Transanal Total Mesorectal Excision Found Safe, Feasible in U.S. Trial

MONTREAL—Two-team transanal total mesorectal excision (taTME)—a minimally invasive operation that combines abdominal and transanal endoscopic approaches to treat patients with lower rectal cancer—has been shown to be safe and feasible in the first large multicenter trial in North American patients.

The study, which will be published in Surgical Endoscopy, was presented at the 2023 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES).

“This, at least, cements taTME as a viable and safe option for patients if managed by surgeons with the experience,” said Patricia Sylla, MD, a professor of surgery at Mount Sinai Health System, in New York City. Dr. Sylla is the president of SAGES for 2023-2024 and is a member of the editorial board of General Surgery News.

Of the 100 patients in the trial, 90 had a complete or near-complete resection. Two patients had positive margins: one positive circumferential resection margin and the other a positive distal resection margin.

The stoma closure rate was 98% after a median of 154 days. Eighteen patients developed anastomotic complications, including eight after the first 30 days, but 16 of these patients—88.9%—were able to have their ileostomy reversed.

“It was not randomized, but this phase 2 prospective trial should also confirm the safety, the procedural safety and early oncologic results,” Dr. Sylla said in an interview.

As a clinical fellow, Dr. Sylla initiated a transanal, natural orifice, translumenal endoscopic surgery (NOTES) project in a swine model that led to the first clinical use of taTME for rectal cancer in 2009 (Surg Endosc 2010;24[5]:1205-1210). The technique’s uptake by expert rectal cancer surgeons was swift. The approach offered a novel way to resect lower tumors in rectal cancer, which are not easy to access or visualize through laparoscopy. With taTME, surgeons can remove difficult-to-reach tumors through a combination of transanal endoscopy, laparoscopy and robotic surgery, while preserving the sphincters.

But some people were concerned that taTME was picking up steam without long-term data on outcomes. Some evidence suggested that taTME led to high anastomotic leak rates and local recurrences. In 2019, an international registry reported an anastomotic failure rate at 15.7% (Ann Surg 2019;269[4]:700-711). In the same year, surgeons in Norway put a temporary moratorium on the technique after 9.5% of patients in a series of 110 cases developed local recurrences at a median of 11 months of follow-up (Br J Surg 2019;106[9]:1120-1121).

Surgeons in Europe and China set out to answer questions about taTME through randomized controlled trials. To date, only short-term results are available. In January 2023, the Chinese group reported in Annals of Surgery that after randomizing 1,115 patients, there were no significant differences in surgical safety or pathologic outcomes between taTME and laparoscopic TME (Ann Surg 20231;277[1]:1-6).

In that same month, Spanish investigators published results from their trial in 116 patients randomized to laparoscopic TME or taTME (Br J Surg 2023;110[2]:150-158). The conversion rate was significantly lower with taTME than laparoscopic TME, at 2% versus 20%. There was no significant difference in anastomotic leakage between surgery types, but it was less common for taTME. With a median follow-up of 39 months, one patient in the taTME group (1.8%) and three in the laparoscopic TME group (6.1%) experienced a local recurrence.

In the United States, surgeons decided to forgo a randomized controlled trial because they did not want to wait up to a decade for results, Dr. Sylla noted. “Most of us felt uncomfortable with the idea of randomizing patients whom we felt would most benefit from taTME, particularly male patients with low rectal tumors, at the highest risk of conversion.”

The investigators chose to do a phase 2 trial instead—a decision that was criticized because the results would not be the highest level of evidence.

They took an unusual approach to funding the trial, creating a first-of-its-kind collaboration among national surgical organizations and industry partners—a model that could set a new standard for funding trials of surgical techniques. The trial was supported by an American Society of Colon and Rectal Surgeons (ASCRS) research foundation grant and supplemented by funds from nine industry partners. These funds were administered/managed by SAGES, which then directed the support to participating institutions.

Between September 2017 and April 2022, 100 patients with stage 1 to 3 tumors underwent taTME. The median distance of the tumors from the anal verge was 5.8 cm.

Of the group, 70 patients were men; they had a median age of 58 years and a median body mass index of 27.8 kg/m². One-third of patients were obese (BMI =30) and two-thirds of tumors were located 6 cm or less from the anal verge. Most of them received neoadjuvant therapy prior to surgery.

Three patients required a major change in operative plan: Two were converted to open and one was converted from transanal to a robotic abdominal approach. Significant intraoperative complications included organ injury in five patients, including one ureteral injury and one suspected carbon dioxide embolism.

The primary end point was the quality of the TME, with 90% graded as complete or near-complete. This result is lower than in the study by Liu et al, which reported successful resection in 98.9% of taTME patients. In the North American study, photographs of TME specimens were reviewed by blinded reviewers. When there was disagreement between the site pathology assessment and the blinded reviewer, reconciliation was undertaken to reach agreement, which led to a major change in final TME grade in 5% of cases.

Univariate regression analysis identified three risk factors for incomplete TME: ASA class greater than 3 (relative risk [RR], 13.50; 95% CI, 1.77-102.47; P=0.0118), increasing time interval between neoadjuvant therapy and taTME (RR, 1.07 per one-week increase; 95% CI, 1.01-1.14; P=0.0297) and intraoperative blood loss (RR, 1.46 per 100 mL; 95% CI, 1.14-1.87; P=0.0027]).

In the first 30 days, postoperative complications occurred in 49 patients. They were mostly ileus, stoma-related dehydration, urinary retention and anastomotic leaks. Eight additional patients had anastomotic complications in the second or third months after surgery. The overall leak rate was 10% at 30 days and 18% after 90 days.

All late anastomotic complications were resolved and the ileostomy reversed.

Session moderator H. Jaap Bonjer, MD, PhD, a professor of surgery at the Amsterdam University Medical Center, said the study was “a great collective effort with this difficult procedure.”

Surgeons who perform taTME must be expert rectal cancer surgeons, Dr. Sylla noted. Surgeons who participated in the trial were beyond their learning curves, and had been performing taTME for at least three years and had done at least five cases in the 12 months leading up to the trial. Their skills were assessed by review of unedited taTME videos to ensure they adhered to the principles of taTME.

Careful patient selection is also key, she added. This technique is indicated for patients with resectable tumors in the low rectum, threatening the sphincters, where the risk for conversion and of permanent stoma is high with laparoscopic or robotic TME.

“This is exactly what the taTME approach is useful for, and to be able to demonstrate that it’s safe, even in these hostile pelvises, is very powerful,” Dr. Sylla said. “So hopefully, this will put a little bit of rest to the controversy.”