Rectal Cancer: Local Excision

Introduction

Local excision for a rectal tumor dates back to the early 1800s, with a report by Dr. Jacques Lisfranc describing excision of a benign rectal mass in the lower rectum. ^[1]  This approach is ideal for lesions within 8cm from the anal verge, <3cm in size and occupying <40% of the rectal circumference ^[2].

Tumors located more proximally in the rectum can be more challenging, so the development of the “Transanal endoscopic microsurgery” (TEM) technique by Buess was a significant advance to overcome some of these anatomic constraints ^[3].  In 2010, Atallah described the transanal use of a single port laparoscopic platform with the use of insufflation to perform transanal minimally invasive surgery (TAMIS) which has replaced the TEM procedure and allowed for the utilization of standard laparoscopic instruments with which surgeons are familiar ^[4].

Patient Selection

The local excision technique was initially described for benign tumors in the rectum and was an alternative to a proctectomy.  Local excision allowed the patient to avoid major abdominal surgery and could be curative, provided that negative margins could be obtained and there was no invasive cancer.  Morson et al in 1977 at St. Mark’s Hospital first described the local excision technique for a known rectal cancer and reported a low rate of local recurrence after excision with negative margins ^[5]. 

In contrast to local excision, the standard surgical treatment for rectal cancer usually includes the principles of total mesorectal excision (TME) initially described by Dr. Heald ^[6].  This is still the gold standard in surgical care for rectal cancer, but rectal cancer care has evolved significantly with the advent of multidisciplinary approaches to rectal cancer care which includes chemotherapy and radiation.  Management of locally advanced rectal cancer is to be discussed elsewhere and is a rapidly evolving field.

Patient selection is critical when patients are being considered for local excision surgery.  Digital rectal examination along with proctoscopy is vital to assess tumor character, fixation, and relation to the anorectal muscular ring or sphincter complex.  Staging evaluation is still critical in the initial diagnosis, including a baseline carcinoembryonic antigen level (CEA), computed tomography (CT) of the chest, abdomen and pelvis to determine any metastatic spread and magnetic resonance imaging (MRI) or transrectal ultrasound (TRUS) to assess local tumor staging.

The rectal cancer protocol MRI is an important tool to help differentiate tumors, assessing the relationship to the mesorectal fascia and lymph node status, although certain findings (heterogeneous signal intensity and irregular margins) are usually indicative of lymph node involvement with tumor ^[7].

The MRI is the key for consideration of a local excision technique although may over-stage early T-stage tumors.  The following sections discuss management and outcomes for various stage tumors thought to be suitable for local excision.

T1N0

In general, local excision as a sole definitive treatment for rectal cancer should be reserved for histologically favorable T1 cancers, which by definition are confined to the submucosa.  However, T1 cancers with unfavorable histologic features, such as presence of lymphovascular invasion, poor differentiation, tumor budding, should be strongly considered for proctectomy given the risk of lymph node metastasis.

Adherence to these strict criteria may produce equivalent survival for local excision when compared to radical surgery.  An analysis of retrospective data from the Surveillance, Epidemiology and End Results (SEER) database reported that local excision of a T1 rectal cancer produced similar cancer-specific survival when compared to radical surgery ^[8].

Two meta-analyses, comparing local excision and radical surgery for T1 rectal cancer demonstrated similar 5-year overall survival when comparing outcomes of the TEM subgroup and proctectomy ^{[9, 10]}.  If a patient undergoes local excision and final pathology unexpectedly reveals high risk features, patients should be considered for completion proctectomy or adjuvant chemoradiotherapy.

Predicting Lymph Node Metastasis

The ideal candidate for local excision is a patient who has a primary tumor with favorable histology, that can be excised completely with negative margins and has no lymph node metastasis.  In this ideal patient, local excision can be curative. However, our ability to predict lymph node metastasis is not ideal, and occult lymph node metastases may be the primary driver of the higher local recurrence rates observed following local excision as compared to radical surgery.  Estimates of lymph node status in rectal cancer patients thus dramatically affects treatment recommendations. 

Depth of Invasion

T1 lesions are further classified according to the depth of invasion of the tumor by dividing the submucosal layer into thirds according to Kikuchi ^[11].  There was an incremental increase in risk of lymph node metastasis and/or local recurrences with a deeper depth of invasion.  The risk of lymph node metastasis is 3% for lesions invading the superficial 1/3 of the submucosa (SM1), but it rises to 23% for deeply invading lesions (SM3) and therefore local excision should be reserved for superficial or middle lesions for the best curative and oncologic results ^[12-14].  Tumors with a depth invading to the SM3 level were found to be similar to T2 rectal cancers in relation to lymph node metastasis and local recurrence rates. 

Unfortunately, SM level can only be accurately assessed after excision of the tumor.  Although occasionally SM level can be assessed in a routine polypectomy specimen, this is relatively uncommon, as there is the need for a significant portion of the submucosa within the resected specimen in order to define the deepest border of the submucosa. Therefore, SM level calculation is typically only useful after local excision to make decisions regarding recommendations for completion proctectomy or adjuvant chemoradiotherapy.

Lymphovascular Invasion and Poor Differentiation

Lymphovascular invasion is found to be the most consistent histologic feature associated with metastatic disease.  Chang retrospectively reviewed 943 patients with pT1 or pT2 rectal cancers at a single institution and found lymphovascular invasion was the variable that was most strongly associated with the risk of lymph node metastasis, with an odds ratio of 11.5 and risk of 68.8% ^[15].

Lymphovascular invasion has recently been reported to be associated with systemic recurrence in rectal cancer patients, which is less amenable to curative surgical interventions and associated with reduced overall survival ^{[16, 17]}.  Hogan et al found that lymphovascular invasion in rectal cancer patients portended an increase in systemic recurrence and therefore an adverse effect on survival ^[18].

In addition, poor differentiation on histology is associated with lymph node metastasis in rectal cancer ^{[19, 20]}.  Bosch et al performed a meta-analysis of 17 studies and further confirmed that poor differentiation, amongst other adverse histologic findings, is a strong predictor of lymph node metastasis with a relative risk of 4.9 (95% confidence interval 3.3-6.9) ^[21].

Tumor Budding

Tumor budding was initially described by Hase in 1993 and defined as small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion ^[22].  A review of 663 patients who underwent curative resection of colorectal cancer found that tumors with substantial budding had more aggressive behavior than tumors without budding.  Initially reported primarily in the Japanese literature as a predictor and prognostic indicator of lymph node metastasis ^{[23, 24]}, more recent reports from Western centers have supported this concept ^{[21, 25]}.

It has now been adopted in the reporting system and is well-established as an independent adverse prognostic factor in colorectal carcinoma.  Consensus statements and recommendations by the International Tumor Budding Consensus Conference (ITBCC) that support tumor budding as an independent predictor of lymph node metastasis in T1 colorectal cancer.

T2

To date, local excision has been a plausible option in early rectal cancers, namely T1 tumors, but what about T2 lesions?  Proctectomy for patients with T2 rectal cancers is associated with high cure rates at the cost of high morbidity, risk of permanent colostomy and significant impairment to anorectal, sexual and urinary function with an associated effect on quality of life ^{[26, 27]}.

However, the standard recommendation for T2 lesions remains radical resection due to the high risk of lymph node metastases, unless patient comorbidities are prohibitive, or the patient refuses radical surgery and/or the possibility of a colostomy.  Locoregional recurrence rates for T2 tumors after local excision alone are unacceptably high, ranging from 13-30%, which may be partially due to the 30-40% incidence of occult nodal involvement ^{[28, 29]}.

However, recent evidence suggests that local excision with adjuvant chemoradiotherapy may be effective in treating occult nodal disease and minimize recurrence ^{[30, 31]}.

Techniques

A thorough surgical history and physical examination including bowel function and continence are important prior to scheduling.   The examination includes a digital rectal examination along with office proctoscopy to determine the location and characteristics of the mass.  Standard transanal excision technique can be a viable option if the rectal cancer is palpable with digital examination, and specifically if the top of the mass can be palpated.

Optimal visualization during surgery is imperative so a mechanical bowel preparation is recommended in most circumstances, but a simple enema preparation may suffice in the appropriate patient.  Preoperative intravenous antibiotics should be given within one hour of the start of the surgery.

General anesthesia is most commonly used for these cases, although spinal anesthesia and MAC sedation can also be viable options in the appropriate patient.  Patient positioning is based on the location of the tumor and surgeon preference. Many surgeons would want the tumor in the dependent position.  For known or strongly suspected cancer, a full thickness dissection is typically performed.  Closure of the defect should be completed in a transverse fashion to avoid stricture formation.  If closure is not possible, and the peritoneal cavity is intact, then closure by secondary intention is reasonable.

TAMIS was first introduced in 2009 as an alternative to TEM, offering similar visibility and versatility but at a significant cost advantage ^[4].  Dissection can be performed in multiple quadrants and this technique uses a flexible, disposable single port minimally invasive platform placed transanally along with insufflation and laparoscopic tools.  Insufflation occurs and the tumor marking occurs in a similar way using cautery and closure of the defect occurs with varying techniques ^[32].

If the tumor is near the top of the anal sphincter, a hybrid approach using TAMIS and transanal approaches may be necessary.  If intraperitoneal entry occurs or is suspected during a TAMIS procedure, laparoscopic assistance may be necessary for closure of the defect and to perform pneumatic leak testing, as one would perform following colorectal anastomosis.

Complications

Each of the described techniques for local excision of early distal rectal cancers has limitations.  Incomplete resection, conversion to an alternative approach, or the need for staged procedures represent a few of the more common limitations.  These events are more likely to occur if the tumor is too bulky or if the working environment/space is too tight, incomplete visualization of the entire tumor due to a fold, uncontrolled bleeding occurs or poor bowel preparation.

Overall, the complication rate for local excision, regardless of the technical approach, is lower than for radical surgery ^[33].  Common complications after local excision include urinary retention/urinary tract infections, bleeding (up to 5%), infection/abscess and other gastrointestinal complaints.  Uncommon complications include wound infections, thromboembolic events, rectal strictures or rectovaginal fistulas.

The most common complication with local excision is post-surgical urinary retention.  This can occur up to 5% of patients and secondary to pressure on the urethra, anal stretch, edema and pain ^[34].  This is usually self-limited and treated by either self-catheterization or placement of an indwelling catheter. 

Oncologic Results

Local excision is an acceptable oncologic treatment strategy for patients with T1 rectal cancers, and local excision with chemoradiation treatment has gained some interest and can be an acceptable oncologic treatment for certain patients with T2 distal rectal cancers.  

T1 Cancer

Since the first report of local excision as an acceptable alternative to radical resection, local excision without additional therapy has been offered as a treatment alternative for early distal T1 tumors ^[6].  Approximately 15% of rectal cancers present at Stage I, and thus local excision is a viable oncologic approach in appropriately selected patients with favorable clinical and histological features.  Local excision can also be viewed as a palliative treatment for patients with more advanced disease who are medically unfit for radical surgery.

The main drawback of local excision as curative therapy is the inability to excise and accurately stage mesorectal lymph nodes.  T1 rectal tumors have a 6-11% risk of nodal metastasis overall, pending additional histologic information ^[28].

Criteria for local excision include well to moderately differentiated T1 cancer, the absence of lymphovascular or perineural invasion, and tumors less than 3 cm in diameter occupying less than one-third of the circumference of the bowel lumen ^[38].

It has been shown that a positive margin following local excision of a T1 rectal cancer is associated with a higher risk of recurrence and concomitant lower 5-year overall survival ^[35].  Therefore, optimal surgical technique is imperative to achieve a good oncologic outcome. 

As noted previously, this has been a substantial problem in prior trials of local excision. Even using more modern techniques, achieving negative margins can be challenging. Prospectively collected data from a 21-center collaborative in the United Kingdom regarding 424 patients undergoing TEM +/- adjuvant/neoadjuvant radiotherapy revealed that positive margins were found in in 11%, 23% and 42% of patients with pT1, pT2 and pT3 tumors.  These studies have shown that to minimize the risk of local recurrence, it is advisable to limit local excision to T1 rectal cancers with favorable histology as mentioned previously ^{[18, 21]}.

T2 Cancer

The significant rates of metastatic nodal disease with T2 rectal cancers have swayed most surgeons from treating T2 rectal cancers with local excision alone as this approach can lead to local recurrence rates of 10-66%^[51].  High rates of local failure and compromise in survival outcomes have been shown, with 5-year local recurrence rates of 47% in patients undergoing local excision alone compared to 6% with proctectomy and overall survival of 65% versus 81%, respectively ^[37].

Despite these sobering numbers, there has been increasing emphasis on organ preservation techniques. In fact, some surgeons have recommended expanding the indications for local excision to include some T2 rectal cancers. 

Data and evidence from the Surveillance, Epidemiology and End Results program reveal that more than 20% of patients with T2 cancer are being treated by local excision, although those treated with local excision alone had a suboptimal overall survival ^[38].  Recent clinical trials have evaluated local excision combined with neoadjuvant or adjuvant treatment in T2 cancers with the hope of improving outcomes and expanding eligibility for organ-sparing surgery.

Local Excision and Adjuvant Therapy

The Cancer and Leukemia Group B 8984 trial (CALGB 8984) compared oncologic outcomes in patients with T1 rectal cancer treated with local excision alone and T2 rectal cancer treated with local excision followed by adjuvant chemoradiotherapy ^[35].  They found that despite adjuvant therapy, the T2 group experienced worse 10-year overall survival and disease-free survival and were at higher risk of local recurrence (18% vs. 8%).

A systematic review by Cutting et al found local recurrence rates of 6% for T1, 14% for T2, and 34% for T3 rectal cancers ^[39].  These studies suggest that adjuvant therapy after local excision for T2 or greater rectal cancers is inferior to radical surgery, but better than local excision alone.

Neoadjuvant Therapy and Local Excision

Traditionally, locally advanced rectal cancer was treated with chemoradiotherapy followed by radical surgery with the benefit of tumor downsizing and improvement in local recurrence rates in large randomized controlled trials ^{[40, 41]}.  It has been shown that up to 30% of patients will experience a complete pathologic response after neoadjuvant chemoradiation ^[42].

In the hope that occult tumor in mesorectal nodes could be sterilized with neoadjuvant chemoradiotherapy, some surgeons explored the concept of local excision following neoadjuvant therapy in select patients.  Several studies including The American College of Surgeons Oncology Group Z6041 study ^[43], Lezoche ^[44], GRECCAR 2 ^[45] and the recently published CARTS study ^[46] are under constant review and detail that one of the major downsides of local excision following neoadjuvant radiotherapy is the problem of wound healing in an irradiated field. 

Quality of Life

One of the goals of organ preservation with local excision is better functional outcomes with a better quality of life.  Although resection of the rectal wall can have functional consequences, several studies have shown that those patients with early rectal cancers who undergo local excision compared with those who undergo radical resection, have a better quality of life and better bowel function overall ^{[47, 48, 49]}.

Salvage Surgery

Population-based studies have shown that the treatment of early distal rectal cancers by various local excision techniques have more than doubled over the last 2 decades ^[38].  This is likely due to advancements in local excision surgical platforms, patient preference and publication of outcome data.  Local recurrence is the most common pattern of failure, ranging from 20-30% ^{[33, 36]}.

When patients develop a local recurrence, what surgical options are available and what are the prognosis and long-term oncologic outcomes?  Bikhchandani et al reported an R0 resection rate of 93% on 27 patients who underwent multi-modal salvage surgery for local recurrence of rectal cancer after local excision ^[50] but found that the majority of re-recurrences were distant metastases. 

The practice of local excision seems to exchange the increased risk of disease recurrence for the benefit of improved function and sphincter preservation.  It is imperative to counsel patients regarding the oncologic risks of local excision and explain that salvage therapy is not always associated with good outcome.

Conclusion

Local excision alone as definitive treatment can be offered to select patients with early T1 rectal cancers in the absence of adverse histopathologic features, such as poor differentiation, lymphovascular invasion, tumor budding, or close margins.  Patients with low risk T2 tumor should be considered for local excision only in the context of palliative intent or enrolment in a clinical trial.

Salvage surgery for local recurrence in those treated initially by local excision is possible in some patients, but oncologic results appear to be inferior to those that would be obtained by proctectomy at initial diagnosis. All patients managed with organ preservation usually undergo intensive post-treatment multimodality surveillance, as identifying local failure early will lead to improved outcomes.

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