Neoadjuvant Therapy Lengthens Surgery Time but Not Complication Risk in Transanal Rectal Cancer Operations

Rectal cancer surgery is among the most technically demanding operations in abdominal oncology, and one of its newest refinements—transanal total mesorectal excision, or TaTME—has sparked both enthusiasm and debate since its introduction. Now, one of the largest multicenter analyses to date has examined how preoperative neoadjuvant therapy, the chemotherapy and radiotherapy given before surgery to shrink tumors and improve outcomes, affects the safety and feasibility of this approach. The findings, drawn from 26 Japanese surgical centers, offer reassurance on complication rates while highlighting a measurable cost in the operating room: longer surgery.

The study, published in Annals of Gastroenterological Surgery, drew on the nationwide Ta-Ta-Mi registry, which captured 706 patients who underwent TaTME at 26 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. From this pool, 679 patients with primary rectal cancer were eligible for the current analysis, all operated on between January 2012 and December 2019. The researchers focused on tumors whose distal edge lay within 12 centimeters of the anal verge—the mid and low rectum, where surgical access is most difficult and where total mesorectal excision, the meticulous removal of the fatty envelope surrounding the rectum, is critical for local tumor control.

TaTME was developed specifically to overcome the limitations of conventional laparoscopic pelvic dissection, which becomes notoriously awkward in male patients, obese patients, and those with narrow pelvises or low-lying tumors. By entering through the anus and working upward, surgeons gain improved visualization and instrument maneuverability in the deepest part of the pelvis. A network meta-analysis of 29 randomized controlled trials involving 6,237 patients previously found broadly comparable perioperative and oncological outcomes across open, laparoscopic, robotic, and transanal approaches, though laparoscopic surgery carried a higher risk of circumferential resection-margin involvement than the transanal route. What remained unclear, however, was how neoadjuvant therapy—now increasingly given as total neoadjuvant therapy, or TNT, to boost pathological complete response rates—changes the picture for TaTME specifically.

To answer that question, the research team employed propensity score matching, a statistical technique designed to mimic randomization in observational data. Patients who received neoadjuvant therapy were matched one-to-one with those who went straight to surgery, balancing the groups on age, sex, body mass index, American Society of Anesthesiologists physical status, the tumor markers CEA and CA19-9, previous abdominal surgery, and clinical tumor stage. After matching, 294 patients—147 in each arm—formed the comparison cohort, with standardized mean differences confirming good balance across nearly all prespecified covariates. The primary endpoint was severe postoperative complications, defined as Clavien–Dindo grade III or higher, a scale that grades complications from mild deviations to life-threatening events requiring invasive intervention.

The headline result was striking in its clarity on one front and its ambiguity on another. Severe complications occurred in 12.2 percent of the non-neoadjuvant group and 10.9 percent of the neoadjuvant group—an adjusted odds ratio of 0.90 with a confidence interval spanning 0.44 to 1.85, far from statistical significance. Sensitivity analyses using conventional multivariable logistic regression, Firth logistic regression, and marginal standardization on the full cohort of 676 patients likewise found no significant association. Yet the researchers were careful to note that the confidence intervals remained wide, meaning clinically relevant benefit or harm could not be excluded. The overall severe complication rate of 11.6 percent in the matched cohort sits comfortably within the 10 to 15 percent range reported in previous multicenter trials, lending external consistency to the findings.

Operative time told a different story. Patients who had received neoadjuvant therapy spent a median of 510 minutes in the operating room, compared with 382 minutes for those who had not—an adjusted mean difference of nearly 130 minutes, highly statistically significant. This association persisted even after accounting for body mass index, operative procedure, lateral pelvic lymph node dissection, and abdominal approach, with neoadjuvant therapy independently associated with a 14 percent increase in operative time. Even among patients who did not undergo lateral lymph node dissection, a procedure that itself dramatically lengthens surgery, neoadjuvant therapy remained linked to a 13.9 percent longer operation. The researchers attribute the delay to treatment-associated tissue edema, fibrosis, and less distinct anatomical planes—changes that make the deep pelvic dissection inherently more laborious, though residual confounding cannot be ruled out.

The multivariable analysis of the full cohort painted a richer portrait of what drives operative duration. Male sex, higher body mass index, previous abdominal surgery, more advanced clinical T stage, lateral lymph node dissection, abdominoperineal resection, and an open surgical approach all independently lengthened the operation, while a two-team transanal approach—simultaneous abdominal and perineal dissection—shortened it by nearly 18 percent. Notably, bilateral lateral lymph node dissection added more than 50 percent to operative time, underscoring just how much the extent of nodal surgery shapes the surgical workload, yet the absence of a significant interaction between neoadjuvant therapy and lymph node dissection extent suggests the two effects operate independently.

Pathological findings revealed the biological footprint of preoperative treatment. Lymphatic invasion was significantly less frequent in the neoadjuvant group—23.8 percent versus 43.5 percent—and venous invasion showed an even starker reduction, 38.8 percent versus 64.6 percent, both with p values below 0.001. These changes reflect the known treatment-related pathological response to neoadjuvant therapy, in which chemotherapy and radiation systematically eradicate tumor cells that have invaded lymphatic and blood vessels. Tumor budding grades also differed, with no BD3 cases in the neoadjuvant group compared with 10 in the non-neoadjuvant arm. No significant differences emerged in p/ypT category, p/ypN status, perineural invasion, or tumor differentiation.

Perhaps most clinically reassuring were the resection-margin results. Distal margin positivity was vanishingly rare in both groups—0.7 percent each—and circumferential resection-margin involvement, defined as a tumor-to-margin distance of 1 millimeter or less, occurred in 7.8 percent of evaluable non-neoadjuvant patients and 5.7 percent of neoadjuvant patients, a non-significant difference. This matters because fibrosis and tissue edema after neoadjuvant therapy could theoretically obscure the dissection plane and increase the risk of an inadequate margin. In this multicenter cohort treated at experienced centers, TaTME after neoadjuvant therapy showed no such penalty.

An unexpected observation was that anastomotic leakage—the leakage of bowel contents from a surgical connection—occurred in only 3.4 percent of neoadjuvant patients undergoing low anterior or intersphincteric resection, compared with 11.7 percent of non-neoadjuvant patients. The authors caution that this finding is exploratory: tumor regression after neoadjuvant therapy may facilitate distal rectal transection and reconstruction, but differences in patient selection, anastomotic technique, and perfusion assessment that were not captured in the database could also explain the gap, and the absolute number of leakage events was small. The regimen-specific analysis, comparing neoadjuvant chemotherapy, chemoradiotherapy, total neoadjuvant therapy, and radiotherapy alone, found no statistically significant differences in severe complications or operative time after adjustment, though the descriptive data suggested radiotherapy alone produced the longest operations.

The study carries important limitations that temper its conclusions. As a retrospective observational analysis, treatment assignment was not randomized, and the neoadjuvant group included only patients who ultimately proceeded to TaTME—those who developed disease progression or severe toxicity before surgery were not captured, meaning the findings apply to selected surgical candidates rather than the complete treatment strategy. Neoadjuvant regimen selection, lymph node dissection criteria, and sphincter-preserving indications were not standardized across institutions, the interval between treatment completion and surgery was unavailable, and pathological assessment was performed locally without centralized review. All participating centers were experienced Japanese institutions, which may limit generalizability to other healthcare systems.

Nevertheless, the nationwide multicenter design and the depth of clinical, operative, and pathological data represent substantial strengths, and the consistency of the severe-complication findings across multiple statistical approaches strengthens confidence in the central message. For surgeons and patients weighing the timing of therapy before transanal rectal cancer surgery, the evidence suggests that preoperative neoadjuvant treatment, while adding meaningful time under anesthesia, does not appear to compromise the safety profile or the quality of the oncological resection in experienced hands. As total neoadjuvant therapy continues to expand globally in the pursuit of higher pathological complete response rates and improved systemic disease control, these findings provide a practical foundation for surgical planning in the era of increasingly intensive preoperative treatment.

Subject of Research: Short-term surgical outcomes of transanal total mesorectal excision for rectal cancer with and without preoperative neoadjuvant therapy

Article Title: Short‐Term Outcomes of Transanal Total Mesorectal Excision for Rectal Cancer: A Multicenter Propensity Score‐Matched Analysis Comparing Patients With and Without Preoperative Neoadjuvant Therapy

Article References: Shima, T., Hamamoto, H., Matsuda, T., Takemasa, I., Tanaka, K., Mukai, T., Watanabe, J., Lee, S.-W., Yamamoto, S., Naitoh, T., & Ta‐Ta‐Mi Study Group Collaborators from the Japan Society of Laparoscopic Colorectal Surgery (2026). Short‐Term Outcomes of Transanal Total Mesorectal Excision for Rectal Cancer: A Multicenter Propensity Score‐Matched Analysis Comparing Patients With and Without Preoperative Neoadjuvant Therapy. Annals of Gastroenterological Surgery, Article ags3.70298. https://doi.org/10.1002/ags3.70298

Image Credits: AI Generated

DOI: 10.1002/ags3.70298

Keywords: rectal cancer, transanal total mesorectal excision, neoadjuvant therapy, total mesorectal excision, propensity score matching, surgical outcomes, anastomotic leakage, Clavien-Dindo complications, chemoradiotherapy, total neoadjuvant therapy, operative time, circumferential resection margin