How an Expert Would Manage Her Own Advanced Colorectal Cancer: An Update

When facing a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Here, our Curious Dr. George asks oncologist Christina Wu, MD, how she would handle her own diagnosis of metastatic colorectal cancer. Dr. Wu is a Professor of Medicine at the Mayo Clinic in Phoenix, Arizona. (Note: This piece originally appeared in 2020; now, Dr. Wu provides her updated expert perspective on molecular testing, targeted therapies, surgery, and clinical trials.)

Curious Dr. George: As an experienced academic and practicing clinical oncologist at the Mayo Clinic, you have particular interest, training, and experience in colorectal cancer. What would you do if you personally were discovered to have an asymptomatic, unsuspected, non-obstructing adenocarcinoma of the ascending colon that had already metastasized to your liver?

Christina Wu, MD: Colorectal cancer is one of the most common cancers in the U.S., and there has been a noticeable rise in early-onset colorectal cancer. Every patient with metastatic colon cancer to the liver is uniquely assessed because there are systemic and liver-directed treatment options. If I were diagnosed with colon cancer and liver metastasis, I would want a multi-pronged approach to include the following:

Next-generation sequencing (NGS): First of all, I would want both blood and tumor NGS testing. Blood NGS results can be back within a week, and tumor NGS is more expansive and complete. The tumor biomarkers I would want to know first are mismatch repair (MMR) protein or microsatellite instability (MSI) status. If deficient MMR or MSI-high, I could benefit from immunotherapy (pembrolizumab or nivolumab with or without ipilumumab) and be spared chemotherapy. Other tumor markers include KRAS/NRAS/BRAF mutation (mt), HER2 amplification, and NTRK and RET gene fusion.

I would be eligible for anti-EGFR antibody (panitumumab or cetuximab) in combination with doublet chemotherapy (FOLFOX or FOLFIRI) if my tumors were KRAS/NRAS/BRAF wild-type (wt) and HER2-negative with a left-sided primary cancer. HER2-targeted therapy such as tucatinib and trastuzumab could be a chemotherapy-free option if the tumor was KRAS/NRAS/BRAF wt and HER2 positive. Trastuzumab-deruxtecan could also be offered if I was HER2 positive. A BRAF V600E mt would be targeted with encorafenib and an anti-EGFR antibody. A KRAS G12C mt would be targeted with sotorasib/adagrasib and cetuximab/panitumumab. If I had the rare NTRK fusion mutation, I could be treated with entrectinib, larotrectinib, or repotrectinib. RET gene fusion could be targeted with selpercatinib.

Multi-disciplinary tumor board: I would want high-quality imaging and experts from medical oncology, surgical oncology, colorectal surgery, radiation oncology, gastroenterology, radiology, and interventional radiology reviewing my case in a tumor board. It would be meaningful to know upfront whether the liver metastasis was surgically resectable, because I may opt to receive systemic chemotherapy followed by surgical resection. If I required conversion therapy or reduction in my tumor burden, I would consider triplet chemotherapy (FOLFOXIRI) or systemic targeted therapy to get more of a response so that I could get to surgery. However, if I had clearly unresectable disease, I would choose systemic targeted therapy or doublet chemotherapy, such as FOLFOX or FOLFIRI and bevacizumab, to improve my quality of life.

With unresectable disease, I could also consider radiation, Y90 treatment, or ablation to the liver tumors, if I had good control or surgical resection of the extrahepatic disease. In addition, liver transplant may be a future consideration if I had well-controlled, unresectable liver metastasis, with no evidence of extrahepatic metastasis. Although not present at a tumor board, the palliative care team would be a crucial component of my care.

Genetic counseling: Some hereditary syndromes lead to colon cancer development, including Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis. I would choose to pursue germline testing to screen for such conditions.

Clinical trials: There are studies looking at targeting KRAS mutations, bringing targeted therapy to the first-line setting, and providing immunotherapy combinations. I would definitely want to expand my therapy options by enrolling in clinical studies.

Final thoughts: Systemic and liver-directed treatment options are evolving, and thus a multi-disciplinary approach would be essential from the moment of my diagnosis.

Dr. Wu can be reached at wu.christina@mayo.edu.

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