COLOR III Trial: Transanal vs Laparoscopic TME

Background Surgery for mid and low rectal cancer is associated with relative high rates of incomplete mesorectal excisions and high rates of circumferential resection margin (CRM) involvement resulting in significant number of local recurrences. Moreover, patients with mid and low rectal cancer suffer from high rates of morbidity, permanent colostomies and impairment of quality of life. The transanal TME (TaTME) has been developed to improve the quality of TME surgery in mid and low rectal cancer. Study design The COLOR III trial is an international multicentre randomised study comparing short- and long-term outcomes of TaTME and laparoscopic TME for rectal cancer. The study will include a quality assessment phase before randomisation to ensure required competency level and uniformity of the new TaTME technique and the laparoscopic TME. During the trial clinical data will be reviewed centrally to ensure uniform quality. Endpoints The primary endpoint of the study is the local recurrence rate at 3-years follow-up. Secondary endpoints include sphincter saving procedures, short-term morbidity and mortality, involved circumferential resection margin (CRM), disease-free and overall survival at 3 and 5 years, completeness of mesorectum and quality of life. Statistics In laparoscopic TME the percentage of local recurrence at 3-years follow-up is estimated 5%. With the non-inferiority margin set at 4%, with a one-sided level of significance of 2.5% and a power of 80%, a total of 1104 patients is needed, 669 patients in the TaTME arm and 335 patients in the laparoscopic TME arm. All analyses will be performed on intention-to-treat basis. Main selection criteria Patients with histologically proven single mid or distal rectum carcinoma (0 to 10 cm from anal verge) at MRI, eligible for restorative surgery with a curative intent, are included. Patients with a T1 tumor suitable for local excision, T3 tumors with a suspected involved circumferential resection margin and T4 tumors are excluded. Hypothesis The hypothesis is that TaTME will result in a comparable local recurrence rate at 3-years follow-up with benefit of lower morbidity and conversions. Furthermore, because of direct endoscopic visualization, even in very low tumors a coloanal anastomosis can be created, resulting in a lower colostomy rate compared with laparoscopic and open resection. Because long-term outcomes are unknown, within a trial setting the technique can be standardized and quality control can be performed.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Solitary mid (5.1-10cm from anal verge on MRI) or low (0-5cm from anal verge on MRI) rectal cancer observed at colonoscopy and histologically proven through biopsy
* Distal border of the tumour within 10cm from the anal verge on MRI-scan
* Tumour with threatened margins downstaged after neoadjuvant therapy to free margins
* No evidence for distal metastases on imaging of thorax and abdomen
* Suitable for elective surgical resection
* Informed consent according to local requirements

Exclusion Criteria:

* T3 tumours with margins less than 1mm to the MRF, determined by MRI-scan (as staged after preoperative chemo- and/or radiotherapy)
* T4 tumours, as staged after preoperative chemo- and/or radiotherapy
* Tumours with in growth more than 1/3 of anal sphincter complex or levator ani
* Malignancy other than adenocarcinoma at histological examination
* Patients under 18 years of age
* Pregnancy
* Previous rectal surgery (excluding local excision, EMR (endoscopic mucosal resection) or polypectomy)
* Signs of acute intestinal obstruction
* Multiple colorectal tumours
* Familial Adenomatosis Polyposis Coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative colitis
* Planned synchronous abdominal organ resections
* Preoperative suspicion of invasion of adjacent organs through MRI-scan
* Preoperative evidence for distant metastases through imaging of the thorax and abdomen
* Other malignancies in medical history, except adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri
* Absolute contraindications to general anaesthesia or prolonged pneumoperitoneum, as severe cardiovascular or respiratory disease (ASA class \> III)

• DERIVEDTuynman JB, Yao H, Moolenaar LR, Sietses C, Hompes R, Aigner F, Caycedo-Marulanda A, Chen CC, Deeb M, Doornebosch PG, Feng B, Foo CC, Furst A, Ito M, de Lacy FB, Leao P, Maykel JA, Muratore A, van Oostendorp SE, Park SC, Pedziwiatr M, Ren M, Seitinger G, Stockmann HBAC, Talsma AK, Turler A, Tong W, Wang Q, Xu Q, Zhang H, van Waesberghe JTM, Ali M, Twisk JWR, Zhang Z, de Lacy AM, Hanna GB, Bonjer HJ; COLOR III Study Group. Transanal total mesorectal excision versus laparoscopic total mesorectal excision for mid and low rectal cancer (COLOR III): short-term outcomes of an international, multicentre, phase 3, randomised, controlled, non-inferiority trial. Lancet Gastroenterol Hepatol. 2026 May;11(5):355-366. doi: 10.1016/S2468-1253(26)00022-1. Epub 2026 Mar 23. PMID 41887239