Colorectal cancer is currently the fourth most common malignancy in the United States.1 The liver is the most common site of metastatic disease, with around 30% of patients developing colorectal liver metastases (CRLM) at some point in their course of disease.2 More than 80% of patients, however, will have unresectable disease. With chemotherapy alone, the median overall survival in this cohort is 20 to 22 months, with a 5-year overall survival less than 15%.3,4 In those 10 to 20% of patients with resectable CRLM who undergo complete resection, 5-year overall survival is significantly improved at 31 to 58%.5,6 However, 75% of these patients will develop disease recurrence within a two-year period.

Major liver resection is associated with significant postoperative morbidity and mortality. As such, over the last several decades there has been a shift towards more minimally invasive and parenchymal sparing techniques. Current treatment algorithms for the management of resectable CRLM favor modern chemotherapy regimens accompanied by less invasive procedures such as minor liver resections, liver ablation and embolization. Not only have these procedures pushed the boundaries of the definition of resectable disease, but patients are able to undergo repeated treatments for disease recurrence enabling prolonged survival. In this chapter we review various liver directed therapy options for CRLM and discuss the utility and timing of systemic chemotherapy in the treatment algorithm.