Management of Local Recurrences

Local recurrence has always been a major problem after rectal cancer (RC) treatment, and decreasing risk of local recurrence has been the impetus for adoption of multi-modality therapy and promoting better quality surgery since the 1980’s. With high-quality modern treatment, rates of local recurrence have decreased from about 30% to 5-10%, and most local recurrences occur within 3 years.[1],[2],[3],[4],[5],[6],[7] Recent changes in RC therapy, such as watch and wait, carry a higher risk of local recurrence, although local recurrence may occur after TME surgery, local excision, or watch and wait.

Clinical symptoms of local recurrence may be similar to the initial presentation with bleeding, change in bowel habits, or pelvic pain. At times, the recurrence may be asymptomatic and noted on surveillance imaging or with an elevated CEA. Inadequate surgery is considered a major risk factor for local recurrence, including incomplete total mesorectal excision and positive surgical margins.[6],[8],[9] Other risks are omission of chemoradiotherapy for locally advanced disease, T4 stage, N2 stage, obstruction, perforation, positive extra-mesorectal (pelvic side-wall) lymph nodes, surgeons who perform less than 20 rectal cancer resections per year[10],[11],[12],[13],[14],[15],[16],[17],[18], distal cancers, lack of treatment response, lymphovascular invasion, poorly differentiated tumors, and male gender.[19],[20],[21],[22],[23],[24],[25]

Upon discovery of local recurrence, work-up is similar to that performed for newly-diagnosed patients. Colonoscopy is recommended for biopsy and to look for metachonous tumors; if the tumor is extraluminal, endoscopic ultrasound-guided biopsy is an option.[26] If endoscopic biopsy is not available, computed tomography (CT)-guided biopsy is recommended before treatment. While tissue confirmation of recurrence is the goal, at times sampling can lead to false negatives. Clinical acumen must prevail. A rising CEA, increasing size on imaging, and positron emission topography (PET) positivity are suspicious for recurrent cancer even with negative biopsy.[27] MRI is essential for local recurrences, for the detailed assessment of resectability and for surgical planning.[27]

It is imperative to gather records on the initial presentation with available CT scans and MRI to review. Previous medical and radiation oncology records should also be reviewed, to assess which neoadjuvant or adjuvant therapies were delivered and responses to therapies. The operative report should be evaluated for clues on close margins or intraoperative difficulties. The post-operative pathology report should be carefully reviewed for margins, TME grade, and histological markers of risk of recurrence such as lymphovascular invasion, grade and number of positive lymph nodes.

In the clinic, the surgeon should assess for pain, neurological dysfunction, evidence of lower extremity swelling, assessment of sphincter function, and the relationship of the tumor to the sphincter, vagina, or prostate. Assessment of current performance status to be able to tolerate major surgery is required. Usually, the work-up and assessment allow time to help patients to attempt to optimize their nutritional status with a dietitian consult. If prostate or bladder involvement is present, a frank discussion of urostomy and loss of sexual function is required. For women with vaginal involvement, the importance to the patient of preserving vaginal sexual activity should be ascertained. Consultations with urology and/or gynecology and/or plastic surgery are arranged as indicated. In some centers, the primary team performs sacrectomies, but in some centers, neurosurgery or orthopedic surgery are consulted in such cases.

Once imaging is completed, all patients with local recurrence should be presented in a multidisciplinary tumor board conference. The principles in managing these patients include:

1. Thorough evaluation for distant metastatic disease should be performed, because pelvic exenteration is often not recommended if patients have distant metastases (although it is recommended in selected cases, depending on patient age, performance status, extent of metastatic disease, timeframe of recurrence, and symptoms).

2. Patients with local recurrence who have not previously had radiation therapy to the pelvis should almost always have radiation prior to surgery.

3. The goal of treatment is R0 resection, with resection of adjacent organs and structures as required. Intraoperative radiation therapy (IORT) may be a useful adjunct to surgery. Consider referring patients requiring difficult resections or IORT to specialty centers that perform frequent exenteration procedures and have the multidisciplinary surgical teams required.

R0 resection is the best predictor of survival after resection for local recurrence. The position of recurrence is the key predictor of resectability. Tumors that are anastomotic, or involving urogynecological structures are more often amenable to R0 resection than those involving para-aortic tissue, sacrum or lateral pelvic sidewall.[28]

If an R0 surgical resection is not possible, patients are typically treated with chemotherapy and/or radiation therapy, and in some cases unresectable cases can be reassessed for resection after therapy. If the patient is radiation naȇve, neoadjuvant radiation therapy is usually recommended. Even with previous radiation, depending on the previous fields and current position of recurrence, at times a smaller dose can be entertained. This is where the input of the multidisciplinary team is imperative.[26],[29]

For surgery, the patient is usually placed in lithotomy position. Especially for the lower rectal recurrences this allows combined abdominal and transperineal approaches that may be followed by reconstruction of the perineum. Also, in women with vaginal involvement this allows a two-team combined transabdominal and transvaginal approach. Ureteral stents are usually indicated in re-do pelvic surgery. Initial exploration for metastatic disease is necessary and any lesions of concern are to be biopsied and sent for a frozen section. If positive, palliative resection is considered while minimizing operative morbidity.

The goal of surgery is to resect the tumor en bloc with adherent structures and organs. The final specimen should be well oriented and in many institutions the surgeon can carry the specimen directly to the pathologists to aid in orientation and point out areas of concerns of close margins. Marking sutures should be placed for identification of areas of concern for close margins. These areas should be assessed by frozen section. If positive, and further resection is possible, this should be performed and once again frozen section should be performed to confirm the R0 dissection. If wider margins are not possible then IORT should be considered if available.

For recurrent low rectal cancers frequently the sphincter complex is involved and an abdominal perineal resection is performed. Nearly all of these patients have received previous radiation, and the risk of a nonhealing wound is 7-66%. Plastic surgery myocutaneous flaps are the best strategy for minimizing the risk of large non-healing wounds. These can also be used to reconstruct the vagina in women who desire to retain vaginal sexual activity, although function of the neovagina varies and some women are not able to resume vaginal intercourse.[28],[30]

Patients who undergo therapy for locally-recurrent rectal cancer have up to 53% distant recurrence at 5 years, and therefore adjuvant chemotherapy is usually recommended.[29] While optimal regimen or length can be debated, knowing the previous chemotherapies that have been utilized and the response to these chemotherapies, along with microsatellite and KRAS status will help guide the medical oncologist on the multidisciplinary team.

Patients with locally recurrent rectal cancer and their physicians must balance the potential benefits of an R0 resection with the patient’s health and ability to tolerate such radical surgery, as well as their willingness to accept the short- and long-term morbidity of treatment. Therefore, contraindications to surgery will vary amongst institutions, surgeons, and patients. For healthy, motivated patients who will require very difficult resections, consider referral to tertiary and quaternary centers where such radical surgery can be accomplished with meaningful success rates. While each recurrent rectal cancer study is a heterogeneous group of patients with variable selection processes, 5-year survival can be up to 40%.[29] In specialty centers, good results have been reported even with pelvic sidewall tumors, sacral resections above S3, and aortoiliac axis reconstruction.[1],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41]

Attaining R0 status is the goal for long term survival. The 5-year survival for R0 resections is approximately 40% while R1/R2 is 16% and in one study no patient with R2 resections lived past 3 years.[18] [28] [32] [37] [28][42][43]

Palliation is another goal, particularly for those with symptomatic local recurrences and metastatic disease.[43] Patients may be candidates for external beam radiation to palliate bleeding, obstruction, and pain.[26] Diverting colostomy may be effective in palliative management of pain, defecatory dysfunction, and/or obstruction. Chemotherapy can prolong survival and decrease symptoms for some patients. A team approach with palliative medicine input is imperative to discuss the pathway the patient and family desire to take with discussion of goals. This is a journey with direction which may change several times and therefore early discussion helps patients and the palliative team to build relationships so there is comfort on these decisions, which may ultimately lead to hospice care. Palliative care has been shown to improve outcome without shortening survival.[44]

In summary, locally-recurrent rectal cancer is one of the most challenging of all colorectal diseases. Recurrence is often due to inadequate primary resection, though tumor biology also plays a role. Decision-making requires a multidisciplinary team approach, and also the input of the patient care goals along their journey. Cure usually requires major surgical intervention, and R0 resection is the goal.

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Last updated: September 20, 2021