Management of Local Recurrences
Local recurrence after rectal cancer (RC) treatment is associated with patient morbidity and impaired quality of life. Local recurrence rates have decreased from 30% to 5-10% with the adoption of total mesorectal excision (TME) as the operative standard for rectal cancer and improvement in neoadjuvant therapy methods.The incidence of local recurrence is 1% for T1-T2 tumors, 15% for T3-4 tumors, and 12-24% when the circumferential margin (CRM) is involved. Most local recurrences occur within 3 years.Local recurrence is a consideration for monitoring and management after all rectal cancer treatment options including TME, local excision, and non-operative “watch and wait” surveillance after a clinical complete (cCR) response to neoadjuvant therapy. Frequent endoscopic and imaging surveillance for regrowths are essential components of the nonoperative rectal cancer follow-up strategy.
Patients with local recurrence may present with rectal bleeding, change in bowel habits, or pelvic pain. Others may be asymptomatic with local recurrence suggested by an elevated CEA or identified at surveillance endoscopy or surveillance imaging. Incomplete TME and positive surgical margins are risk factors for local recurrence. Other risk factors include male gender, low rectal location, omission of chemoradiotherapy for locally advanced disease, poor response to neoadjuvant therapy, T4 stage, N2 stage, obstruction, perforation, positive extra-mesorectal (pelvic side-wall) lymph nodes, lymphovascular invasion, poorly differentiated tumors, and surgeons who perform less than 20 rectal cancer resections per year.
TME graded as complete with an intact mesorectal fascia propria envelope and negative circumferential margins (CRM) is associated with decreased rectal cancer recurrence rates. Cancers of the low rectum are associated with higher rates of local recurrence, possibly because of more aggressive tumor biology and/or because of more complex anatomy deep in the pelvis that makes R0 resection for locally advanced neoplasia more difficult in this location. It is important not to “cone down” dissecting through the mesorectum to the distal margin during a low anterior resection and to deliver a cylindrical specimen without an anorectal “waist” during an APR. TME that includes the levator pelvic floor muscle is referred to as the extralevator APR. Studies evaluating extralevator or tailored (partially extralevator depending on tumor relationship to levator) APR vs standard APR suggest that extralevator or tailored APR may allow R0 resection for locally advanced low rectal cancers not amenable to a sphincter-saving approach.
Dissection of the lower rectum and obtaining uninvolved CRMs with a transabdominal approach for sphincter-sparing TME may be particularly challenging in an obese male with an irradiated pelvis. Facilitating the transabdominal TME for a low rectal cancer by conducting part of the TME from a transanal approach may potentially allow a better opportunity for an R0 resection. This option is referred to as transabdominal transanal (TATA) TME when the transanal part of the operation is done by an open approach, or transanal TME (TaTME) when the transanal part of the operation is done laparoscopic or robotic. The shorter distance to the CRM with enhanced vision and direct visualization of the distal margin allowed by TATA and TaTME potentially offers more accurate distal dissection, and avoids mesorectal coning with lower positive CRMs, especially for male patients with a narrow pelvis. The adoption of TaTME is limited by a steep learning curve with increased risk of urethral injuries and requires advanced skill sets preceded by structured training. It is, therefore, not currently considered standard of care. Recent advances in MIS imaging may allow the same enhanced vision advantages with the transabdominal approach. Studies comparing TaTME with laparoscopic and robotic transabdominal TME are currently in progress.
Locally recurrent rectal cancer is managed in a multidisciplinary setting (Figure 1).
When local recurrence is identified, colonoscopy is recommended for biopsy and to search for metachronous neoplasia. If the tumor is extraluminal, endoscopic ultrasound or computed tomography (CT) may allow guided biopsy before treatment. While tissue confirmation of tumor recurrence may direct treatment options, there may not be imaging-guided windows for biopsy and false negative biopsies are not uncommon. In these cases, clinical acumen is warranted. MRI and positron emission topography (PET)-CT imaging may be required for clinical diagnosis, exclusion of metastatic disease, and for surgical planning. A rising CEA, increasing size on sequential imaging, and PET evidence of neoplasia may suggest recurrent cancer even with negative biopsy. MRI is essential for the detailed assessment of local recurrence resectability and for operative planning. For patients with a cCR in a nonoperative management program, 90% of rectal wall regrowths are identified by surveillance endoscopy and/or MRI.
When planning treatment of local recurrence, it is imperative to gather and review records of the initial presentation with relevant CT scans and MRI (Figures 2-3).
Previous medical and radiation oncology records should also be reviewed to assess neoadjuvant or adjuvant therapies already delivered and patient response to therapies. The operative report should be evaluated for clues on close margins or intraoperative challenges. The post-operative pathology report should be carefully reviewed for intestinal and circumferential margins, TME grade, and histological markers of recurrence risk such as lymphovascular invasion, histologic grade, and number of positive lymph nodes.
Surgeons participating in the care of patients with locally recurrent rectal cancer should have experience with exenterative anterior, lateral, and posterior pelvic compartment resections.(Figure 4) Exenterative surgery for locally recurrent rectal cancer is extra-TME by definition and more complicated than exenteration for primary tumors. When compared to pelvic exenteration for primary tumors, exenteration for local recurrence is associated with lower rates of R0 resection, longer operative times, and lower median overall survival.
At the multidisciplinary clinic visit, the patient should be assessed for pain, neurological dysfunction, evidence of lower extremity swelling, assessment of sphincter function, and the relationship of the tumor to the anal sphincter, vagina, or prostate. Current performance status should be evaluated to determine ability to tolerate major surgery and prehabilitation should be considered, especially for the elderly. Nutritional status should be optimized and may require a dietitian consult. If recurrent cancer is adherent to prostate or bladder, a frank discussion of urostomy and loss of sexual function is required. For women with vaginal involvement, the importance of preserving vaginal sexual activity should be ascertained. Consultations with urology, gynecology, plastic surgery, neurosurgery, and orthopedic surgery are arranged as indicated. Tumors located in the central compartment at the anastomosis, or involving urogynecologic structures are more often amenable to R0 resection than those involving lateral compartment iliac vessels and nerves deep to the piriformis fascia, or posterior compartment recurrence adherent to the sacrum.
Patients with local recurrence should be presented in a multidisciplinary tumor board conference setting after imaging has been completed. Multidisciplinary management principles include:
1. Imaging to search for distant metastatic disease because pelvic exenteration is not recommended for patients with distant metastases except in selected cases depending on patient age, performance status, extent of metastatic disease, timeframe of recurrence, and symptoms.
3. R0 resection of local recurrence is the best predictor of survival and is defined by en bloc resection of the recurrent tumor, adherent adjacent organs and other resectable structures that enable macroscopic and microscopic margins to be obtained. Intraoperative radiation therapy (IORT) may be a useful adjunct to surgery where available. Patients requiring complex challenging resections or IORT may be referred to specialty centers with relevant resources and expertise.
At the time of surgery, the patient is placed in the semi-lithotomy position in preparation for a combined transabdominal and perineal approach with perineal reconstruction when indicated for low rectal tumor recurrences. Cystoscopy with ureteral stents are usually recommended. Operating in a previously dissected and irradiated pelvis is a technical challenge. It is important to gain proximal and distal control of organs, vessels, and nerves before approaching the relevant pelvic compartments. Initial abdominal exploration for metastatic disease is done and lesions suspicious of cancer are biopsied and sent for frozen section analysis. If positive, palliative resection is considered while minimizing operative morbidity. Abdominoperineal resection is the operation of choice when the tumor invades the external sphincter complex and this operation often leaves large irradiated wounds that may require complex closure techniques. Myocutaneous flaps may allow perineal wound closure and vaginal reconstruction for many of these patients.
The final specimen should be oriented, ideally with the aid of a pathologist. Marking sutures should be placed for identification of areas that may have close margins with further frozen sections and further resection guided by these maneuvers when possible. If wider margins are not possible, then IORT may be considered where available.
Distant metastatic disease occurs in up to 53% patients at 5 years following resection of local recurrence. Adjuvant chemotherapy may be recommended depending on what neoadjuvant therapy strategy was previously administered. While recurrent rectal cancer studies include a heterogeneous group of patients with variable selection processes, R0 resection rates in specialist exenteration centers are currently 55-58% with 5-year survival up to 40-50% and re-recurrence in 55%.Multivariate analysis of 1184 patients in 27 specialist centers revealed that R0 status and bone resection (when required) were significant determinants of long-term survival.
Palliation is an important part of multidisciplinary rectal cancer treatment, particularly for those with symptomatic local recurrences and metastatic disease. Patients may be candidates for external beam or focused cyberknife radiation to palliate bleeding, obstruction, and pain. Diverting colostomy may be an important intervention for potentially curable obstructing rectal cancers prior to instituting neoadjuvant therapy, and may also be effective in palliative management of pain, defecatory dysfunction, and/or obstruction in patients with unresectable locally recurrent or metastatic disease. Chemotherapy can prolong survival and decrease symptoms for some patients. Goals of care and palliative medicine should be discussed in a multidisciplinary setting that includes palliative medicine specialists in a pathway that may ultimately lead to hospice care.
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