Abstract
Colorectal cancer (CRC) management continues to evolve. In metastatic CRC, several clinical and molecular biomarkers are now recommended to guide treatment decisions. Primary tumor location (right versus left) has been shown to predict benefit from anti-epidermal growth factor receptors (EGFRs) in rat sarcoma viral oncogene homologue (RAS) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) wild-type patients. Anti-EGFR therapy has not resulted in any benefit in RAS-mutated tumors, irrespective of the primary tumor location. BRAF-V600E mutations have been associated with poor prognosis and treatment resistance but may benefit from a combination of anti-EGFR therapy and BRAF inhibitors. Human epidermal growth factor receptor 2 (HER-2) amplification was recently shown to predict relative resistance to anti-EGFR therapy but a response to dual HER-2 targeting within the RAS wild-type population. Finally, the mismatch repair (MMR)-deficient subgroup benefits significantly from immunotherapeutic strategies. In addition to the increasingly complex biomarker landscape in CRC, metastatic CRC remains one of the few malignancies that benefits from metastasectomies, ablative therapies, and regional hepatic treatments. This treatment complexity requires a multi-disciplinary approach to treatment and close collaborations between various stakeholders in large cancer center networks. Here, we describe the City of Hope experience and strategy to enhance colorectal cancer care across its network.
Highlights
Colorectal cancer is the second most common cause of cancer-related death in the United States, with an annual incidence of 145,000 cases in 2019 and 51,000 deaths according to the American Cancer Society [1]
The management of metastatic colorectal cancer must take into consideration sidedness, as well as molecular biomarkers including rat sarcoma viral oncogene homologue (RAS), BRAF, Human epidermal growth factor receptor 2 (HER-2), and mismatch repair (MMR) status
We have previously extensively reviewed this topic [5,6]. It is well-established that the benefits of anti-epidermal growth factor receptors (EGFRs) therapy appear to be limited to RAS and BRAF wild-type tumors that originate from the left colon [7,8,9]
Summary
Colorectal cancer is the second most common cause of cancer-related death in the United States, with an annual incidence of 145,000 cases in 2019 and 51,000 deaths according to the American Cancer Society [1]. The life-time risk of developing colorectal cancer in men and women is 4.6% and 4.2%, respectively, according to 2014–2016 data [2]. The five-year survival rate for metastatic disease and regional disease are 14.2% and 71.3%, respectively [3,4]. Significant progress is still needed, especially in metastatic colorectal cancer settings. We will review the latest approaches in the treatment of metastatic disease. We will explore the City of Hope approach to delivering optimized care with partnership between academic researchers and community clinicians in cancer care
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