would retain part of sigmoid colon that has been included in the radiation target, sphincter-preserving surgery with proximally extended resection margin could provide an intact proximal colon limb for the anastomosis. It is not known yet whether proximally extended resection improves postoperative bowel function or anastomotic integrity for patients with rectal cancer after neoadjuvant chemoradiotherapy. The proposed study will compare sphincter-preserving surgery with and without proximally extended resection margin, to observe the postoperative bowel function, as well as the incidence of anastomotic complication. This study will examine a new surgical strategy, which potentially benefits the patients undergoing neoadjuvant chemoradiotherapy.

Official Title
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Randomized Trial of Sphincter-Preserving Surgery With Proximally Extended Resection Margin on Bowel Function and Anastomotic Complication for Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy

Conditions
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Rectal Cancer

Intervention / Treatment
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* Procedure: Conventional resection
* Procedure: Proximally extended resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-75 years old ECOG performance status: 0-2 Histologically confirmed adenocarcinoma of the rectum Distal border of the tumor located ≤ 12 cm from the anal verge Primary stage T3-4 or any node-positive disease Undergoing long-course 5-fluorouracil based neoadjuvant chemoradiotherapy Conventional fractionated radiotherapy of at least 45 Gy Resectable disease after neoadjuvant chemoradiotherapy No evidence of distant metastasis Amenable to sphincter-preserving surgery Tolerable to general anesthesia Provision of written informed consent Exclusion Criteria: Prior or concurrent malignancies within the past 5 years except for effectively treated squamous cell or basal cell skin cancer, melanoma in situ, or carcinoma in situ of the cervix Synchronous colon cancer History of colorectal resection except appendectomy Acute intestinal obstruction or perforation Multiple visceral resection Abdominoperineal resection American Society of Anesthesiologists (ASA) class Ⅳ or Ⅴ Pregnant or nursing, fertile patients do not use effective contraception Serious cardiovascular disease, uncontrolled infections, or other serious uncontrolled concomitant disease Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional Resection<br>Patients receive conventional resection with standard proximal excision margin. The sigmoid colon is anastomosed to the rectum or anus. A defunctioning ileostomy is routinely performed. | Procedure: Conventional resection<br>* The conventional technique requests an excision of at least 10 cm of bowel proximal to the tumor, and the sigmoid colon is anastomosed to the rectum or anus. A defunctioning ileostomy is routinely performed.<br>|
| Experimental: Proximally Extended Resection<br>Patients receive proximally extended resection. The whole sigmoid colon and rectum proximal to the tumor is removed, and the descending colon is anastomosed to the rectum or anus. A defunctioning ileostomy is routinely performed. | Procedure: Proximally extended resection<br>* The modified technique requests an excision of the whole sigmoid colon and rectum proximal to the tumor, and the descending colon is anastomosed to the rectum or anus. A defunctioning ileostomy is routinely performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of major bowel dysfunction | Low anterior resection syndrome score (LARS score) will be used to assess the bowel function. Number of participants with major LARS will be calculated for the incidence of major bowel dysfunction. | at the time of 12 months after the restoration of defunctioning stoma | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anastomotic leakage |  | up to 6 months postoperatively | 
| Incidence of anastomotic stenosis |  | 12 months postoperatively | 
| Incidence of major bowel dysfunction | Low anterior resection syndrome score (LARS score) will be used to assess the bowel function. | at the time of 36 months after the restoration of defunctioning stoma | 
| Incidence of major bowel dysfunction | Low anterior resection syndrome score (LARS score) will be used to assess the bowel function. | at the time of 60 months after the restoration of defunctioning stoma | 
| 3-year disease free survival |  | 3 years | 
| 5-year overall survival |  | 5 years | 
| Incidence of anastomotic haemorrhage |  | up to 1 month postoperatively | 
| Incidence of intraoperative complication |  | at the time of surgery | 
| Postoperative morbidity |  | up to 30 days postoperatively | 
| Postoperative mortality |  | up to 30 days postoperatively | 
| Quality of life impairment | Quality of life will be assessed by EORTC QLQ-C30 and EORTC QLQ-CR29. | at the time of 12 months after the restoration of defunctioning stoma | 
| Quality of life impairment | Quality of life will be assessed by EORTC QLQ-C30 and EORTC QLQ-CR29. | at the time of 36 months after the restoration of defunctioning stoma | 
| Quality of life impairment | Quality of life will be assessed by EORTC QLQ-C30 and EORTC QLQ-CR29. | at the time of 60 months after the restoration of defunctioning stoma | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal cancer, Neoadjuvant therapy, Chemoradiotherapy, Resection margin, Bowel function, Anastomosis