The Role of Transanal Total Mesorectal Excision (TaTME) in the Surgical Management of Rectal Cancer

Introduction

The oncologic principle of total mesorectal excision (TME), introduced by Heald and colleagues,^[1] involves dissection along the mesorectal fascial plane and removing the rectum and mesorectum as one intact specimen. TME is associated with decreased local recurrence and improved cancer-free survival rates and remains the gold standard surgical technique for rectal cancer. Laparoscopic TME has since been demonstrated to have better short-term and long-term surgical outcomes with no significant oncologic differences in local recurrence and disease-free survival in comparison to the open approach.^[2-4]

Despite these advantages, laparoscopic rectal dissection and resection of mid and low rectal tumors can be challenging, particularly in patients with unfavorable anatomic characteristics such as prior pelvic radiation, male sex, a narrow pelvis, and high body mass index (BMI).^[5,6] 

Visualization and dissection with straight laparoscopic instruments in a curved pelvis is technically difficult. In addition, laparoscopic stapling devices may be too large to reliably occlude the distal rectal lumen transversely in a narrow pelvis, requiring multiple crossing staple lines, thereby increasing the risk of anastomotic leak and jeopardizing a clear distal margin.^[7] These technical issues can ultimately lead to high conversion rate to open surgery, lower sphincter preservation rates, and incomplete pathologic specimens with positive distal margins and circumferential radial margins.^[8-12]

Transanal total mesorectal excision (TaTME) emerged as an alternative surgical approach to facilitate caudal to cephalad rectal mobilization and resection of mid and low rectal tumors.^[13] This “bottom-up” approach allows for direct visualization of the distal edge of the tumor providing more accurate distal margin control, particularly for low rectal tumors, thus improving specimen quality and improving rates of organ-sparing procedures compared to conventional “top-down” laparoscopic and robotic approaches.^[14]

Most TaTME procedures are performed in a two-team approach, with abdominal and perineal teams working sequentially or concurrently, resulting in decreased overall operative time.^[15]

Indications

The indications for TaTME include benign and malignant diseases of the mid to low rectum as per recently published international expert consensus guidelines by the TaTME Guidance Group in 2020.^[16]

Guidelines published by the Second International Transanal Total Mesorectal Excision Conference recommend TaTME as a preferred approach for rectal cancer in men, patients with a narrow and/or deep pelvis, visceral obesity and/or obesity with body mass index (BMI) >30 kg/m²,  rectal cancer <12 cm from the anal verge, tumor diameter >4 cm, previous radiotherapy, and prostatic hyperplasia.^[17] 

Patient Preparation

Preoperative consideration of the patient must include staging for cancer and assessment of operative risk. The overall physiologic status of the patient should be evaluated with appropriate preoperative laboratory and imaging studies. Nutritional status should be assessed and addressed when possible.  Stoma marking should be performed.

Procedural Technique

The patient is positioned into lithotomy with the right arm tucked. A foley catheter is placed and attached to the medial thigh with surgical tape to avoid interference with the perineal surgical field. Rigid procto-sigmoidoscopy is performed to confirm the location of the tumor and the rectal lumen is irrigated and sterilized with 10% povidone-iodine solution.

The abdominal and perineal fields are prepped in the standard manner. The abdominal team begins with laparoscopic mobilization of the left colon and proximal rectum, dividing the superior hemorrhoidal pedicle.

The perineal portion begins with effacement of the anus with a LoneStar Retractor System (Cooper Surgical, Inc., Trumbull, CT) to assist in placement of a GelPOINT Path access sleeve (Applied Medical, Inc., Rancho Santa Margarita, CA) into the anal canal with the proximal flange positioned above the anorectal ring. The distal flange is sutured to the perianal skin.

Alternatively, rigid platforms from Karl Storz (Flanders, NJ) or Richard Wolf (Vernon Hills, IL) may be used as per surgeon preference. Intersphincteric dissection may be initially required for very low rectal cancers with involvement of the sphincter complex, after which the transanal access platform can be placed. 

Pneumorectum is achieved using an AirSeal System (ConMed, Inc., Utica, NY). The tumor is visualized and the mucosa is circumferentially scored 1 cm distal to the lowest edge of the tumor to assist in placement of the purse-string suture. A 2-0 Prolene (Ethicon, Inc., Bridgewater, NJ) purse string is used to close the rectal lumen. It is essential to maintain a tight rectal purse string as it prevents spillage of stool or tumor cells into the dissection field and allows insufflation the TME plane.

The rectum is divided full-thickness, circumferentially 1 cm distal to the purse-string using electrocautery, and in doing so, a 2cm distal margin is ensured. The TME plane is entered posteriorly in the presacral plane perpendicular to the rectal lumen to avoid coning in on the mesorectum and creating an incomplete specimen. The TME plane is then entered anteriorly between the rectum and vagina or prostate. The TME dissection is continued laterally until the lateral autonomic nerve fibers are encountered, which mark the lateral dissection plane. It is essential to avoid following the lateral plane anteriorly and mistakenly mobilizing the prostate en bloc with the rectum, potentially injuring the urethra, a particular concern for low lying tumors.^[18]

The TME dissection plane is circumferentially continued proximally until the abdominal dissection plane is met, anteriorly at the cul de sac. The TME dissection is completed circumferentially by incising the remaining peritoneal attachments between the abdominal and perineal fields in a coordinated manner, best accomplished with the two surgical teams working in parallel. 

Specimen extraction may be performed transabdominally or transperineally, depending on specimen bulk and patient anatomy but is most commonly removed via a Pfannenstiel incision. The anastomosis is created by placing the EEA anvil in the proximal colon and suturing a 2-0 Prolene purse string transanally at the open end of the rectal stump. A 19 French Blake drain is passed transanally through the purse string and into the abdominal cavity.

The purse-string is tied down around the drain, which will guide the EEA stapler trocar through the tied purse-string. Care should be taken to ensure that the rectal stump is dissected free of surrounding tissue such as the vagina, prostate, or levators prior purse-string placement. The open EEA stapler trocar is inserted into the end of the drain and is guided through the rectal stump purse-string under direct laparoscopic visualization with assistance from the abdominal team. The abdominal surgeon detaches the drain and mates the proximal colon anvil to the EEA stapler trocar. The perineal surgeon closes and fires the stapler. The staple line is carefully inspected directly through the GelPoint Path device, and an air-leak test is performed. A diverting loop ileostomy may be created to protect the anastomosis, per surgeon preference.  

Short Term Outcomes

Rates of conversion from TaTME to the open approach are relatively low, ranging from 0% to 5.6% according to a TaTME registry.^[19] A propensity score-matched comparison of TaTME with laparoscopic TME found a significantly lower conversion rate in the TaTME group (1.5% vs 8.6%).^[20]

In regard to postoperative morbidity, TaTME demonstrates similar minor and major complication rates when compared to an open or laparoscopic approach, including anastomotic leak, small bowel obstruction, and ileus. Recent systematic reviews found no difference in perioperative outcomes in regard to intraoperative complications, surgical site infection, and readmission rates when comparing TaTME to laparoscopic TME, but a recent meta-analysis found significantly shorter length of stay in patients undergoing TaTME.^[21-23]

Anastomotic leakage can result in severe short-term morbidity, but more importantly, leakage is associated with an increased risk of local recurrence and reduced survival.^[24-27] A wide range of anastomotic leak rates have been reported, ranging from 5.4% to 16%.^[19,28]

A recent report from our institution by Maykel and colleagues demonstrated a low anastomotic leakage rate of 3.8%, suggesting an advantage to the double purse string technique.^[29]  A large meta-analysis including 2446 TaTME cases found an anastomotic leak rate of 6.8% (95% CI 5.2% – 8.9%),^[30] which is comparable to that of the laparoscopic and open groups in the ALaCaRT trial.^[31]

Intraoperative Visceral Injury

Urethral injury in male patients has been recognized as a particular intraoperative complication in TaTME. There is a slight, but real, increase incidence of urethral injury, particularly at the post-prostatic urethra. Risk factors include surgeon inexperience, anteriorly located tumors, previous pelvic radiation, and patients with prostatic hypertrophy or history of prostatectomy.^[14]

Rates of reported intraoperative urethral injury range from 0% to 6.7% described in an early small series by Rouanet et al.^[6] A recent meta-analysis found an incidence of 0.3%,^[30] and a case series of 34 urethral injuries during TaTME were found to occur in the surgeon’s early experience (during the first 8 cases).^[32] Most injuries were identified and repaired intraoperatively without an increase in conversion rate. 

In female patients, vaginal perforation is of concern during anterior dissection and can result in a rectovaginal fistula. The rate of vaginal perforation has been reported at a rate of 0.3% – 0.4% during TaTME.^[30,33]  These injuries can typically be repaired with a simple suture repair when identified intraoperatively.^[34] Care must also be taken to avoid incorporating the posterior vaginal wall during the creation of the anastomosis. 

Carbon Dioxide Embolism

Carbon dioxide embolism (CDE) is a rare but potentially lethal intraoperative occurrence in TaTME due to high CO₂ insufflation in a small surgical space, risk of venous injury due to wrong plane surgery, and lower venous pressure in the rectal vessels with Trendelenburg position.^[35]

Harnsberger and colleagues reported 3 cases of 80 total at our institution, resulting in an abrupt decrease in end-tidal CO₂, blood oxygenation, and blood pressure (BP) consistent with CDE during the transanal portion of the dissection.^[36] With release of pneumopelvis, hemodynamic support, and patient positioning in the Trendelenburg position with left side down, all patients recovered within 10 minutes without intraoperative or postoperative sequelae.

The rate of CDE was reported at 0.4% in the international registry, with 2 patients requiring cardiopulmonary resuscitation, however, there was no mortality.^[37] Surgeons should be prepared to recognize and manage CDE during TaTME and should speak to their anesthesia colleagues of this rare risk prior to initiating pneumopelvis. 

Specimen Quality

With better visualization of the TME dissection plane in the distal pelvis, TaTME has enabled a more accurate oncologic resection, reflected in the quality of the TME specimen and decreased positive distal and circumferential resection margin rates (DRM and CRM).^[38] These factors have been combined into a composite marker for optimal pathology as a surrogate for surgical quality in recent randomized controlled trials comparing laparoscopic with open TME.^[31,39]

The ALACART (Australasian Laparoscopic Cancer of the Rectum) and ACOSOG-Z6051 (American College of Surgeons Oncology Group) trials reported optimal pathology rates of 82% for laparoscopic groups and 87% to 89% for the open groups.^[31,39]

The International TaTME registry reported a 91.6% composite endpoint with 4% CRM positivity, 1% DRM positivity, and a complete or near complete TME specimen in 80.9% and 10.3% respectively.^[40] A European multicenter cohort with a high proportion of complex rectal cancers, reported an optimal pathology of 86% with an acceptable R1 rate of 8%.^[40]

Our institution  recently reported a 95% rate of optimal pathology with 98.7% complete/near complete specimen, 0% DRM positivity, and 5.1% CRM positivity, and no rectal perforations.^[29]  A recent multicenter analysis comparing consecutive patients undergoing TaTME for rectal cancer with a historic laparoscopic cohort demonstrated that the composite endpoint difference of over 10% between the transanal technique (89.4%) and laparoscopic technique (75.3%).^[41]

A systematic review from Ma and colleagues confirmed these findings with the TaTME group demonstrating higher rate of complete mesorectal specimens, larger CRM, and lower rates of positive CRM.^[21] TaTME enables comparable and possibly improved TME specimen quality with lower DRM and CRM positive rates.

Oncologic Outcomes

Locoregional recurrence

Early TaTME reports reported favorable rates of local and distant disease recurrence, ranging from 1.7 to 7.9% and 12 to 23.4%, respectively.^[42-46] In 2019, Wasmuth et al. published Norwegian data describing 157 patients undergoing TaTME with an alarmingly high local recurrence rate (LR) of 11.6% compared to the national local recurrence rate of 2.4% in the Norwegian registry (NCCR)).^[47]

Eight local recurrences presented in a rapid, multifocal pattern along the pelvic side wall. This led to a moratorium on the use of TaTME in Norway as these findings raised concerns that pneumopelvis during dissection could result in tumor seeding and adverse patient outcomes.^[48,49] 

Van Oostendorp et al. also reported higher LR at 10% after TaTME during a structured training pathway for TaTME implementation.^[50] They described a cohort of patients early in the learning curve (defined as first 10 cases) with a median follow up of 21.9 months. Eight of 12 local recurrences demonstrated multifocal recurrence, similar to the Norwegian data. Indeed, examining the data closely showed that 4 of 7 contributing Norwegian TaTME centers performed 152 cases (32-57 cases per center) over a 4-year period, with an annual average volume of 9.5 procedures.^[38]

These cases, as highlighted by Seow-En et al, were in the learning curve period, which is currently estimated to be approximately 40-51 cases for TaTME.^[51-54] In addition, the 21% of neoadjuvant chemoradiotherapy (nCRT) was significantly lower than that of the national Norwegian nCRT rate of 39%.^[55]

Despite a comparable rate of positive CRM (5.0%), Van Oostendorp and colleagues found a high rate of early complications, including anastomotic leak (17%).^[50] They found that in addition to pT3 tumors and positive CRM, intraoperative complications and postoperative sepsis were significant predictors of local recurrence, proposing that the technical execution of TaTME, as opposed to the technique itself, may be at the issue. Examining data from a larger cohort from centers with more experience, they found that the rate of recurrence declined with increased institutional experience, with 15% of the initial 10 cases compared to 4.2% of the next 30 cases experiencing LR, then 3.8% onwards.^[50] 

More intermediate- and long-term data have gradually become available regarding this issue (Table 1). Recent studies demonstrate LR rates ranging from 2% to 6.2%. Further, studies focused on low rectal cancer and locally advanced cancer cohorts show that despite CRM positivity exceeding 6%, survival rates are comparable.^[41,56]

Analysis of the International TaTME registry with the largest cohort to date of 2,803 patients found a 2-year LR rate of 4.8% after a median follow up of 24 months, with unifocal LR in 96%.^[57] Independent risk factors for LR from this analysis were threatened resection margin on baseline MRI, male sex, pathologic stage III cancer, and a positive CRM on final histopathology. These findings support the oncologic safety of the TaTME technique with an acceptable 2-year LR rate and a predominantly unifocal LR pattern. 

Disease-Free Survival and Overall Survival

Several studies have reported disease-free survival (DFS) at 2 years to be between 77% and 92% (Table 1).  Recent analysis from the International TaTME Registry reported 2-year DFS and OS rates of 77% and 92%, respectively.^[57] A recent propensity-matched cohort by Manchon-Walsh et al. comparing laparoscopic and robotic TME with TaTME demonstrated similar 2-year disease-free survival rates.^[58]

Functional Outcomes

With increased experience and good survival rates for patients with rectal cancer, quality of life (QoL) and outcomes in regard to bowel function, urogenital and sexual function are becoming more significant. “Low anterior resection syndrome” describes a group of symptoms, including diarrhea, fecal urgency and frequency, incomplete emptying, and incontinence, that occurs after rectal resection. Bowel function and continence depend on adequate sphincter preservation and length of preserved rectum.

TaTME permits more patients with low- and mid- rectal tumors to undergo a primary anastomosis to maintain intestinal continuity and avoid a permanent stoma in patients who may otherwise require an abdominoperineal resection due to low tumor height or locally advanced disease. Consequently, the lack of stoma may improve QoL but at the cost of pelvic function. Data regarding functional outcomes after TaTME is limited but largely demonstrate no difference in functional outcomes and QoL when compared to laparoscopic TME.^[59,60]

Bowel function has been shown to decrease shortly after resection with gradual return to close to preoperative quality 6-12 months after surgery, but many patients continue to suffer from LARS of varying degree with reported rates as high as 80%.^[61] However, Keller et al. reported improved QoL after TaTME, with urinary and emotional function after 1 year compared to preoperative levels with stable outcomes in fecal incontinence, major LARS, and sexual function.^[62] This study also found longer perineal operating times were associated with worse LARS.

Despite concerns of increased rates of urologic dysfunction after TaTME, several small studies have found no difference in the International Prostate Symptom Score (IPSS) scores.^[63-65] Foo et al. found that men complained of worse erectile function immediately postoperatively but function returned to baseline after 6 months.^[66] There was no difference in IPSS scores at 3 months and 6 months after surgery.  Current data remains very heterogenous and more research is essential for surgeons and patients to engage in a more developed informed discussion.

Current Challenges and Controversies

TaTME is technically challenging technique with a steep learning curve. With early success and rapid global adoption without regulation, TaTME has been criticized for oncologic inferiority and adverse operative complications.^[52] A national moratorium for TaTME in Norway and abandonment or suspension of the technique in other countries has prompted international collaborations and registries and further analysis of its steep learning curve. Koedam et al. noted a significant reduction in postoperative complications and anastomotic leak rate after the first 40 cases.^[52]

Lee and colleagues determined that 45 to 50 cases are required for surgeons to attain proficiency.^[53] At our institution, Maykel et al. published an early series that outlined the steps to successfully and safely initiate and adopt a TaTME program, highlighting a comprehensive training program and a coordinated team approach.^[67] This novel approach requires the surgeon to master the anatomy as seen from below, which is different from the anatomy traditionally seen transabdominally.^[68-70]

This can cause disorientation with dissection into incorrect planes which can lead to urethral and vaginal injuries. Guidance statements on TaTME have been published by the ESCP (European Society of Coloproctology), St. Gallen Colorectal Consensus Expert Group, CaTaCO (Canadian TaTME expert collaboration).^[16,34,71]

All guidelines agree on a formal structured training program consisting of cadaveric training, team training, careful initial case selection, and  mentoring/proctoring with an expert surgeon until proficiency is obtained.^[72] 

Additionally, there is consensus that challenging cases, such as T4 tumors, prior pelvic irradiation, prostate resection, or other complex surgery should be reserved for expert centers.^[16] Expert centers are defined as those with experienced surgeons beyond the learning curve, multidisciplinary support, excellent outcomes as compared with registry data, with a minimum caseload of 25-30 cases per year.^[16] Guidelines also include prospectively collected pathologic and oncologic TaTME data with participation in regional/national registries. 

Recent results from the Netherlands demonstrate excellent pathologic and intraoperative outcomes for the initial 10 TaTME cases after implementation of a national structured training pathway.^[73] However, the authors noted substantial morbidity even within a structured pathway, reflecting the steep learning curve. Initially, the Dutch TaTME cohort demonstrated a high LR rate of 10% with multifocal LR.^[50] With increased experience, the larger Dutch cohort demonstrated a lower LR rate of 5.6% and decreased to 4% after excluding the initial 10 cases at each center.^[50]

The higher LR rate of the initial experience was attributed to the technical problems of the early learning curve. Early adoption cases should focus on benign diseases such as carpeting villous tumors or inflammatory bowel disease as well as female patients who are not at risk for urethral injury.  Features of TaTME that may account for multifocal recurrence that was seen in early cases may be due to tumor spillage with an inadequate transanal purse string or omitting rectal washout with high insufflation pressures.^[57]

Although the exact cause of multifocal recurrence has yet to be demonstrated, all sites in the ongoing COLOR III trial have been instructed to reinforce the purse-string with a second running suture after the rectal division and perform a second washout.^[50,74] Several studies hope to better elucidate the question of local recurrence, including the North American TaTME trial, COLOR III, GRECCAR 11, and Italian TaTME trial (clinicaltrials.gov).^[75,76]

Conclusion

TaTME is a challenging and complex technique with the potential of improving surgeon capability and patient outcomes for cancers of the mid to low rectum. In the hands of experienced surgeons, the technique has a lower conversion rate, results in more complete pathologic specimen, and shares comparable oncologic and functional outcomes when compared to the conventional “top-down” abdominal approach.

Recent expert consensus statements provide guidelines on structured training paradigms for implementation and adoption of TaTME. Due to its steep learning curve, TaTME is moving toward centralization of cases at tertiary referral centers with high volume and baseline expertise. Histopathologic and oncologic TaTME data should be collected prospectively, and centers should participate in regional/national registries to compare with other experienced centers to monitor and optimize outcomes. Results from ongoing prospective, randomized trials such as COLOR III will help define the utility of this innovative and valuable technique moving forward. 

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