Transanal vs Laparoscopic Total Mesorectal Excision and 3-Year Disease-Free Survival in Rectal Cancer: The TaLaR Randomized Clinical Trial

Abstract

Importance: Previous studies have demonstrated the advantages of short-term histopathological outcomes and complications associated with transanal total mesorectal excision (TME) compared with laparoscopic TME. However, the long-term oncological outcomes of transanal TME remain ambiguous. This study aims to compare 3-year disease-free survival of transanal TME with laparoscopic TME.

Objective: To evaluate 3-year disease-free survival between transanal TME and laparoscopic TME in patients with rectal cancer.

Design, setting, and participants: This randomized, open-label, noninferiority, phase 3 clinical trial was performed in 16 different centers in China. Between April 2016 and June 2021, a total of 1115 patients with clinical stage I to III mid-low rectal cancer were enrolled. The last date of participant follow-up was in June 2024.

Interventions: Participants were randomly assigned in a 1:1 ratio before their surgical procedure to undergo either transanal TME (n = 558) or laparoscopic TME (n = 557).

Main outcomes and measures: The primary end point was 3-year disease-free survival, with a noninferiority margin of -10% for the comparison between transanal TME and laparoscopic TME. Secondary outcomes included 3-year overall survival and 3-year local recurrence.

Results: In the primary analysis set, the median patient age was 60 years. A total of 692 male and 397 female patients were included in the analysis. Three-year disease-free survival was 82.1% (97.5% CI, 78.4%-85.8%) for the transanal TME group and 79.4% (97.5% CI, 75.6%-83.4%) for the laparoscopic TME group, with a difference of 2.7% (97.5% CI, -3.0% to 8.1%). The lower tail of a 2-tailed 97.5% CI for the group difference in 3-year disease-free survival was above the noninferiority margin of -10 percentage points. Furthermore, the 3-year local recurrence was 3.6% (95% CI, 2.0%-5.1%) for transanal TME and 4.4% (95% CI, 2.6%-6.1%) for laparoscopic TME. Three-year overall survival was 92.6% (95% CI, 90.4%-94.8%) for transanal TME and 90.7% (95% CI, 88.3%-93.2%) for laparoscopic TME.

Conclusions and relevance: In patients with mid-low rectal cancer, 3-year disease-free survival for transanal TME was noninferior to that of laparoscopic TME.

Trial registration: ClinicalTrials.gov Identifier: NCT02966483.

Figure 1.. Flow of Patient Enrollment and Randomization

TME indicates total mesorectal excision. ^aSurgeons decided to perform the abdominoperineal resection (Miles operation) procedure, according to the specific intraoperative circumstances. The Miles operation is used for the treatment of rectal cancers, involving the removal of the distal colon, rectum, and anal sphincter complex, resulting in a permanent colostomy. ^bTwo patients randomized to undergo transanal TME did not provide proper consent; hence, their data could not be used in any analysis. ^cPatients were found to have peritoneal metastasis (n = 1) or liver metastasis (n = 1) intraoperatively. ^dAfter the procedure, the patient refused to participate and have their data used in any analysis. ^eThe primary analysis set excluded patients who were later discovered not to have met the inclusion criteria at baseline.

Figure 2.. Cumulative Probability of Recurrence or Death for Transanal Total Mesorectal Excision (TME) vs Laparoscopic TME Within 3 Years of Procedure^a

^aRecurrences and deaths indicate new incidents at each time point.

Figure 3.. Difference in 3-Year Disease-Free Survival Between Transanal Total Mesorectal Excision (TME) and Laparoscopic TME Groups^a

^aDifference between transanal TME and laparoscopic TME was 2.7% (97.5% CI, −3.0% to 8.1%). ^bTransanal TME − laparoscopic TME.