Impact of Microsatellite Stability in Metastatic Colorectal Cancer


Dr Marshall describes the impacts of microsatellite stability and instability on metastatic colorectal cancer.

John L. Marshall, MD: Every patient with colon cancer and every physician treating colon cancer needs to know the microsatellite status of all patients. This should be tested in every patient with colon cancer from diagnosis, regardless of stage. It should be part of the initial pathology report. It doesn’t change much, if at all, over time, so you probably don’t need to repeat it. Most patients are microsatellite stable, and a few are microsatellite instable [MSI]. It can be tested by immunohistochemistry, next-generation sequencing, and fragment analyses. [Those] are the 3 main ways to do it. Most are getting immunohistochemistry. If [they’re] microsatellite instable, then do genetic analysis to confirm and make sure you do germline testing to see if the patient is has Lynch syndrome. [It’s] required testing for every patient with metastatic colon [cancer], regardless of stage.

If your patient is MSI high, immunotherapies will work and play an important role in those patients. Even in patients with earlier-stage rectal cancers, for example, we want to know because we might be able to avoid surgery by treating that patient with immunotherapy as the sole treatment. In metastatic disease, frontline immunotherapy is a standard instead of chemotherapy. This is a predictor for responsiveness to immunotherapy, but it’s also important to remember that comes often with a germline mutation for Lynch syndrome, hereditary nonpolyposis colon cancer. If you’re MSI high, then the patient also needs to know if they have a germline test that’s positive. Those are 2 different things—somatic on the tumor and germline on the patient—so you need to know it for prognostic and predictive reasons.

Transcript edited for clarity.

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