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It has been clear for many years that resection of liver metastases in patients with colon cancer can result in long-term survival. Prior to the advent of effective chemotherapy, 5-year survival rates after resection of colorectal metastases were in the range of 25%. Fong, in 1999, identified five independent predictors of poor outcome after resection- node (+) primary, diseases-free interval < 12 months, number of tumors > 1, size of largest tumor > 5cm, and CEA level > 200 ng- and developed a scoring system to estimate the likelihood of recurrence that has been widely used. As chemotherapy evolved beyond 5-fluorouracil and leukovorin to include first irinotecan and then oxaliplatin, measurable responses to treatment became common; with the addition of targeted agents such as bevacizumab and, in K-RAS wild-type tumors cetuximab, results have further improved. In 1996 Bismuth first reported resection of initially unresectable liver metastases after downstaging with oxaliplatin-based chemotherapy in 53/330 patients (16%) with 40% 5-year survival, comparable to that achieved in their patients with initially resectable disease. Chemotherapy can have negative impact on the liver, though; irinotecan is associated with steatohepatitis and oxaliplatin with venoocclusive disease, both of which, when severe, can limit respectability and worsen results. Another concern has been the disappearance of lesions with chemotherapy; Benoist in 2006 showed that among 66 metastases that disappeared during chemotherapy, residual disease ultimately proved to be present in 55 (83%). Nordlinger in 2008 published that in a multicenter trial comparing perioperative chemotherapy (6 cycles before and 6 cycles after surgery) to surgery alone for initially resectable metastases there was an insignificant trend towards improved progression-free survival but there was also an increase in perioperative complications. Technical advances in liver surgery including portal vein embolization and staged resections have expanded the definition of resectability, and in patients with synchronous presentation of primary colorectal cancer and liver metastases initial chemotherapy rather than the traditional resection of the primary tumor followed by chemotherapy has become the standard (unless complications such as bleeding or obstruction force the issue), enabling many patients to undergo combined resection of the primary and metastatic tumors. Many questions remain open, but there has been tremendous progress; through a multimodality approach, increasing numbers of patients are eligible for surgery, and five year survival in many centers now exceeds 50%. |
