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Stage IV and Recurrent Rectal Cancer

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Patients with hepatic metastases that are deemed unresectable will occasionally become candidates for resection if they have a good response to chemotherapy. These patients have 5-year survival rates similar to patients who initially had resectable disease.[33] Radiofrequency ablation has emerged as a safe technique (2% major morbidity and <1% mortality rate) that may provide long-term tumor control.[69,70,71,72,73,74,75] Radiofrequency ablation and cryosurgical ablation remain options for patients with tumors that cannot be resected and for patients who are not candidates for liver resection.[76,77,78]

Other local ablative techniques that have been used to manage liver metastases include embolization and interstitial radiation therapy.[79,80,81] Patients with limited pulmonary metastasis, and patients with both pulmonary and hepatic metastasis, may also be considered for surgical resection, with 5-year survival possible in highly selected patients.[82,83,84,85]

The role of adjuvant chemotherapy after potentially curative resection of liver metastases is uncertain. A trial of hepatic arterial floxuridine and dexamethasone plus systemic 5-FU/LV compared with systemic 5-FU/LV alone showed improved 2-year PFS (57% vs. 42%, P =.07) and OS (86% vs. 72%, P = .03) for patients in the combined therapy arm but did not show a significant statistical difference in median survival, compared with systemic 5-FU therapy alone. Median survival in the combined therapy arm was 72.2 months versus 59.3 months in the monotherapy arm (P = .21).[86][Level of evidence: 1iiA]

A second trial preoperatively randomly assigned patients with one to three potentially resectable colorectal hepatic metastases to either no further therapy or postoperative hepatic arterial floxuridine plus systemic 5-FU.[87] Among those randomly assigned patients, 27% were deemed ineligible at the time of surgery, leaving only 75 patients evaluable for recurrence and survival. Although liver recurrence was decreased, median or 4-year survival was not significantly different between the patient groups. Additional studies are required to evaluate this treatment approach and to determine whether more effective systemic combination chemotherapy alone would provide similar results compared to hepatic intra-arterial therapy plus systemic treatment.

Hepatic intra-arterial chemotherapy with floxuridine for liver metastasis has produced higher overall response rates but no consistent improvement in survival when compared with systemic chemotherapy.[16,88,89,90,91,92] Controversy regarding the efficacy of regional chemotherapy was the basis of a large multicenter phase III trial (CALGB-9481) (NCT00002716) of hepatic arterial infusion versus systemic chemotherapy. The use of combination intra-arterial chemotherapy with hepatic radiation therapy, especially employing focal radiation of metastatic lesions, is under evaluation.[93] Several studies show increased local toxic effects with hepatic infusional therapy, including liver function abnormalities and fatal biliary sclerosis.

Locally Recurrent Rectal Cancer

Locally recurrent rectal cancer may be resectable, particularly if an inadequate prior operation was performed. For patients with local recurrence alone following an initial, attempted curative resection, aggressive local therapy with repeat LAR and coloanal anastomosis, APR, or posterior or total pelvic exenteration can lead to long-term disease-free survival.[94,95] 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.[96,97] Intraoperative radiation therapy in patients who received previous external-beam radiation may improve local control in patients with locally recurrent disease, with acceptable morbidity.[3]

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