Stacy A. Cohen, MD, and Mark Lewis, MD, discuss how DFS correlates with stage and adjuvant chemotherapy receipt in patients who are ctDNA-positive.
Mark Lewis, MD: I think this is probably the busiest slide to look at. It’s a little bit confusing to me in that now the stage 4 group has reentered, if you will. Although this is a slide that is looking at DFS [disease-free survival] by stage and receipt of adjuvant therapy, I can only presume and, you are right, we lack some of the granularity we might want. Here in the stage 4 group we’re maybe talking about pseudoadjuvant chemotherapy after oligo mastectomy. I just could not get that level of detail here. Again, what I take away from this is that ctDNA [circulating tumor DNA] positivity can be salvaged and that poor prognosis is not necessarily set by having a positive initial ctDNA signal. The one quibble I have here is if you look at that middle yellowish group–the stage 3 patients–the number of people who did not receive adjuvant chemotherapy I find puzzling because clearly it is standard of care to offer adjuvant chemotherapy to stage 3 patients and arguably to high-risk stage 2 as well. I think there are likely some confounding variables explaining why those patients weren’t receiving adjuvant chemotherapy. Dr [Rona] Yaeger [MD] gave her nuanced analysis of this abstract at ASCO 2022 GI [American Society of Clinical Oncology 2022 Gastrointestinal Cancers Symposium] after Dr [Masahito] Kotaka [MD, PhD] spoke and she pointed out this is a nonrandomized comparison with all the confounders there. Those are my lingering questions about this data, but, again, I think that the fact that the positive signal might be overcome by treatment selection is important and hopeful.
Stacey A. Cohen, MD: Right, the whole point of this is not to prognosticate and know that some patients are going to recur and which of those patients are. Of course we want that information, but what we really want is to be able to do something about it. I think this is just starting to hint at that predictive marker and how much influence we have. Do we really take the biomarker for what it is, or do we push up our sleeves and try to make it better? I think this is starting to hint at that, but it really comes back to me to the same initial problem of this is pathologic stage without any idea about what neoadjuvant therapy was received. Some of these are rectal cancer patients so they have short course or long course, or neoadjuvant chemotherapy TNT [total neoadjuvant therapy] style treatment, and all of those are going to influence it. You could imagine a high-risk stage 3 rectal cancer [patient] that got TNT and still had pathologic stage 3 disease. That patient is probably not going to do as well. As we look at that I think that is a confounding factor here as we think about the benefit of adjuvant therapy. Of course I looked at what they defined as high-risk stage 2, but notably absent was the presence of MSI [microsatellite instable] or MSS [microsatellite stable]. My assumption is that these are all microsatellite stable patients, but I do wonder if any of these individuals had microsatellite instability and would that influence outcomes both in terms of it being a better prognostic marker but [also] perhaps not benefitting from chemotherapy.
Mark Lewis, MD: It’s a classic problem with a trial of this scale. We’re getting more statistical weight and tighter confidence intervals, but we’re losing that patient level resolution and all these really important granular details that you bring up.
Stacey A. Cohen, MD: Exactly.
Mark Lewis, MD: Absolutely right.
Transcript edited for clarity.