Transanal Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer

Официальное название

Transanal Versus Laparoscopic Total Mesorectal Excision for Mid and Low Rectal Cancer (TaLaR): a Multicentre Randomised Clinical Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура TaTME
  Transanal Total Mesorectal Excision
• Процедура LpTME
  Conventional Laparoscopic Total Mesorectal Excision

Первичные конечные точки

• Disease-free survival [Срок оценки: 3 years]
• Overall survival [Срок оценки: 5 years]

Вторичные конечные точки (9)

• Positive circumferential resection margin (CRM) [Срок оценки: 3 years]
• Overall survival [Срок оценки: 10 years]
• Mesorectal completeness [Срок оценки: 3 years]
• Number of retrieved lymph nodes [Срок оценки: 3 years]
• Morbidity rate [Срок оценки: 1 years]
• Mortality rate [Срок оценки: 1 years]
• Anorectal function outcomes [Срок оценки: 3 years]
• Sexual functional outcomes [Срок оценки: 3 years]
• The patient's Quality of life: EORTC QLQ-30 questionnaire [Срок оценки: 3 years]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 16 центров

• Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical — Пекин
• Department of General Surgery, Daping Hospital, Army Medical university — Чунцин
• Department of colorectal surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University — Гуанчжоу
• Nanfang Hospital — Гуанчжоу
• The Affiliated Hospital of Guangdong Medical University — Zhanjiang
• Affiliated Hospital of Zunyi Medical University — Zunyi
• The Third Xiangya Hospital of Central South University — Чанша
• The First Affiliated Hospital of University of South China — Hengyang
• … и ещё 8 центров

Публикации

• 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. PMID 26220109
• 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. PMID 26310534
• Zeng Z, Luo S, Zhang H, Wu M, Ma D, Wang Q, Xie M, Xu Q, Ouyang J, Xiao Y, Song Y, Feng B, Xu Q, Wang Y, Zhang Y, Shi L, Ling L, Zhang X, Huang L, Yang Z, Peng J, Wu X, Ren D, Huang M, Lan P, Wang J, Tong W, Ren M, Liu H, Kang L; Chinese Transanal Endoscopic Surgery Collaborative (CTESC) Group. Transanal vs Laparoscopic Total Mesorectal Excision and 3-Year Disease-Free Survival in Rectal Cancer: T PMID 39847361
• Chen M, Ye F, Huang P, Liang Z, Liu H, Zheng X, Li W, Luo S, Kang L, Huang L. Inflammatory stress response after transanal vs laparoscopic total mesorectal excision: a cohort study based on the TaLaR trial. Int J Surg. 2024 Jan 1;110(1):151-158. doi: 10.1097/JS9.0000000000000838. PMID 37916926
• 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. PMID 31586244

Идентификаторы

NCT: NCT02966483 · SYSU-RECTAl-2016

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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