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Surgical Management of Patients with Rectal Cancer: LAR/APR

Oncology
Surgery
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Indications

Management of rectal cancer requires a multidisciplinary approach, which includes: oncology, pathology, radiation oncology, radiology, genetics, ostomy consultation and colorectal surgery[1]. In practice, the location of a rectal cancer is most commonly assessed by the distance from its distal margin to the anal verge (beginning of the hair-bearing skin)[2,3].
Radical resection of locally advanced rectal cancer is achieved when a wide resection of the cancer is performed with the goal of achieving histologically negative margins, along with total mesorectal excision (TME) with resection of local lymph nodes. In this chapter we focus our discussion on the surgical management of rectal cancer, and thus we will not examine the role of neoadjuvant therapy.  In general, rectal adenocarcinoma of the upper third of the rectum is managed similarly to colon cancer with upfront surgical resection, whereas locally advanced cancers of the mid- and low rectum require a multidisciplinary approach with chemoradiotherapy and surgery.
Current management of rectal cancer varies depending on tumor characteristics, size and location of the tumor[4] (Figure 1). Locally advanced rectal tumors can be managed with sphincter-sparing resections (low anterior resection; LAR) unless the tumor invades the sphincter complex or is in such close proximity that an appropriate oncologic distal margin cannot be achieved, in which case abdominoperineal resection (APR) is required.
Patients with selected small lower rectal tumors can undergo local excision and achieve survival comparable to APR, with the added benefit of preserving sphincter function. The use of neoadjuvant (preoperative) chemotherapy and radiotherapy allows for tumor regression, and potential for sphincter preservation. In some cases, despite neoadjuvant chemoradiotherapy (CRT), some locally advanced tumors that involve adjacent pelvic organs may require multivisceral resection.
Figure 1. Algorithm for management of rectal cancer
Surgical Management by Stage
Clinical/Pathologic T1N0
Some T1N0 lesions can be effectively managed with polypectomy alone. The goal is to achieve complete en bloc polypectomy, to determine the margin and depth of invasion[5]. If a malignant polyp has poorly differentiated histology, lymphovascular or perineural invasion, intermediate or high tumor budding or submucosal invasion depth higher or equal to 1mm, local staging with positive lymph nodes or large (≥2cm) pedunculated polyps unable to safely resect, endoscopic management alone is insufficient[6].
If endoscopic management is not feasible, ESMO and NCCN guidelines recommend local excision on T1 lesions[7,4], less than 3cm in diameter, with well-differentiated histology, with no lymphovascular or perineural invasion, with clear margins (>3mm), that involve <30 percent of the bowel lumen circumference, and most importantly that are able to comply with frequent postoperative surveillance. Distal T1 lesions can undergo transanal resections[8], while more proximal lesions can be resected using transanal minimally invasive techniques such as TEM (transanal endoscopic microsurgery) or TAMIS (transanal minimally invasive surgery).[9]
Clinical T2N0 and cT1N0 not amenable to local excision
Transabdominal surgery is recommended, due to the high risk of nodal metastases (>10%). Neoadjuvant CRT is not indicated, unless it is decided in multidisciplinary discussions in order to improve the odds of being able to perform a sphincter preserving procedure[10].
For patients that undergo surgery, Postoperative adjuvant therapy is recommended if final pathologic stage is pT3 or pN+[7], although this is associated with worse postoperative function and thus the potential oncologic benefits must be carefully weighed against functional concerns in this setting.
Clinical T3-4, N0-2 or T2, N1-2
If no distant metastases are identified, preoperative CRT or total neoadjuvant therapy (TNT) is indicated before surgery. Benefits include: superior sphincter preservation rate, decreased rate of anastomotic stenosis and improved local control with comparable long-term survival[7].
If distal metastases are identified, individualized management is recommended along with multidisciplinary tumor board discussion[11]. Taking into consideration if metastases are resectable, and if there are symptoms associated with the primary tumor. If metastases are resectable, systemic chemotherapy, followed by a short course of radiotherapy to the primary lesion followed by resection of both primary tumor and metastatic disease[12].

Technical Considerations

In order to achieve curative surgical management, resection of rectal cancer must include achieving histologically negative margins[13], along with total mesorectal excision (TME)[14] and a proper lymph node dissection[15].
Resection Margins
Proximal margins should achieve a minimum of 5cm, in order to remove draining lymphatics. Distal margin varies depending tumor location. For upper rectal tumors, a 5cm distal margin to the tumor is expected. For mid- and low rectal tumors  the minimum negative distal margin is 2cm for LARs with TME, although a 1cm negative distal margin along with TME has been found acceptable in selected patients[16] after neoadjuvant chemoradiation.
Circumferential radial margins (CRMs) are a crucial aspect of rectal cancer resection. A histologic CRM of greater than 1mm is required. A positive CRM has been found to be an independent predictor of local recurrence and inferior survival[17,18].
Vascular Ligation
In order to achieve curative resection, one must remove the blood supply and lymphatics from the origin of the superior rectal artery. Ligation of the IMA distal to the takeoff of the left colic artery at the origin of the superior rectal artery also known as “low tie” should be used routinely [19].
“High tie”, which involves ligating the IMA at its takeoff from the aorta should be used in selected patients when clinically suspicious lymph nodes are present near the IMA or to help with mobilization to achieve a good length and a tension free anastomosis.
“Low tie” has comparable rates of blood loss, operative times, postoperative complications including leaks with the added benefit of preserving sexual and genitourinary function[20].
Lymph Node Dissection
The number of lymph nodes required for accurate staging are 12 lymph nodes[4]. This quality metric has been adopted by the National Comprehensive Cancer Network (NCCN), the American College of Surgeons (ACS) and the American Association of Clinical Oncology (ASCO). Neoadjuvant chemoradiation has been found to reduce the number of lymph nodes that can be retrieved in a specimen[21].
Routine lateral pelvic lymph node dissection is not required if clinically positive lymph nodes are not present in that compartment. Specially after undergoing neoadjuvant chemoradiation for low rectal cancer. If clinically positive lateral lymph nodes are present, ipsilateral pelvic lymph node dissection is indicated[22].
Total Mesorectal Excision
Dissection in the TME plane has been found to preserve autonomic nerves and reduces intraoperative bleeding and the risk of recurrence[23]. TME was also associated with improved local control and better survival [24].
For upper third rectal tumors, curative resection must involve mesorectal excision along with LAR. The mesorectum should be divided at least 5cm below the distal margin of the tumor (a “tumor-specific mesorectal excision”). Tumors that are located in the mid or low rectum, full TME should be performed along with LAR or APR.

Specific Technical Considerations [25]

The initial goal is to identify the posterior plane at the level of the sacral promontory. This allows to identify the superior hemorrhoidal vessels, the ureter and the hypogastric nerve trunks. Sharp dissection should be carried between the visceral and parietal layers of the endopelvic fascia down to the pelvic floor, to facilitate en bloc removal of the rectal cancer and the mesentery, lymphatics and tumor deposits.
By defining the posterior plane, visualization of the lateral mesorectal plane is improved, dissection in this plane will include the division of the middle rectal vessels. During lateral dissection, hypogastric nerve trunks should be identified (posterolateral to the mesorectum and medial to the endopelvic fascia. Injury may cause retrograde ejaculation and impaired bladder accommodation.
For the anterior plane of dissection, one should determine if dissection will occur anterior or posterior to Denonvilliers’ fascia. This should be determined by the location of the tumor. If performing a dissection anterior to Denonvilliers’ fascia, it is important to consider the autonomic nerves that run anterolateral to the dissection.
Circumferential dissection is carried down to the pelvic floor, exposing the rectum at the level of the anorectal ring. In order to accomplish this, the retrorectal fascia must be divided, allowing for adequate mobility to achieve a low anastomosis.

Low Anterior Resection (LAR)

Patients with an invasive cT2-T4 cancer, in which a negative distal margin can be achieved and have adequate anorectal sphincter function should undergo a LAR.
Specific Technical Considerations
Mesenteric mobilization
Regardless of medial to lateral, or lateral to medial mesorectum mobilization, mesenteric mobilization should include dissection of the retromesenteric plane posterior to the superior rectal artery. Injury to the superior hypogastric nerve plexus should be avoided (retrograde ejaculation, erectile dysfunction). The mesocolon in continuity to the mesorectum should be preserved[25].
Left ureter identification
During dissection, the left ureter must be identified. This can be efficiently achieved by identifying the IMA and its proximal branches[25].
Location of tumor and sphincter preserving strategies
For high rectal tumors, with the help of preoperative MRI, one should determine the extent of mesorectal dissection using the relationship with the surrounding structures. Palpation of the tumor during rectal dissection, intraoperative flexible or rigid sigmoidoscopy can be used to confirm location of distal transection. For mid-rectal tumors, mesorectum dissection should continue to the pelvic floor and transection should be aimed at rectal region free of mesorectum.[26]
For low rectal cancers (2-5cm), two techniques can be used. Transabdominal resection followed by transanal mucosectomy above the dentate line can ensure adequate distal margins. This technique allows for preservation of both the internal and external sphincter, and it’s completed with hand-sewn coloanal anastomosis[25].
If the lesion is located within 2cm of the dentate line, an intersphincteric resection can be used. This includes removing the internal sphincter completely or partially. This technique can be considered for patients with good response to neoadjuvant CRT, if patient has a poor response, poorly differentiated histology or risk of external sphincter being involved, an APR should be offered[27].

Abdominoperineal Resection (APR)

Patients with an invasive cT2-T4 cancer who can’t achieve a distal margin of 1cm with a sphincter- sparing procedure, or who have locally advanced low-lying rectal cancer or locally recurrent low- lying rectal cancer should undergo APR[28].
Specific Technical Considerations
Dissection of the distal rectum
Dissection of the elevator muscles should be carried towards the perineal body, by first dividing the puborectalis at the level of the prostate or cervix (Denonvilliers fascia). Dissection continues caudal, dividing the muscle attachments to the rectal longitudinal layer of the muscularis propia and pushing the rectum down. This improves exposure and decreases the risk of anorectal perforation and risk of compromising CRMs[28].
Perineal dissection
A purse string suture can be used to close the anal opening and prevent fecal contamination of the perineal wound. When performing the circumanal skin incision, adequate skin and ischioanal fat margin needs to be achieved for low tumors invading the ischioanal fat[25].
For tumors not involving the ischioanal fat or perineal skin, the complete levator muscle to the insertion of the internal obturator muscle must be included in the specimen, with limited resection of the ischioanal fat and perineal skin[29]. Due to this, primary closure of the perineal wound is possible.
For tumors invading the ischioanal fat and perineal skin, wide margins of perineal skin and ischioanal fat to the ischial tuberosity are included, along with resection of the levator complex to the tendinous insertion on the pelvic side wall, if necessary, from an oncologic standpoint. A large defect is created that requires perineal reconstruction.
Early in the perineal dissection, the anococcygeal ligament is divided posteriorly. Dissection continues in the plane between the fascia propia of the rectum and presacral facia until communicating with the dissection from the transabdominal approach.
Two approaches can be used: the classic extralevator approach: the levator muscles are divided from their lateral pelvic attachments to the obturator internus muscle. For the tailored extralevator approach: the levator muscle is divided in the midportion with an adequate margin around the neoplasm[30].
Continuing the dissection cephalad preserves the fascia propia of the rectum, continuing the TME from the perineal approach.
Perineal Reconstruction
Perineal reconstruction should be considered after extralevator excision and in patients receiving neoadjuvant chemoradiotherapy[31]. Primary closure vs flap closure is still unresolved in the literature as there are relative risks and benefits to each approach and ultimately the decision should be made depending on the extent of perineal excision[32].
Both a randomized trial and a meta-analysis have demonstrated fewer perineal wound complications with pedicled vertical rectus abdominis mycutaneous flaps than with primary closure. A NSQIP study found that patients with flap reconstruction had longer operative times, deeper surgical site infections, more wound dehiscence and reoperations[33].
Use of Diverting Ostomy
A temporary diverting stoma is generally recommended in a low (<5cm) anastomosis, if the patient underwent preoperative pelvic radiation, or if the patient is on immunosuppressive therapy[34]. Ultimately it is at the discretion of the surgeon whether temporary fecal diversion is appropriate, as diversion may minimize the sequela of an anastomotic leak.
Anastomotic leak may lead to delays in adjuvant chemotherapy and can negatively impact survival.  A loop ileostomy is recommended over loop colostomy, due to simplicity at reversal, but important to keep in mind the risk of high stoma output and dehydration[35]. For any ostomy indicated, early involvement of ostomy nursing for perioperative teaching is fundamental.

Postoperative Surgical and Oncological Outcomes

Minimally Invasive Approaches
Minimally invasive rectal cancer surgery should only be performed by surgeons experienced in performing MIS proctectomy with TME. Patients with high-risk circumferential resection margin on preoperative staging, with an acute bowel obstruction or perforation from rectal cancer should generally undergo open surgery[4].
Laparoscopic vs Open Surgery for Rectal Cancer
There is a benefit in short-term perioperative outcomes when using laparoscopic surgery for rectal cancer. Some of these include: decrease in postoperative pain, shorter length of stay, decreased postoperative complications and lower blood transfusion requirement. There are still some concerns about long term oncological outcomes. Pathologic outcomes after laparoscopic resection were under scrutiny after the CLASSIC[36] trial reported a higher CRM in the laparoscopic group (16% vs 14%).
Although not statistically significant, since then the ACOSOG Z6051 trial has failed to show noninferiority of laparoscopic surgery compared to open when using a composite outcome evaluating CRM and TME completeness[37].
The ALaCaRT trial also found fewer patients  undergoing laparoscopic surgery achieve successful resection when compared to the open arm[38]. Along with randomized clinical trials, meta-analyses have found higher rates of incomplete resection in the laparoscopic arms.
Ultimately, current consensus is that laparoscopy can be considered if performed by experienced surgeons with the appropriate technical expertise.[2]
Robotic vs Laparoscopic Surgery for Rectal Cancer
The ROLARR trial compared short term outcomes between robotic and laparoscopic approaches for both LAR and APR. Similar rates of conversion to open, positive CRM, mortality and overall complications were found[39].
The robotic approach was associated with longer operative times and higher hospital costs. A systematic review and meta-analysis confirmed these results, finding similar perioperative outcomes, longer operative times for the robotic approach but lower rats of conversion to open surgery. Despite limited oncologic data on robotic approaches, rate of robotic proctectomies have increased from 3.1 to 26% from 2012 to 2018[40]

Complications

Anastomotic Leak
Anastomotic leak is a major complication after resection for rectal cancer that can have an impact in morbidity, mortality and long-term functional outcomes. There are conflicting results on the impact of anastomotic leaks on local and distant recurrences[41], with a meta-analysis showing higher local recurrence and reduced long-term survival[42]. Anastomotic leak rates range between 3% and 23%, rates vary depending on surgical approach and Institution.
Multiple studies have identified risk factors that increase the risk of developing anastomotic leaks after surgery. Some of these include male sex, longer operative times, higher intraoperative blood loss[43,44].
Perineal Wound Complications
Patients undergoing APR might not have the anastomotic leak risk patients undergoing LAR have. But their risk of perineal wound complications increases. Incidence of wound complications range from 10-40%. Increased BMI (<35), diabetes, smoking and preoperative chemoradiotherapy increase the risk of perineal wound complications, with evidence that perineal wound complications also affect long-term survival[31].
Sexual and Urinary Dysfunction
Pelvic nerve bundles lie in close proximity to the mesorectum. Due to this, there is an increased risk of sexual and urinary dysfunction. Open TME has been associated with urinary dysfunction rates of up to 12% and sexual dysfunction rates between 10-35%. [45]
Laparoscopic approaches have been found to have similar rates of sexual dysfunction when compared to open approach[46]. A prospective series, evaluating sexual and urinary outcomes after robotic and laparoscopic surgery for rectal cancer, found earlier recovery of normal voiding and sexual function after robotic surgery[47]. This is probably related to the improved visualization and increased magnification that robotic surgery allows when dissecting in the pelvis.

Controversies

Management of patients with a complete clinical response to neoadjuvant CRT.
The use of neoadjuvant chemoradiation has been associated with a pathologic complete response (pCR) of up to 20%. Currently, there is no adequate way of identifying patients with a pCR, without evaluating histology after resection[48].
Due to this, radical resection is offered to patients after completing neoadjuvant therapy. Management of patients with complete clinical response (cCR) and the need to undergo radical resection is under question. A big concern is that the correlation between cCR and pCR is poor, and selection of which patients will have pCR cannot be reliably made.
Despite these concerns, a “watch and wait” nonoperative approach is being explored in selected patients who achieve cCR[49]. Studies favoring “watch and wait” include the fact that salvages rate if needed range between 83.8% and 95.45% in patients with recurrence, and current data from the International Watch & Wait database shows 97% of regrowth occurring during the first 2 years was local within the bowel wall[50].
Currently recommendations are to only use “watch and wait” after carefully discussing in highly selected patients who achieve a cCR in an Institution with a protocolized follow-up regimen.

References

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