(1) Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. Up to 50% of patients with CRC develop metastatic CRC (mCRC). Surgical and systemic therapy advances can now offer significant survival advantages. Understanding the evolving treatment options is essential for decreasing mCRC mortality. We aim to summarize current evidence and guidelines regarding the management of mCRC to provide utility when making a treatment plan for the heterogenous spectrum of mCRC. (2) Methods: A comprehensive literature search of PubMed and current guidelines written by major cancer and surgical societies were reviewed. The references of the included studies were screened to identify additional studies that were incorporated as appropriate. (3) Results: The standard of care for mCRC primarily consists of surgical resection and systemic therapy. Complete resection of liver, lung, and peritoneal metastases is associated with better disease control and survival. Systemic therapy now includes chemotherapy, targeted therapy, and immunotherapy options that can be tailored by molecular profiling. Differences between colon and rectal metastasis management exist between major guidelines. (4) Conclusions: With the advances in surgical and systemic therapy, as well as a better understanding of tumor biology and the importance of molecular profiling, more patients can anticipate prolonged survival. We provide a summary of available evidence for the management of mCRC, highlighting the similarities and presenting the difference in available literature. Ultimately, a multidisciplinary evaluation of patients with mCRC is crucial to selecting the appropriate pathway.
Keywords: metastatic colorectal cancer; stage IV colon cancer; stage IV rectal cancer; treatment of stage IV colorectal cancer.