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

Abstract

Background: Transanal total mesorectal excision (TaTME) facilitates distal pelvic dissection and enables low anastomoses for mid and low rectal cancer, potentially avoiding permanent colostomy. However, its oncological safety remains unclear. The COLOR III trial aimed to compare oncological outcomes between TaTME and laparoscopic TME (LapTME). Here, we report the short-term secondary outcomes.

Methods: This international, multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial was conducted at 28 hospitals globally. Patients (aged ≥18 years) with (y)cT1-3N0-2M0 rectal adenocarcinoma located 10 cm or less from the anal verge were randomly assigned (2:1) to TaTME or LapTME through an interactive web-response system. Randomisation was done using minimisation with stratification for sex, BMI, tumour stage, tumour height, preoperative radiotherapy, and downstaging after chemoradiotherapy. Quality assurance included pre-trial video-based competency assessment and central MRI evaluation for patient eligibility. The primary endpoint, assessed for non-inferiority, is 3-year local recurrence. Short-term secondary endpoints included conversion, 90-day morbidity, anastomotic leakage, specimen quality, and circumferential resection margin (CRM) and distal resection margin (DRM) involvement. All analyses were conducted according to the modified intention-to-treat principle (analysed based on initial allocation but excluded from the analysis after randomisation if they did not undergo surgery or if they were ineligible for surgery after randomisation). The trial is registered at ClinicalTrials.gov (NCT02736942). Patient recruitment has been completed and long-term follow-up for the primary endpoint is ongoing.

Findings: Between Jan 2, 2017 and Jan 16, 2024, 1205 patients were screened for eligibility, of whom 1103 were randomly assigned (735 to TaTME and 367 to LapTME). The modified intention-to-treat population consisted of 711 patients in the TaTME group and 350 in the LapTME group. Patients were predominantly male (717 [68%] male patients vs 344 [32%] female patients), with a median age of 63·0 years (IQR 55·0-70·0) and a median BMI of 24·4 kg/m² (22·2-26·9). Conversion was significantly less frequent with TaTME than with LapTME (four [1%] of 696 patients vs 56 [17%] of 339; adjusted odds ratio [OR] 0·03 [95% CI 0·01-0·08]). Postoperative complications within 90 days were similar between groups (138 [20%] of 689 with TaTME vs 59 [18%] of 335 with LapTME; adjusted OR 1·22 [95% CI 0·90-1·64]). Minor morbidity (Clavien-Dindo grade ≤2) occurred in 61 (9%) of 689 participants in the TaTME group versus 26 (8%) of 333 in the LapTME group, and major morbidity (Clavien-Dindo grade ≥3) in 77 (11%) of 689 versus 31 (9%) of 333 (adjusted OR 1·23 [95% CI 0·82-1·85]). The incidence of anastomotic leakage did not differ between treatment groups (68 [10%] of 689 patients in the TaTME group vs 27 [8%] of 333 patients in the LapTME group; adjusted OR 1·32 [95% CI 0·83-2·08]). Macroscopically complete resection was achieved in 583 (84%) of 692 TaTME specimens vs 291 (86%) of 339 LapTME specimens (adjusted OR 0·94 [95% CI 0·58-1·51]). Resection margin involvement was rare, with positive CRM in four (1%) of 611 TaTME procedures versus one (<1%) of 291 LapTME procedures, and positive DRM in seven (1%) of 690 versus one (<1%) of 334, respectively.

Interpretation: TaTME is a safe surgical technique for mid and low rectal cancer, achieving similar 90-day morbidity and complete resection rates to LapTME, while significantly reducing conversion rates. Long-term follow-up is needed to determine functional and oncological outcomes.

Funding: Dutch Cancer Society, Ethicon EndoSurgery, Medtronic, Applied Medical, and Chinese Institutional funds.