Surgical management of mid and low rectal cancer remains technically challenging, particularly in a narrow pelvis and for low tumors. Transanal Total Mesorectal Excision (TaTME) facilitates distal pelvic dissection and enables low anastomoses for mid and low rectal cancer, although its oncological safety remains unclear.
The COLOR III trial was designed to compare TaTME with laparoscopic TME (LapTME) in an international randomized setting.
This study was published in The Lancet Gastroenterology & Hepatology on March 23, 2026.
Title: 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
Authors: Jurriaan B. Tuynman, Hongwei Yao, Laura R. Moolenaar, Colin Sietses, Roel Hompes, Felix Aigner, Antonio Caycedo–Marulanda, Chien-Chih Chen, Muneer Deeb, Pascal G. Doornebosch, Bo Feng, Chi-Chung Foo, Alois Fürst, Masaaki Ito, Francisco B. de Lacy, Pedro Leão, Justin A. Maykel, Andrea Muratore, Stefan E. van Oostendorp, Sung Chan Park, Michał Pędziwiatr, MingYang Ren, Gerald Seitinger, Hein B.A.C. Stockmann, Aaldert K. Talsma, Andreas Türler, Weidong Tong, Quan Wang, Qing Xu, Hongyu Zhang, Jan-Hein T.M. van Waesberghe, Mahsoem Ali, Jos W.R. Twisk, Zhongtao Zhang, Antonio M. de Lacy, George B. Hanna, Hendrik J. Bonjer.
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Methods
COLOR III is an open-label, international phase 3 trial conducted across 28 hospitals, enrolling patients with (y)cT1–3N0–2M0 rectal adenocarcinoma located within 10 cm of the anal verge. Participants were randomized in a 2:1 ratio to TaTME or laparoscopic TME. Randomisation was performed 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.
While the primary endpoint—3-year local recurrence—is still under evaluation, this report focuses on short-term outcomes, including perioperative safety, conversion rates, anastomotic leakage, and pathological quality of resection. The trial is registered at ClinicalTrials.gov (NCT02736942).
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Results
A total of 1103 patients were randomized, with 711 in the TaTME group and 350 in the laparoscopic group included in the modified intention-to-treat analysis. Baseline characteristics were well balanced, with a median age of 63 years and a predominance of male patients.
TaTME was associated with a marked reduction in conversion to open surgery, occurring in 1% of patients compared with 17% in the laparoscopic group (OR 0.03, 95% CI 0.01–0.08).
Postoperative outcomes were otherwise comparable. The rate of complications within 90 days was similar between groups (20% vs 18%; OR 1.22, 95% CI 0.90–1.64). When stratified by severity, minor complications occurred in 9% versus 8%, and major complications in 11% versus 9% (OR 1.23, 95% CI 0.82–1.85).
Anastomotic leakage rates did not significantly differ, observed in 10% of patients undergoing TaTME and 8% in the laparoscopic group (OR 1.32, 95% CI 0.83–2.08).
Macroscopically complete resection was achieved in 84% of TaTME specimens and 86% of laparoscopic specimens. Resection margin involvement was rare, with positive CRM in four (1%) TaTME procedures versus one (<1%) LapTME procedure, and positive DRM in seven (1%) versus one (<1%), respectively.
TaTME was associated with significantly lower conversion rates, while 90-day morbidity and complete resection rates were similar between groups.
What is a non-inferiority trial?
A non-inferiority trial is a randomized controlled trial designed to determine whether a new intervention is not unacceptably less effective than an established active control treatment already in use. This design has become increasingly important as advances in medical care have reduced the incremental benefits of new therapies, making it more difficult to demonstrate superiority, and because placebo-controlled trials may be unethical when effective treatments are available.
A key methodological feature is the non-inferiority margin (Δ), which defines the maximum acceptable loss of efficacy that would still be considered clinically acceptable. In this context, non-inferiority trials test the null hypothesis that the experimental treatment is inferior to the active control by at least this margin. Non-inferiority is concluded when the confidence interval for the treatment effect remains within the predefined margin, indicating that any difference in efficacy does not exceed the acceptable threshold.
Importantly, non-inferiority trials are more complex to design, conduct, and interpret than conventional superiority trials. Their validity depends on appropriate selection of the non-inferiority margin, preservation of the effect of the active control, and methodological considerations such as assay sensitivity. Furthermore, failure to demonstrate superiority does not imply non-inferiority, and non-inferiority does not establish equivalence, as these represent distinct statistical concepts (Hahn, 2012).
Difference between TaTME and LapTME
Total mesorectal excision (TME) remains the standard surgical approach in rectal cancer, involving en bloc removal of the rectum together with the surrounding mesorectal envelope, which contains lymphatics, vessels, and regional lymph nodes (Medscape, Maroju et al., 2023). This technique is essential to achieve an intact oncologic specimen and minimize the risk of local recurrence. In contemporary practice, TME can be performed using different minimally invasive approaches.
Laparoscopic TME (LapTME) is carried out through a transabdominal, top-down approach using small incisions, a camera, and specialized instruments, and is widely established in clinical practice.
In contrast, transanal TME (TaTME) is performed through the anal canal in a bottom-up fashion, allowing direct access to the distal rectum and potentially improved visualization in technically challenging cases, such as narrow pelvis, bulky tumors, or very low rectal cancers (Kitaguchi et al., 2023).
Importantly, both techniques share the same oncologic objective—complete mesorectal excision with clear margins—while differing primarily in their surgical access and direction of dissection.
Conclusion
The COLOR III trial shows that 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.
However, long-term oncological outcomes remain to be determined. Patient enrolment has been completed, and follow-up for the primary endpoint is currently ongoing.
The full article available in The Lancet Gastroenterology & Hepatology.