How to Treat Metastatic Colorectal Cancer

Bassel El-Rayes, MD, Professor and Vice Chair for Clinical Research, Department of Hematology and Medical Oncology, Associate Director for Clinical Research, and Director of the Gastrointestinal Oncology Program Winship Cancer Institute of Emory University

Q: You have just received a new patient, referred to you from Macon, GA. She is a 52-year-old white woman in good general health who is 3 months post op from a left hemicolectomy for a grade 3 adenocarcinoma with extension through muscle but not through the serosa. Three of 15 lymph nodes were positive for cancer. She did not receive post-op radiation or chemotherapy. No molecular testing of the tumor was performed. She now presents with a single 3 cm mass in the liver discovered by CT scan. How will you manage her care?

A: (2016) This 52-year-old patient presents with a solitary liver lesion 3 months after resection of a stage III colon primary. If all her other staging is negative, my first question is do we proceed directly to surgery or should we try chemotherapy first? The short interval between the original cancer and the recurrence makes the case for using chemotherapy upfront followed by surgery. FOLFOX would be the chemotherapy of choice. The biologic agent may be influenced by the molecular profile of the tumor specifically RAS mutational status and MSI. Furthermore, knowing the BRAF mutational status may provide valuable information regarding prognosis. For these reasons, I would obtain a genomic profiling of the tumor. I would administer 2 to 3 months of chemotherapy and then obtain re-staging scans. My overall objective would be to complete roughly 6 months of therapy and follow that by surgical resection or ablation of the liver lesion.
A: (2017) The starting point for the management of this patient is to decide whether to do surgical resection only or to use surgery plus systemic therapy. Given she had initially stage III disease and did not receive adjuvant therapy and the short time interval between resection and recurrence, my preference would be to consider systemic therapy. The second question is about the sequencing of therapies. My preference is to do the chemotherapy first since this will allow for evaluation of responsiveness to therapy. The third question: what type of systemic therapy? This decision is driven by the clinical presentation (left versus right side), molecular profile specifically MSI, extended RAS and BRAF, as well as overall health of the patient. For the right-sided tumors, there is now sufficient data to recommend using bevacizumab in combination with chemotherapy as front-line agent. In the left-sided tumors, there are more options for the biologic agent including bevacizumab or an EGFR inhibitor in the extended RAS wild type. In the mutated RAS, the main option is still bevacizumab. In the MSI-high tumors, consideration of PD-1 antibody without chemotherapy is warranted although data for use of a checkpoint inhibitor in the frontline setting is still limited. The last question is related to the duration of therapy. With the recently presented data in the adjuvant setting showing the relatively small benefit for 6 months over 3 months, I would lean towards giving only 3 months of therapy in this case prior to proceeding to surgery.
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