Colorectal cancer is the second most common cause of cancer-related death in the United States with liver metastases developing in 25-30% of patients.1 Approximately 15% of patients are found to have synchronous liver metastases at the time of diagnosis, among whom approximately 50% have isolated liver metastases.2 An additional 15-25% of patients are estimated to develop metachronous hepatic metastases within the first 5 years of their treatment.2,3 The prognosis for untreated colorectal hepatic metastases remains poor, with an estimated survival of 6-12 months. With modern surgical treatments, liver-directed therapies, and chemotherapeutic regimens, 5-year survival now ranges from 37-58%.3,4 Despite the improved prognosis, only 10% of patients with synchronous liver metastases undergo resection.5 For patients diagnosed with resectable colorectal hepatic metastases, variation exists regarding the timing of resection of the colorectal primary and the hepatic metastases.

In the “classical” colorectal-first approach, the primary tumor is surgically resected followed by resection of hepatic metastases in a staged fashion. However, this approach may delay or prevent the initiation of systemic chemotherapy for what is, by definition, systemic disease. It has also been hypothesized that the initial colorectal resection may serve to accelerate growth of hepatic metastases, possibly because of the immunosuppressive effect of surgery.6 Moreover, there has been controversy as to whether the staged approach results in greater cumulative morbidity or mortality in comparison to a simultaneous or “combined” approach to colorectal and hepatic resection for patients with synchronous colorectal liver metastasis. Even after definitive hepatic resection, there is a high risk of intra-and extra-hepatic disease recurrence with more than 50% of patients presenting with recurrent disease within 30 months of treatment.4 Patients with early recurrence may derive little oncologic benefit, with resultant worse quality of life, after resection of a colorectal primary. The “reverse” or liver-first staged approach may allow for shorter time to resection, mitigate physiologic insult if a major hepatic and high-risk colorectal resection are required, and allow for disease recurrence to declare before completing the staged surgical approach. With these competing interests, controversy remains regarding the optimal approach.

The purpose of this chapter is to review the current literature regarding the timing of colorectal and hepatic resection in patients with surgically treatable colorectal adenocarcinoma hepatic metastases. In doing so, we sought to propose a general framework for the multidisciplinary approach to caring for patients with oligometastic colorectal cancer to the liver.