Colorectal cancer is the third most commonly diagnosed cancer in the United States. Approximately 20% of patients have metastatic disease at diagnosis, and a proportion of patients with initially localized disease will experience systemic disease recurrence. In the era of molecular subtyping, we have an increasing number of systemic therapies and the opportunity to individualize the treatment of patients with advanced disease. Nonetheless, the 5-year overall survival rate remains unsatisfactory for this patient population. Most patients will be treated with palliative cytotoxic therapy, often with an added monoclonal antibody. Molecular subtyping allows patients to receive targeted therapies upon further lines of therapy. A small portion of patients will have oligometastases that may be amenable to resection or locoregional therapies to help improve outcomes with systemic therapy. Here, we review the current treatment of patients with unresectable and resectable stage IV colorectal cancer, with a focus on pharmacologic therapies.
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