Investigating the Role of ctDNA in Colorectal Cancer: Next Steps

Blase Polite, MD: In terms of other abstracts presented at ASCO GI [American Society of Clinical Oncology Gastrointestinal Cancers Symposium], we have many variations on the themes I’ve discussed. There are other prospective cohort studies looking at ctDNA [circulating tumor DNA] and trying to refine the process. There’s a study using the Guardant Reveal assay, which is nontumor informed. It’s essentially an off-the-shelf test using a defined set of DNA markers as well as methylation status, trying to answer some of the questions that Natera has been looking at in the multitude of their studies. The advantage of something like Guardant Reveal is that it technically doesn’t require any tissue. There are situations where the tissue is hard to obtain, or the patient received neoadjuvant therapy for rectal cancer and the tissue has been obliterated; that assay may prove important.

There’s a lot of interest in looking at the dynamics of ctDNA change. Does it matter whether ctDNA at 2 time points stays stable or if it doubles or triples? For the clinicians out there, this is thinking about PSA [prostate-specific antigen] velocity, a concept many are familiar with. The idea is to look at quantitative change in ctDNA. There are preliminary data suggesting that quantitative change in ctDNA is prognostic of relapse. How can be used? Let’s say a stage IV NED [no evidence of disease] patient has positive ctDNA, and you and the patient aren’t excited about chemotherapy. You check another ctDNA 3 months later, and it’s doubled or tripled. Then you can confidently say that this cancer will return quickly. Whether my therapy will prove beneficial there, this must be studied. Similarly, patients with ctDNA who remain positive but stable are a population that you can watch more closely over time with serial imaging, and you don’t need to act until you find something.

There was another work looking at ctDNA published by our group at the University of Chicago looking at appendiceal cancer. We have a large volume of this peritoneal-only disease that displayed very good test characteristics for ctDNA positivity in patients with known peritoneal disease. This is 1 area that we weren’t sure how well we’d be able to pick up. It’s not as good as you would see with solid tumors in liver or colon cancers, but we’re finding that it’s useful in peritoneal disease. We’re beginning to see that the quantitative level of ctDNA helps us predict patients who have peritoneal-only disease vs patients who are at risk for visceral metastases. Those are all the areas: expanding it to some of these more unusual settings; looking at the nontumor-informed assays, which may have some advantages; and seeing whether the test characteristics hold up as well as those seen with Natera’s tumor-informed assay. Quantitative ctDNA is an important marker by itself and as a prognostic marker in these patients.

Transcript edited for clarity.