Transcript: John L. Marshall, MD: Let me get everybody’s opinion. Today, a year or 2 before we have data from more studies, how do we manage a midrectal T3 who, by imaging, is N1, 8 cm up, and otherwise fit? Do we use traditional chemoradiation or chemoradiation and surgery? Chris?

Christopher Lieu, MD: At our institution, we would do total neoadjuvant therapy, probably on the NRG-GI002 study, the TNT trial, but even off study.

John L. Marshall, MD: But even off the study.

Christopher Lieu, MD: Even off the study, we would offer total neoadjuvant therapy.

John L. Marshall, MD: And it would be what you walk in the room telling them.

Christopher Lieu, MD: Exactly.

John L. Marshall, MD: OK. Joleen?

Joleen M. Hubbard, MD: So is only 1 lymph node positive?

John L. Marshall, MD: One lymph node. One enlarged lymph node.

Joleen M. Hubbard, MD: You’re making it hard. Outside a study, I think there are enough data to suggest that that’s a good approach. You don’t have to do it that way. You don’t have to do TNT, but I would be comfortable doing that given the data we have thus far.

John L. Marshall, MD: Howard?

Howard S. Hochster, MD, FACP: I tell the patient to do the chemoradiation and surgery and then the chemotherapy at the end, but I also would probably encourage them to get the chemotherapy up front. I think the response rates are so good that you don’t really lose anything, and you may get the additional benefit of treating the metastatic cells, which is what we’re giving the systemic therapy for, treating them earlier.

John L. Marshall, MD: Yeah, and to Joleen’s point about the shorter interval with the ostomy.

Tanios S. Bekaii-Saab, MD: I’m going to make a pitch for total neoadjuvant therapy as a standard. I’ll give you an example. I don’t believe that it necessarily offers a significant advantage. I think you offer more patients the opportunity to be on it. But I think we still see those patients who actually end up having surgery first, before a discussion, and come to us. I think we need to shift the balance for our surgeons in the community and even in some academic practices to force them into that discussion. Because most of these patients do need treatment before surgery. And I want to move the whole discussion from “you can’t get it after.” You have to give everything before. What you do with it ultimately will be a discussion with the patient. But I think the oncologist has to get into the discussion, and the radiation oncologist, and the others, from day 1. There needs to be a multidisciplinary team approach. I don’t want to see another patient with rectal cancer who had surgery first, and I don’t know what to do after that.

John L. Marshall, MD: But our obligation as academicians and the people who are running these trials is to get the data in the hands of the people who need it so that they can make decisions.

Howard S. Hochster, MD, FACP: I think the real question, Tony, is for the patient, who has an MRI [magnetic resonance imaging] or transrectal ultrasound that looks like T2, N0 and then they have more after surgery. Those are the ones that we usually get stuck with.

Tanios S. Bekaii-Saab, MD: I totally understand. But the problem is, you can have that discussion. Oftentimes, you see patients who never had a discussion except with a surgeon, and they’ve had the surgery happen. I think there are enough data across the world of oncology that suggest that total neoadjuvant approaches are actually the right way to go. It’s the best way probably to get more patients exposed to lifesaving chemotherapy plus or minus radiation in addition to surgery.

John L. Marshall, MD: You guys are amazingly brilliant. This has really, hopefully, been informative for you guys out there. Before we end, I’d like to get some closing thoughts from each of our panelists. Howard, you get the first word.

Howard S. Hochster, MD, FACP: Well, I think it’s an exciting time as we begin to understand some of the molecular subsets. I’m really looking forward to the era when we’re going to be using circulating tumor DNA to decide on our adjuvant treatments and even our metastatic treatments. I mean, we know like for EGFR therapies, people can get transient RAS-mutation clones coming up. I think understanding all this better and getting to look at the circulating tumor DNA to help us guide our therapy is going to be really important in the next decade.

John L. Marshall, MD: Cool. Joleen?

Joleen M. Hubbard, MD: Yeah. I think we are at an exciting time with next-generation sequencing, not just to identify our known positive and negative predictive markers for colorectal cancer, but also people should keep in mind the clinical trial opportunities. If we get a FoundationOne test that identifies a novel mutation that we have a clinical trial for, that may be the next larotrectinib. So I think it’s so important, as Tony already mentioned, that everybody should have next-generation sequencing.

John L. Marshall, MD: Great. Chris?

Christopher Lieu, MD: Be on the lookout for ctDNA studies coming. There will be a stage II trial open in our country, and there will be a stage III trial looking at ctDNA in the future. When you look at what we’ve talked about on this panel today, test your patients with next-generation sequencing. Test them early, so that you know what your patients would be eligible for. There are so many biomarker-directed clinical trials for metastatic colorectal cancer. There’s a trial for MSI [microsatellite unstable], there’s a trial for HER2, there’s a trial for BRAF. Get that testing, and get it early. Know what clinical trial options are available to your patients and help us enroll.

John L. Marshall, MD: Great. Tony, you have the last word.

Tanios S. Bekaii-Saab, MD: I don’t know how much I can add to these wonderful statements. Just to summarize, this is an exciting time in colorectal cancer. I think the strides that we’re seeing, the improvement in survival—we are talking about 3, 4, 5 years median survival, even in the most metastatic setting—it’s just a testament to how far we’ve come. I agree with everyone that we have to be more aggressive, have to think about genomic markers [and] immune markers and integrate them into day-to-day decision making.

John L. Marshall, MD: Good. Thank you. My fingers are crossed on RAS-targeted agents starting to make it to the clinic. This could be the year. So thank you all for your contributions to our discussion, and, on behalf of the whole panel, we really thank you for joining us. We hope that you found this OncLive Peer Exchange® to be useful and informative.

Transcript Edited for Clarity