Transanal Versus Laparoscopic Total Mesorectal Excision for Mid and Low Rectal Cancer (TaLaR): a Multicentre Randomised Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,114
- 试验地点
- 16
- 主要终点
- Disease-free survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Disease-free survival
时间窗: 3 years
Disease-free survival
Overall survival
时间窗: 5 years
Overall survival
次要结局
- Overall survival(10 years)
- Number of retrieved lymph nodes(3 years)
- Morbidity rate(1 years)
- Mortality rate(1 years)
- Positive circumferential resection margin (CRM)(3 years)
- Mesorectal completeness(3 years)
- Anorectal function outcomes(3 years)
- Sexual functional outcomes(3 years)
- The patient's Quality of life: EORTC QLQ-30 questionnaire(3 years)
研究者
Yanhong Deng
MD
Sun Yat-sen University