Localized Colorectal Cancer — Microlearning Activity 1: Proceedings from a Session Held Adjunct to the 2026 ASCO GI Cancers Symposium

0:00Welcome to Experts Second Opinion, optimizing the use of immunotherapy, MRD assessment and other novel approaches for patients with localized colorectal cancer. This is medical oncologist Dr. Neo Love bringing you excerpts from a CME meeting we had at the recent 2026 gastrointestinal symposium meeting in San Francisco. This meeting was moderated by Dr. Chris Liu from the University of Colorado Cancer Center in Aurora, Colorado, with faculty members Dr. Stacy Cohn from the Fred Hutchinson Cancer Center University of Washington, Seattle, Washington, and Professor Jenny Seligman from the University of Leeds, Leeds United Kingdom. In the meeting, Dr. Seligman first did a presentation on Neoagement Treatment for Localized Colorectal Cancer, followed by a presentation from Dr. Liu on emerging novel

1:00approaches to Ag event treatment for localized colorectal cancer, and Dr. Cohn finished up with a talk on the role of circulating tumor DNA or CTDNA testing in localized colorectal cancer. For this program, we did a survey of 50 community-based general medical oncologists and SM to present cases and ask questions of the faculty and picked out the best ones to give to Dr. Liu to pose to his colleagues, beginning with a case from the survey. These are just real-life cases, and this is what we are all seeing in the community and at academic centers too, and so really highlights the fact that this data is present, but how do we really put this into practice? And so, we'll start with this. This really kind of comes down to asking a question, has the paradigm totally shifted away from chemo there before these patients? So, for this 54-year-old gem of rectal cancer, MSI-hide, the Fish and Mishra Matropair, has

2:01some comorbidities here. Oncology team is considering Neoagement PD-1 inhibitor instead of chemo-radiation. For these patients with locally advanced MSI-hide colorectal cancer, for you, Dr. Cohn, like at the University of Washington, have you completely done away with chemotherapy and chemo-radiation for these patients and move strictly to immune checkpoint inhibition? Tell us how you might approach this patient with rectal cancer. Thank you. I would say that we really have made some major changes to the paradigm, and really, I think, Jenny, as you pointed out, I mean, the outcomes are just tremendously better with immunotherapy when it works. And so, we have really shifted that all of these MSI-hide rectal cancer patients are getting Neoagement of immunotherapy. I think we also have to keep in mind that there is retrospective data that the MSI-hide patients might progress through standard TNT. So, I think it's not equivalent. I think it could be potentially harmful to go on, especially the new-adjuvant chemotherapy

3:03portion. So, if someone is considered to be a candidate for immunotherapy, doesn't have a comorbidity that would preclude it, I would absolutely give them immunotherapy? Absolutely. And Dr. Solomon, in the UK, has there been a paradigm shift and a movement away, obviously, from chemotherapy, chemotherapy for these patients? We want to. Availability is a bit more difficult, so we will probably need the results of Azoa 1, but we have been able to use compassionate use for being able to involve patients into trials. I've given a very positive view of the data, and the data is very positive, but having recruited quite a few patients and treated quite a few patients, there are patients that won't achieve a complete clinical response. And we have seen this, and the difficulty is not for oncologists in delivering the treatment mainly. It's usually very well tolerated.

4:03The difficulty is interpreting the endoscopic and particularly the radiological findings. So, things like, we're being asked to think about new things, so what does that mucin pool mean? It's not an entirely normal MRI, and actually, there's very little in the literature telling you that that abnormality is okay. So surgeons are understandably nervous about leaving a tumor in sight to, where you can see probably a post-immunotherapy change in an already mucinous tumor. But there are lessons that we as a community are going to have to learn, particularly after Resurone, is published. The stenosing complication is a real thing. I've had a patient who's stenosed in front of their primary tumor. So you couldn't actually see, you couldn't do surveillance of it, so they necessitated them having an operation. So the data looks 49 out of 49 patients. I suspect it's not going to be quite so straightforward. I think we always want that 100% CCR rate, and that's what made the New York Times what

5:06we also know that that's just not going to be realistic, and one of the things, we certainly at the University of Colorado, we have definitely moved to an immunotherapy, neo-adjuvant approach, which certainly makes sense in rectal cancer with the chance to have a CCR. But again, sometimes you're just not going to get a full CCR, and so at that point, you may have to move on to other standard of care therapies. As a practitioner, though, you want to hold on to that hope that they're going to get that CCR after a period of time, but we know it's not going to always be there. So in regards to some of these other questions that are coming up regarding duration, right, of therapy, the role of combination IO, IO, and rectal cancer. So for this patient, a 62-year-old gentleman with a stage 3 rectal cancer, no evidence of metastasis, again, MSI-high, deficient mismetropair, just as we had talked about neo-adjuvant immune checkpoint inhibition, what is the correct duration of therapy, right?

6:07And this is a question that comes up all the time, and I'll go back to you, Dr. Cohen, and just say, is there a strict amount of IO that you're going to do before making a call, and what is the right number there? I think we can say from the reported data that at three months, some patients have a complete clinical response, but far more likely at six months. I'll say in my own practice, if I'm treating someone off trial, I don't feel obligated to stop at six months if I feel like they've had a very good response, and maybe as you're describing, you know, you can't quite tell, is it or isn't it, having a complete clinical response? In those patients, I have sometimes kept going for a little bit longer while we're still trying to decide if we feel like overall we've had a good outcome, because at least here I would say it's relatively easy to get immunotherapy approved, and I've typically done single-agent immunotherapy just with the idea that perhaps the toxicity is a little bit less, and we haven't necessarily had any head-to-head data, but I think that'll be

7:10very interesting, is that some point would be moved to a shorter duration of a doublet rather than the single agent for six months. Yeah, to that point, Dr. Solomon, you had brought up this idea of being able to access some of these immune checkpoint inhibitors. When you're able to do that within the UK, have you chosen to go more single-agent checkpoint inhibitor, or are you trying more doublet? I mean, I think the spread of the data is, it's very difficult when there's far more data ironically in colon, but there are more patients with colon. Remember these, we don't see these people very often, and so it's very difficult to generate this data. The only thing I would say is that we can, we give six months, and you often then see patients moving from near-complete response to complete response two months later. So I think, you know, just hold your nerve. If you can deliver more IO, I think that's very reasonable if you can, then hold the nerve and do a repeat and doscopate, repeat MRI two months later. And many of those patients will have developed into a complete clinical response at that

8:14point. Dr. Cohen, this is a question that's going to come up and you can see how many providers are asking this question about CTDNA, and this is something that's going to come up in case after case that we discuss today, in today's program. So do you utilize CTDNA as part of the surveillance while you have somebody on IOT there before in the neo-adjuvant setting? I think you can, you know, I don't think your man data too, certainly the data does not say that we are wrong not to do it, but I think the data also suggests that CTDNA is exquisitely sensitive especially for immunotherapy response. We know that there's going to be fewer patients who are positive who have localized disease, but I do think that it can be a very powerful indicator for response. And outside of MSI high cancers, we see that the rectal cancer patients that are still CTDNA positive tend to have more localized disease as opposed to necessarily having concurrent metastatic disease at that time. So I think it can be a very helpful indicator, perhaps you have that near CR, and you're

9:19trying to decide, is it or isn't it? I think that having a CTDNA and following that quantitative level may be very helpful in that situation. Absolutely, yeah. And, you know, again, I think we'll learn more as we get more and more data, but I know it's just the field that's evolving very, very rapidly, but in some ways not rapid enough. So, you know, Dr. Sullivan, we had talked about complete clinical response, and certainly when we were able to get that, that's a phenomenal thing, especially when patients are going to be given an APR, and they can avoid that. They have a CCR after neo-adjuvant immunotherapy. You know, tell us about your protocol locally in terms of a watching weight and how that looks if patients are able to avoid surgery. I mean, what we know is that patients are most likely to recur within the first two years, but of course that's extrapolated from MSS, so actually we don't really know, because none of the patients have recurred. So we don't know when patients are most likely to recur, but we're basing the protocols

10:26for surveillance on the MSS patients. So they're quite intense in the first two years, and then it drops off. So at the moment, we've got three monthly scopes, and I think the imaging is every six months from the top of my head, and is that overkill, maybe? But I think, whilst we're developing the evidence base, I think we need to be cautious, because really we're keeping potentially a tumor in sight, too, which could be easily treatable by an endoscopic reception. So I think we do need to be conservative. The hope would be that maybe CTD enable all I was to back off a bit, but I don't think we're there yet. So you do need, the other thing you need is a motivated patient. This is not the right thing for all patients. Some patients will say, actually, you know what, I'd rather have an operation and get it out, rather than coming back every three to four months concerned about, and I'm living with the anxiety of not having had an operation.

11:27Yeah, you know, it's interesting, because the responses to immunotherapy can leave behind a certain amount of scar tissue, and you have brought this up in terms of like the obstruction that you may see sometimes with Iotherapy. I had a young woman that had MSI high rectal cancer, received a single agent immunotherapy, and was left with this mass, residual mass, that MRI called a locally advanced rectal cancer scope biopsy that even the biopsy was negative was like, this is definitely cancer. So she did end up going to surgery, and of course there's no cancer there. We've been fooled multiple times in this surveillance period, and even with MRI and flexible sigmoidoscopy can still be fooled. But we will learn from these patients, you know, that's the point. I think we've had a patient as well that we were nervous to call a complete, kind of full response because of some mucin pools, which apparently can take two years to resolve. So we will learn from these patients.

12:29We need to come together as a community, and we need to be very open about our outcomes and we need to publish and talk about this. This is an interesting situation. 44-year-old gentleman with stage two, MSI had colon cancer, wants to avoid surgery, right? So we're going to look at what we've seen with rectal cancer, open the closed monitoring with surveillance scope, CTDNA, and scans, and you have to keep in mind what this person is asking for is potentially Q3 month colonoscopies, right? Which is something that I'm going to talk about a little bit in my talk. But Dr. Cohen, any data to suggest that patients with MSI high colon cancer can avoid chemotherapy in this setting? I think it's really tricky. We know that, I mean, doing a colonoscopy at that frequency, I think, is not practical or viable, or at some point, you know, safe to go undergo that level of anesthesia and prepping and everything. But what the data says is, you know, we can look to Memorial Sloan, Kettering again, and

13:32in their all-comer trial, they saw, instead of the 100% responses that we were seeing for rectal cancer, they saw about 83% for colon cancer. And of the ones that failed, at least on what looked to have failed, I think half of them actually had viable tumor. So I think we know that there's no MRI in this space unless you have a very, you know, distal sigmoid cancer. So there's not really a good, as good of imaging modality, and you have endoscopy that's not as good. And so given the fact that not every complete clinical response is truly a pathologic complete response, I would say that I am at this point uncomfortable with nonoperative management. Yes, of course, there's going to be that patient that just is too sick for an operation, and we will end up learning through those patients. But in general, I don't recommend it at this time. And even CTDNA alone is not enough, because I think that we don't have a way of really proving the cancer is gone and monitoring it at any reliable frequency.

14:32Yeah. Dr. Selegman, your thoughts? I think this is an area that will develop, patients are asking, patients don't want to have an operation when they have no viable cancer cells. But again, it's the process of response assessment, and you've touched on this, in terms of it is more difficult with a colonoscopy, CT colon is much better actually than CT itself. But similarly, we need to look at this in a clinical study that looks at it in a practical way and actually gives real world data to then actually say, well, this was our intent to go down this road, and this is what happened. So there are trials that are actually ongoing in this space, and patients are asking for it. Yeah. So I think it's our duty to generate the data.

15:34Absolutely. And we'll wrap up with this one last one, just because I think it's such an interesting case. 56-year-old male with colorectal cancer, Lynch syndrome, and two isolated liver mats. Any data for immune checkpoint inhibitor, or is it better to try and do a chemotherapy immunotherapy combination? Now, there's very, very little data, certainly understandably, to answer this question. Dr. Cohen, very briefly, any thoughts about this? I think there's many right ways to treat this, and it's going to be different for different patients. I think when you have resectable disease, you could rationalize that. You could just go ahead and do the operation and be done with it. I think that you could give immunotherapy, I think we'll find out on Saturday if chemo immunotherapy is the right answer, or is an answer here. But when you have resectable disease, I think it becomes a lot more complicated. But you also have to think about this patient having Lynch syndrome, is that risk for other

16:37primary cancers? So I don't know. I think I would end up talking through with the patient. I don't think I have a blanket answer in this scenario. This concludes our program, special thanks to the faculty, and thank you for listening. This is Dr. Neolov for expert second opinion, optimizing the use of immunotherapy, MRD assessment, and novel approaches for patients with localized colorectal cancer.