Transanal Versus Laparoscopic Total Mesorectal Excision For Rectal Cancer

• ClinicalTrials.gov Identifier: NCT02966483
• Recruitment Status: Recruiting
• First Posted: November 17, 2016
• Last Update Posted: November 7, 2022
• Sponsor: Sun Yat-sen University
• Collaborators: Peking Union Medical College Hospital; The First Hospital of Jilin University; RenJi Hospital; Shengjing Hospital; The Second People's Hospital of Yibin; Daping Hospital and the Research Institute of Surgery of the Third Military Medical University; Nanchong Central Hospital; Zunyi Medical College; The First Affiliated Hospital of University of South China; Xinqiao Hospital; Nanfang Hospital, Southern Medical University; First Affiliated Hospital Xi'an Jiaotong University; Ruijin Hospital; Affiliated Hospital of Guangdong Medical University; The Third Xiangya Hospital of Central South University
• Information provided by (Responsible Party): Yanhong Deng, Sun Yat-sen University

Tracking Information

• First Submitted Date: November 8, 2016
• First Posted Date: November 17, 2016
• Last Update Posted Date: November 7, 2022
• Actual Study Start Date: April 2016
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 27, 2021)

• Disease-free survival [ Time Frame: 3 years ]
  Disease-free survival
• Overall survival [ Time Frame: 5 years ]
  Overall survival

• Original Primary Outcome Measures (submitted: November 16, 2016): Disease-free survival [ Time Frame: 3 years ]

Current Secondary Outcome Measures (submitted: May 27, 2021)

• Positive circumferential resection margin (CRM) [ Time Frame: 3 years ]
  Involved CRM (tumor cells <1mm)
• Overall survival [ Time Frame: 10 years ]
  Overall survival
• Mesorectal completeness [ Time Frame: 3 years ]
  The quality of the mesorectum or TME specimen (complete;nearly complete; incomplete)
• Number of retrieved lymph nodes [ Time Frame: 3 years ]
  Number of retrieved lymph nodes
• Morbidity rate [ Time Frame: 1 years ]
  Morbidity rate
• Mortality rate [ Time Frame: 1 years ]
  Mortality rate
• Anorectal function outcomes [ Time Frame: 3 years ]
  To evaluate defecating function with Wexner score
• Sexual functional outcomes [ Time Frame: 3 years ]
  To evaluate sexual function with IIEF(International Index of Erectile Function) questionnaire
• The patient's Quality of life: EORTC QLQ-30 questionnaire [ Time Frame: 3 years ]
  To evaluate quality of life with EORTC QLQ-30 questionnaire

Original Secondary Outcome Measures (submitted: November 16, 2016)

• Overall survival [ Time Frame: 5 years ]
• Positive circumferential resection margin (CRM) [ Time Frame: 3 years ]
  Involved CRM (tumor cells <1mm)
• Mesorectal completeness [ Time Frame: 3 years ]
  The quality of the mesorectum or TME specimen (complete;nearly complete;imcomplete)
• Number of retrieved lymph nodes [ Time Frame: 3 years ]
• Morbidity rate [ Time Frame: 1 years ]
• Mortality rate [ Time Frame: 1 years ]
• Anorectal function outcomes [ Time Frame: 3 years ]
  To evaluate defecating function with Wexner score
• Sexual functional outcomes [ Time Frame: 3 years ]
  To evaluate sexual function with IIEF(International Index of Erectile Function) questionnaire
• Quality of life [ Time Frame: 3 years ]
  To evaluate quality of life with EORTC QLQ-30 questionnaire

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Transanal Versus Laparoscopic Total Mesorectal Excision For Rectal Cancer
• Official Title: Transanal Versus Laparoscopic Total Mesorectal Excision For Mid And Low Rectal Cancer (TaLaR): A Multicentre Randomised Clinical Trial
• Brief Summary: Laparoscopic surgery for rectal cancer has been successfully proven to be a non-inferior alternative regarding resection quality, and oncological outcomes of patients as compared to open surgery in mangy clinical trails. Moreover, laparoscopic surgery is advantageous over open surgery with regard to operative invasiveness, patient's recovery, and wound related complications. Thus, laparoscopic surgery has gained great popularity over the past decades. However, specifically for mid and low rectal cancer, laparoscopic surgery is technically demanding, which sometimes leads to high morbidity and unsatisfactory resection quality, especially in challenging cases such as bulky mesorectum, enlarged prostate, irradiated pelvis, etc. Under this circumstance, transanal total mesorectal excision (TaTME) , the so called "down-to-up" alternative, has emerged as a promising solution to these problems in recent years and more and more small studies have proven the feasibility and advantages of this technique, making it become a hot topic among both literature and conferences. However, TaTME is still at early birth, higher-level evidences, either multicentric, or comparative study with conventional surgery is strikingly lacking. Thus the investigators conduct this multicentre randomised clinical trial, comparing transanal TME versus laparoscopic TME for mid and low rectal cancer, aiming to prove the hypothesis that TaTME may achieve better resection quality and result in non-inferior oncological outcome, as well as short term operative morbidity and mortality.

Detailed Description

Background:In recent years, transanal mesorectal excision (TaTME) has emerged as a promising surgical alternative for rectal cancer, especially for mid and low rectal cancer. Theoretically, TaTME holds the potential advantage of providing better access to mobilize the distal rectum, and thus could achieve better pathologic outcomes, such as lower involved circumferential margin (CRM) and incomplete resected mesorectum, which could translate into better oncological outcome for the patients in the long term. However, until now, the feasibility and the non-inferiority (compared with laparoscopic total mesorectal excision, LpTME) of this technique has only been validated in studies with limitations of small sample size, retrospective nature.

Study Objective:This study aims to evaluate the TaTME technique compared with conventional laparoscopic rectal surgery, focusing on resection quality, as well as long-term survival results.

Study design This study is a prospective, multi-center, randomized, open-label, parallel group trial. The randomisation ratio of TaTME over LpTME will be 1:1. A central electronic data capture (EDC) system will be utilized for randomization, electronic CRF and data collection. All comparative analyses will be conducted on an "intention to treat" basis.

Sample size: Sample-size calculation of this trial based on 3-year DFS and 5-year OS; but the sample size according to 5-year OS was larger than that based on 3-year DFS. The expected 5-year OS among clinical stage I-III rectal cancer patients treated with laTME was 77·4%. Allowing a difference of 10% as the non-inferiority margin, 910 patients would be required to sufficiently declare taTME noninferior to laTME in 5-year OS based on a log-rank test with an α error of 2·5% (in a two-sided test) and power of 80%. Assuming a dropout rate of 20%, a total of 1114 patients were planned to enroll for this trial.

Study Endpoints:The primary end point of this study is 3-year disease-free survival (DFS) rate and a 5-year overall survival (OS) rate. Secondary endpoints include: 1) resection quality, mainly including circumferential involvement rate, and completeness of mesorectum. Resected specimen was pathologically processed and assessed at each center by trained and qualified pathologists independently.2)short term operative results such as morbidity and mortality, etc.; 3) long term oncological outcome such as local recurrence, and overall survival. Besides, functional outcome and quality of life are also evaluated.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Transanal or Laparoscopic Total Mesorectal Excision treat rectal cancer

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Rectal Neoplasms Malignant
• Surgery

Intervention

• Procedure: TaTME
  Transanal Total Mesorectal Excision
  Other Name: Transanal TME
• Procedure: LpTME
  Conventional Laparoscopic Total Mesorectal Excision
  Other Name: Laparoscopic TME

Study Arms

• Experimental: Transanal Total Mesorectal Excision
  The rectum is mobilized and resected transanally (from bottom to up) according to TME principles, via transanal platform (either rigid or flexible platform).An ideal TaTME is defined as the extraperitoneal portion of the rectum being mobilized from below.
  Intervention: Procedure: TaTME
• Active Comparator: Laparoscopic Total Mesorectal Excision
  The traditional laparoscopic TME (LpTME) was performed via standard laparoscopic techniques, including multiple trocars and conventional laparoscopic instruments.
  Intervention: Procedure: LpTME

Publications *

• Chen WH, Kang L, Luo SL, Zhang XW, Huang Y, Liu ZH, Wang JP. Transanal total mesorectal excision assisted by single-port laparoscopic surgery for low rectal cancer. Tech Coloproctol. 2015 Sep;19(9):527-34. doi: 10.1007/s10151-015-1342-1. Epub 2015 Jul 29.
• Kang L, Chen WH, Luo SL, Luo YX, Liu ZH, Huang MJ, Wang JP. Transanal total mesorectal excision for rectal cancer: a preliminary report. Surg Endosc. 2016 Jun;30(6):2552-62. doi: 10.1007/s00464-015-4521-2. Epub 2015 Aug 27.
• Zeng Z, Luo S, Chen J, Cai Y, Zhang X, Kang L. Comparison of pathological outcomes after transanal versus laparoscopic total mesorectal excision: a prospective study using data from randomized control trial. Surg Endosc. 2020 Sep;34(9):3956-3962. doi: 10.1007/s00464-019-07167-1. Epub 2019 Oct 4.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 16, 2016): 1114
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

histologically proven rectal adenocarcinoma;

tumor located below the level of peritoneal reflection ;

diagnosis of rectal cancer amenable to curative surgery;

no evidence of distant metastases;

preoperative tumor stage within III;

no threaten mesorectal fascia (MRF)after neoadjuvant therapy;

no contraindication to laparoscopic surgery;

without history of other malignancies;

Written informed consent

Exclusion Criteria:

could not perform sphincter preservation surgery (requiring a Mile's procedure);

T4b tumor invading adjacent organs;

T1 tumors that can be locally resected

should take neoadjuvant therapy but refuse it;

recurrent cancer;

concurrent or previous diagnosis of invasive cancer within 5 years;

emergent surgery with intestinal obstruction or perforation;

history of colorectal surgery;

fecal incontinence;

history of inflammatory bowel disease;

with contraindications to general anaesthesia(ASA class 4 or 5);

pregnant or breast-feeding;

history of mental disorder

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Liang Kang, MD,PHD; 008613602886833; eonkang@163.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02966483
• Other Study ID Numbers: SYSU-RECTAl-2016
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Yanhong Deng, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Sun Yat-sen University
• Original Study Sponsor: Same as current

Collaborators

• Peking Union Medical College Hospital
• The First Hospital of Jilin University
• RenJi Hospital
• Shengjing Hospital
• The Second People's Hospital of Yibin
• Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
• Nanchong Central Hospital
• Zunyi Medical College
• The First Affiliated Hospital of University of South China
• Xinqiao Hospital
• Nanfang Hospital, Southern Medical University
• First Affiliated Hospital Xi'an Jiaotong University
• Ruijin Hospital
• Affiliated Hospital of Guangdong Medical University
• The Third Xiangya Hospital of Central South University

Investigators

• Principal Investigator: Jianping Wang, MD,PHD; The Sixth Affiliated Hospital, Sun Yat-sen University

• PRS Account: Sun Yat-sen University
• Verification Date: November 2022