Proximally Extended Resection for Rectal Cancer After Neoadjuvant Chemoradiotherapy (PERN)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: Conventional resection; Procedure: Proximally extended resection

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qiyuan Qin, M.D.; Phone Number: 86-20-38254052; Email: qinqy3@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sixth Affiliated Hospital, Sun Yat-sen University
      • Contact: Qiyuan Qin, M.D.; Phone Number: 86-20-38254052; Email: qinqy3@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional Resection; 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; 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.
Experimental: Proximally Extended Resection; 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; 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.

What is the study measuring?

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
3-year disease free survival		3 years
5-year overall survival		5 years
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
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

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of major bowel dysfunction in patients with tumor of different location	at the time of 12 months after the restoration of defunctioning stoma
Incidence of major bowel dysfunction in patients with tumor of different location	at the time of 36 months after the restoration of defunctioning stoma
Incidence of major bowel dysfunction in patients with tumor of different location	at the time of 60 months after the restoration of defunctioning stoma
Incidence of anastomotic complication in patients with tumor of different location	up to 12 months postoperatively
Operative duration by minutes	at the time of surgery
Intraoperative blood loss by millilitres	at the time of surgery
Postoperative rehabilitation time	up to 1 months postoperatively
Postoperative hospital stay by days	up to 1 months postoperatively

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Collaborators: Peking Union Medical College Hospital; Shanghai Changzheng Hospital
• Investigators: Study Director: Lei Wang, MD, PhD, Sixth Affiliated Hospital, Sun Yat-sen University; Principal Investigator: Hui Wang, M.D., Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 5, 2016
• First Submitted That Met QC Criteria: January 5, 2016
• First Posted (Estimated): January 7, 2016

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Rectal cancer; Neoadjuvant therapy; Chemoradiotherapy; Bowel function; Anastomosis; Resection margin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: PERN2015019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No