Transcript: John L. Marshall, MD: Everything we just said was really for stage III patients. So I keep struggling with, how does this translate into a stage II patient, high risk or regular risk, if you decided to treat? How does it translate into our rectal cancer patients, particularly as we’re doing a lot of neoadjuvant therapy? What do you think? Is it transitive math?

Joleen M. Hubbard, MD: It’s a good question.

John L. Marshall, MD: We’ll never do the studies, right? We’ll never do a 12,000-patient study in stage II disease.

Joleen M. Hubbard, MD: I think it’s important to look at the factors, such as the TNM stage. I think T4, across the studies, does confer a higher risk for recurrence. I think the N2 disease, higher lymph node burden, definitely is a risk. So I think regardless of whether you’re a stage III or stage II patient, if you have those high-risk features, more treatment is probably better.

Howard S. Hochster, MD, FACP: I think the game changer here is going to be circulating tumor DNA [ctDNA]. The fact of the matter is, for stage III, half the patients are already cured; and for stage II, it’s like two-thirds of the patients are already cured without any additional therapy. We just need to know how to identify those. I’m very optimistic that with the use of circulating tumor DNA, we’re going to be able to identify the higher-risk patients and not treat some of the people who are already cured.

John L. Marshall, MD: So I have a physician patient, as I’m sure many of us do, who has read this literature and gotten their test run—the circulating ctDNA test—and it was negative. They used that as reassuring component. Chris, would you order it on you? Would somebody down in the lab run this on your stage II blood?

Christopher Lieu, MD: I think the data are really striking.

John L. Marshall, MD: It is.

Christopher Lieu, MD: So the first study that was presented at ASCO [the American Society of Clinical Oncology Annual Meeting] showed a 0% relapse-free survival rate if you’re ctDNA-positive. And again, small numbers of patients. None of this data at this time are truly actionable. We need more clinical trial data. We need to look more at what the natural history of ctDNA is. Can we clear it? Can adjuvant therapy clear it? These are all questions that have to be answered to know whether this is truly and potentially a predictive marker. We certainly know it’s a prognostic marker, at this point. But can we really intervene on that in any way and make treatment decisions? I think that this is coming and this is extraordinarily exciting. This is going to be the next step that brings adjuvant therapy into a new era. But right now we’re at the very beginning of that.

John L. Marshall, MD: And if you think about how many people we give chemotherapy to who cannot benefit because they were already cured…

Tanios S. Bekaii-Saab, MD: Right, 80%.

John L. Marshall, MD: We talk about risk reduction and cost reduction and all those things. It would be huge.

Howard S. Hochster, MD, FACP: So there’s a lot of discussion in the NCTN [National Clinical Trials Network] group now about how to really do the right study. And with input from the patient advocacy community as well, it’s a very tough question. For your patient, I would say it’s not actionable today. I would probably do it myself, and if it was positive, I would be asking for FOLFOXIRI…

John L. Marshall, MD: And tracking it monthly, right?

Howard S. Hochster, MD, FACP: If it’s negative, I don’t know if that lets me off the hook. But if it’s positive, I’d be super worried.

Tanios S. Bekaii-Saab, MD: The other side of the coin is also those 20% of patients who don’t benefit from any of this.

John L. Marshall, MD: Right. So we need to be doing something different for them, right?

Tanios S. Bekaii-Saab, MD: Exactly. So we have to think about all the patients who, really, we could spare, in some way, surgery or chemotherapy, or improve upon how we treat their disease. Is it different?

John L. Marshall, MD: In the adjuvant setting it becomes so much more effective.

Tanios S. Bekaii-Saab, MD: Absolutely, and it’s heading that way, so that’s the good news.

Transcript Edited for Clarity