Evaluate Efficacy, Morbidity and Functional Outcome of Endoscopic TranAnal Proctectomy vs Standard Transabdominal Laparoscopic Proctectomy for Rectal Cancer

Phase 3

• Conditions: Rectal Cancer
• Interventions: Procedure: Standard Transabdominal Laparoscopic Proctectomy; Procedure: ETAP

• Registration Number: NCT02584985
• Lead Sponsor: Institut Paoli-Calmettes

Brief Summary

Standard surgical treatment of mid and low rectal cancer is total mesorectal excision (TME). Originally performed by open surgery, TME demonstrated improved local control and reduced urogenital morbidity. Laparoscopic approach has been validated by several randomised controlled trials: laparoscopic approach offers to the patient a better post-operative recovery, a lower risk of wound hernia and comparable oncological results. However, the risk of conversion to open procedure remains significant.

Endoscopic Transanal Proctectomy allows retrograd mesorectal excision, performing the whole pelvic dissection via a specific-moderate cost device. The procedure is then completed by a briefer transabdominal laparoscopic step to mobilise the colon and perform inferior mesenteric vessels ligation, prior to low coloanal anastomosis. The originality of this approach is to perform a surgical dissection via an extra peritoneal route, without peritoneal and abdominal wound trauma. This focuses on new technical improvement in the area of mini-invasive pelviabdominal surgery using natural orifice as surgical access. This approach offer closer and better exposure of pelvic dissection plane and could improve oncological quality and pelvic nerve preservation. It could be profitable to postoperative patient outcome. However rates and type of cancer-recurrences as well as functional results have to be assessed in a controlled study. This technique has shown to be feasible and reproducible through early clinical series. Conversion rates appear to be lower than published rates of laparoscopic approach, markedly inferior to 10%. Compiled rates of morbidity (27.8%), R1 resection\* (6%), mesorectum macroscopic integrity (100%) appear to be comparable to laparoscopic approach results. However functional results as well as urologic morbidity have to be evaluated in comparative studies. In a preliminary retrospective comparative (n=72) we founded comparable oncological quality criteria (R1 resection 5.9% vs 10.5% p 0.74, Grade 3 mesorectal integrity 57.5 vs 56.2 p 0.99), lower conversion rate to open procedure (2.9% vs 23.6% p 0.011), shorter in-hospital stay (8 vs 9 days p 0.038). Comparable morbidity rates (Dindo 1-4 27% vs 34% p 0.52) and functional results (Kirwan 1/2 80.3% vs 80.6% p 0.94) were also founded. These data need to be confirmed. To this date, Endoscopic Transanal Proctectomy has been evaluated through preliminary studies including several short series demonstrating the feasibility of the technique and showing low morbidity. For some authors the benefit of transanal approach is significant in difficult cases such as male patient and narrow pelvis. Very recently, two non randomised comparative studies were published with conclusions close to those in our study.

Investigators propose, with the support of the GRECCAR group, to conduct a national, multicenter, open-label randomized study based on oncological non-inferiority (R1 resection rate) for the main objective, comparing Endoscopic Transanal Proctectomy to Standard Transabdominal Laparoscopic Proctectomy, for low lying rectal cancer requiring manual colo-anal anastomosis. There is a clear expected benefit expected for the patients through the ETAP procedure in term of post operative short term outcome, risk of conversion to open procedure, risk of wound hernia.This trial could also show significant advantages in terms of quality of dissection, quality of the specimen, quality of nerve preservation.

Detailed Description

The main objective of study is to assess if R1 resection rate of Endoscopic Transanal Proctectomy (ETAP) is not meaningfully inferior to Standard Laparoscopic TME for low lying rectal cancer requiring manual colo-anal anastomosis. The secondary objective will evaluate conversion rate, mini invasive level of abdominal approach postoperative morbidity, In hospital length of stay, Mesorectum macroscopic assessment, Functional urologic and sexual results, Fecal Continency, global QoL, stoma-free survival, disease-free survival at 3 years. Patients with non metastatic rectal adenocarcinoma requiring coloanal anastomosis will be considered for the study. Based on the non-inferiority hypothesis, the population estimated in this study at 226 patients, 113 for each arm. Inclusion period will be 3 years, the study will be running for 6 years.

Study Timeline

• Study First Submitted: 2015-10-15
• Study First Submitted QC: 2015-10-22
• Study First Posted: 2015-10-23
• Study Start: 2016-01
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-22
• Last Update Posted: 2019-01-23
• Primary Completion: 2021-01
• Study Completion: 2024-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 226

Inclusion Criteria

• Non metastatic stadified T3 rectal adenocarcinoma allowing sphincter-sparing procedure
• Tumor location or local condition justifying manual coloanal anastomosis
• Age >18 years
• Patient eligible for surgery
• Written informed consent
• Affiliation to Social Security System

Exclusion Criteria

• Tumor stadified T4 with en-bloc resection
• Possible mechanical trans-sutural anastomosis
• Distant metastasis at diagnosis
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule
• Patients deprived of liberty or placed under the authority of a tutor

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Transabdominal Laparoscopic proctectomy	Standard Transabdominal Laparoscopic Proctectomy	Primary transanal conventional dissection (sphincter preservation assessment) or not, type of laparoscopic approach multiport or singleport, level of arterial section, extension of colonic mobilization, conditions of mesorectal excision and nerve preservation, site for specimen extraction (transanal / transabdominal) and type of colonic reconstruction.
ETAP : Endoscopic Transanal Proctectomy	ETAP	1. Primary transanal approach : Careful positioning in Lithtomy, dilatation and anal exposure with standard retractor. Mucosa incision and internal sphincter dissection according to tumor extension. Primary conventional dissection up to circumferential exposure of fascia recti. Secondary implantation of transanal endoscopic device Begin mesorectal endoscopic dissection postero-anteriorly, then laterally with nerve-sparing dissection. Level assessment of posterior dissection (vertical segment). End with peritoneal opening anteriorly (Douglas). 2. Secondary transabdominal approach : Type of laparoscopic approach multiport or singleport. Level of arterial section, extension of colonic mobilization, site for specimen extraction (transanal / transabdominal), type of colonic reconstruction.

Primary Outcome Measures

Name	Time	Method
R1 resection rate	from surgery up to 3 years	R1 resection rate defined as circumferential resection margin (CRM) ≤ 1 mm, distal or positive margin (and the complete rectal resection meso levels (grade III) as classified by Quirke).

Secondary Outcome Measures

Name	Time	Method
Failure rate (conversion to open)	During surgery
Disease-free survival at 3 years	3 years from surgery

Trial Locations

Locations (1)

Institut Paoli-Calmettes; 🇫🇷 Marseille, France