TAMIS vs ESD for the removal of rectal polyps.

Rationale: Colorectal cancer (CRC) is the second most prevalent cancer in the Netherlands, with 15,000 new cases per year and 5000 colorectal cancer related deaths. The Dutch National Colorectal Cancer screening program began in 2014 and is expected to save 1400 lives per year in the short term through early diagnosis and treatment of cancer. In the longer term it is expected to save an additional 1000 lives per year through the prevention of cancer by removing advanced polyps. In the last few years two new highly promising innovative approaches have become available for minimally invasive en bloc resection of large non-pedunculated rectal lesions. One is a new surgical technique called transanal minimally invasive surgery (TAMIS) and the other is a new endoscopic technique called endoscopic submucosal dissection (ESD). Although both techniques are standard of care in the Netherlands, a direct randomised comparison between TAMIS and ESD is lacking. Therefore, the choice for either of both therapies remains operator-dependent instead of evidence-based.

Objective: The aim of this study is to compare both procedures with regard to recurrence rates and complete (R0) resection rate, and to put this into perspective against the costs and complication rates of both strategies and the burden perceived by patients in both the short and long term.
Hypothesis: We hypothesize that ESD will be associated with longer procedure times but lower costs. For lesions that prove to be benign, we hypothesize that ESD will lead to a higher number of R0 resections and lower recurrence rates, particularly for lesions involving the dentate line, and less serious complications than TAMIS. For lesions that prove to be invasive we hypothesize that TAMIS will have a higher R0 resection rate but that this will not translate to a reduced need for additional surgery.
Study design: Multicentre randomised controlled trial
Study population: Patients 18 years of age or older with a non-pedunculated polyp in the rectum with endoscopic features suspicious for early invasion, found during screening, surveillance or diagnostic colonoscopy.
Intervention: In the TAMIS-arm, resection will be performed using the TAMIS technique, whereas patients randomised to the ESD-arm will undergo resection using the ESD technique.

Endpoints: The primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints: 1. Radical (R0-) resection rate 2. Perceived burden and quality of life, 3. Cost effectiveness at 24 months, 4. Surgical referral rate at 24 months, 5. Complication rate, 6. Recurrence rate at 24 months.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The two resection techniques investigated in this study are standard care in the Netherlands and thus will not contain any additional risks for participating patients. Certain procedures that are optional but recommended in standard care will be performed in all participating patients, including (1) Endoscopic ultrasound of the lesion, (2) MRI of the rectum and (3) biopsies of the scar at follow-up rectoscopies. Follow-up rectoscopy is standard care after resection of an adenoma, and will be performed 6 and 24 months after resection as recommended by the current Dutch guideline for colonoscopy surveillance. The questionnaires to evaluate patients’ burden and quality of life are grouped as much possible to limit the frequency of questionnaires. Taken together, neither an unacceptable risk nor a direct benefit is expected for patients participating in this study. This study will increase current knowledge as to the preferred minimally invasive resection method, which is currently unknown. This is important as the detection rate of these adenomas is expected to further increase with the introduction of the Dutch CRC screening program. The study will therefore support an optimal use of healthcare resources in the future.

We hypothesize that ESD will be associated with longer procedure times but lower costs. For lesions that prove to be benign, we hypothesize that ESD will lead to a higher number of R0 resections and lower recurrence rates, particularly for lesions involving the dentate line, and less serious complications than TAMIS. For lesions that prove to be invasive we hypothesize that TAMIS will have a higher R0 resection rate but that this will not translate to a reduced need for additional surgery.

The primary outcome (recurrent polyp) is measured after 6 months and 12 months by endoscopy.

QOL will be measured by questionnairesat baseline, 4 days, 4 weeks, 6 months and 12 months.

In the TAMIS-arm, resection will be performed using the TAMIS technique, whereas patients randomised to the ESD-arm will undergo resection using the ESD technique.