Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Locally recurrent rectal cancer may be resectable, particularly if an inadequate prior operation was performed. For patients with local recurrence alone following initial attempted curative resection, aggressive local therapy with repeat low anterior resection and coloanal anastomosis, abdominoperineal resection, or posterior or total pelvic exenteration can lead to long-term disease-free survival.[1] The use of induction chemoradiation for previously nonirradiated patients with locally advanced (pelvic side-wall, sacral, and/or adjacent organ involvement) pelvic recurrence may increase resectability and allow for sphincter preservation.[2,3] Intraoperative radiation therapy in patients who received previous external beam radiation may improve local control in patients with locally recurrent disease with acceptable morbidity.[4] The presence of hydronephrosis associated with recurrence appears to be a contraindication to surgery with curative intent.[5] Patients with limited pulmonary metastases and patients with both pulmonary and hepatic metastases, may also be considered for surgical resection, with 5-year survival possible in highly selected patients.[6,7,8]

In stage IV and recurrent rectal cancer, chemotherapy has been used for palliation with fluorouracil (5-FU)-based treatment and is considered to be standard therapy.[9,10] 5-FU has been shown to be more cytotoxic, with increased response rates but with variable effects on survival, when modulated by leucovorin,[11,12,13,14,15,16,17] methotrexate,[18] or other agents.[19,20,21,22,23] Interferon alfa appears to add toxic effects but no clinical benefit to 5-FU therapy.[24,25] Continuous-infusion 5-FU regimens have also resulted in increased response rates in some studies, with a modest benefit in median survival.[26] The benefits of continuous-infusion 5-FU compared to bolus regimens have been summarized in a meta-analysis.[27] Oral regimens using prodrugs of 5-FU or inhibitors of DPD pharmacologically simulate continuous infusion and are under clinical evaluation.[28] The choice of a 5-FU-based chemotherapy regimen for an individual patient should be based on known response rates and toxic effects profile of the chosen regimen, as well as cost and quality-of-life issues.[29,30] Innovative ways of altering toxic effects patterns, and potentially improving clinical benefit, include chronomodulated therapy, in which drug doses are varied throughout the day to allow for greater dose intensity without increased toxic effects.[31,32] In a meta-analysis of 1219 patients in randomized trials where patients were assigned to receive 5-FU with or without leucovorin via either continuous infusion or bolus, neutropenia was noted in 4% of patients who received continuous infusion versus 31% of patients who received bolus and hand-foot syndrome was found in 34% of patients who received continuous infusion versus 13% of patients who received bolus. All other toxic effects were noted with similar frequency and severity, regardless of continuous infusion or bolus administration.[33]