Postsurgical ctDNA Surveillance in Locally Advanced CRC
Insights From: Axel Grothey, MD, West Cancer Center, University of Tennessee; John Marshall, MD, Ruesch Center for the Cure of Gastrointestinal Cancers
Axel Grothey, MD: At this point, when we follow patients after surgery we use imaging scans and we use CEA [carcinoembryonic antigen] levels to identify patients who are at risk of recurrence. We follow them over time, even after adjuvant therapy, to identify potentially resectable metastatic disease in an early stage. Now, we do know that it takes time for a tumor to grow before we actually see the tumor on scans, and CEA is not a great marker because it’s negative in a lot of patients. It’s not very sensitive, etcetera. So having a longitudinally available test that has high sensitivity and high specificity, like ctDNA [circulating tumor DNA], with the data that we see right now opens the door for very different surveillance patterns. We might only do scans when we see that a ctDNA test turns positive so we can spare patient scans over time.
The other point is, of course, treatment decisions. We might not need to give chemotherapy to a patient with a ctDNA-negative situation after surgery; and to longitudinally follow this patient only to really administer treatment when the test turns positive. On the other hand, we can also tell patients, based on the data that we’ve seen, if we have let’s say repeated tests for 2 years and they are all negative, the risk of recurrence is less than 3%, so 97% of patients who likely are free of disease at 2 years, which gives more reassurance for patients and clearly can help us really identify patients who need adjuvant therapy over time.
John Marshall, MD: Sensitivity and specificity of these kinds of tests is the most important question to ask. Sensitivity, remember, says, “I’ll pick up cancer DNA on a high frequency. I won’t miss too many.”
Here, the sensitivity is actually pretty good, particularly when it’s tumor-informed and particularly when you repeat it over time. One test has a pretty decent return. Doing another one, say a month later, even improves your return. So picking it up is very important.
Specificity means if it’s positive, it’s real, so we’re good there. But negative tests are what make us nervous. Positive: It’s there, it’s true. Negatives: We’re not 100% sure. We really need to optimize this, and there are studies going on looking at how to improve that. And that’s where more knowledge, more experience of how best to incorporate this will, I think, improve the sensitivity and specificity.