Clinical trial NCT02966483: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Neoplasms Malignant
Surgery
Keywords: Rectal cancer
Laparoscopic surgery
Total mesorectal excision
Transanal
Multicentre randomised clinical trial
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
name: The First Hospital of Jilin University
name: RenJi Hospital
name: Shengjing Hospital
name: The Second People's Hospital of Yibin
name: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
name: Nanchong Central Hospital
name: Zunyi Medical College
name: The First Affiliated Hospital of University of South China
name: Xinqiao Hospital
name: Nanfang Hospital, Southern Medical University
name: First Affiliated Hospital Xi'an Jiaotong University
name: Ruijin Hospital
name: Affiliated Hospital of Guangdong Medical University
name: The Third Xiangya Hospital of Central South University
First posted: 2016-11-17
Enrollment: 1114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Transanal or Laparoscopic Total Mesorectal Excision treat rectal cancer
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease-free survival
timeFrame: 3 years
measure: Overall survival
timeFrame: 5 years
Secondary outcomes:
measure: Positive circumferential resection margin (CRM)
timeFrame: 3 years
measure: Overall survival
timeFrame: 10 years
measure: Mesorectal completeness
timeFrame: 3 years
measure: Number of retrieved lymph nodes
timeFrame: 3 years
measure: Morbidity rate
timeFrame: 1 years
measure: Mortality rate
timeFrame: 1 years
measure: Anorectal function outcomes
timeFrame: 3 years
measure: Sexual functional outcomes
timeFrame: 3 years
measure: The patient's Quality of life: EORTC QLQ-30 questionnaire
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
state: Beijing
city: Chongqing
country: China
facility: Department of General Surgery, Daping Hospital, Army Medical university
state: Chongqing
city: Guangzhou
country: China
facility: Department of colorectal surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Zhanjiang
country: China
facility: The Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital of University of South China
state: Hunan
city: Changchun
country: China
facility: Department of Gastrointestinal Surgery, The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Department of Colorectal Surgery, Shengjing Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University,
state: Shanghai
city: Nanchong
country: China
facility: Department of Gastrointestinal Surgery，The Affiliated Nanchong Central Hospital of North Sichuan Medical College
state: Sichuan
city: Yibin
country: China
facility: Department of gastrointestinal surgery, the Second People's Hospital of Yibin
state: Sichuan
city: Chongqing
country: China
facility: XinQiao Hospital of Army Medical University
Study officials:
affiliation: The Sixth Affiliated Hospital, Sun Yat-sen University
name: Jianping Wang, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.