Dr. Pedro Barata and Dr. Ugwuji Maduekwe discuss the evolving treatment landscape in gastroesophageal junction and gastric cancers, including the emergence of organ preservation as a selective therapeutic goal, as well as strategies to mitigate disparities in care. Dr. Maduekwe is the senior author of the article, "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Primetime?" in the 2026 ASCO Educational Book. TRANSCRIPT Dr. Pedro Barata: Hello, and welcome to By the Book, a podcast series from ASCO that features compelling perspectives from authors and editors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also the deputy editor of the ASCO Educational Book. Gastric and gastroesophageal cancers are the fifth most common cancer worldwide and the fourth leading cause of cancer-related mortality. Over the last decade, the treatment landscape has evolved tremendously, and today, organ preservation is emerging as an attainable but still selective therapeutic goal. Today, I'm delighted to be speaking with Dr. Ugwuji Maduekwe, an associate professor of surgery and the director of regional therapies in the Division of Surgical Oncology at the Medical College of Wisconsin. Dr. Maduekwe is also the last author of a fantastic paper in the 2026 ASCO Educational Book titled "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Prime Time?" We explore these questions in our conversations today. Our full disclosures are available in the transcript of this episode as well. Welcome. Thank you for joining us today. Dr. Ugwuji Maduekwe: Thank you, Dr. Barata. I'm really, really glad to be here. Dr. Pedro Barata: There's been a lot of progress in the treatment of gastric and gastroesophageal cancers. But before we actually dive into some of the key take-home points from your paper, can you just walk us through how systemic therapy has emerged and actually allowed you to start thinking about a curative framework and really informing surgery decision-making? Dr. Ugwuji Maduekwe: Great, thank you. I'm really excited to be here and I love this topic because, I'm terrified to think of how long ago it was, but I remember in medical school, one of my formative experiences and why I got so interested in oncology was when the very first trials about imatinib were coming through, right? Looking at the effect, I remember so vividly having a lecture as a first-year or second-year medical student, and the professor saying, "This data about this particular kind of cancer is no longer accurate. They don't need bone marrow transplants anymore, they can just take a pill." And that just sounded insane. And we don't have that yet for GI malignancies. But part of what is the promise of precision oncology has always been to me that framework. That framework we have for people with CML who don't have a bone marrow transplant, they take a pill. For people with GIST. And so when we talk about gastric cancers and gastroesophageal cancers, I think the short answer is that systemic therapy has forced surgeons to rethink what "necessary" really means, right? We have the old age saying, "a chance to cut is a chance to cure." And when I started out, the conversation was simple. We diagnose the cancer, we take it out. Surgery's the default. But what's changed really over the last decade and really over the last five years is that systemic therapy has gotten good enough to do what is probably real curative work before we ever enter the operating room. So now when you see a patient whose tumor has essentially melted away on restaging, the question has to shift, right? It's no longer just, "Can I take this out?" It's "Has the biology already done the heavy lifting? Have we already given them systemic therapy, and can we prove it safely so that maybe we don't have to do what is a relatively morbid procedure?" And that shift is what has opened the door to organ preservation. Surgery doesn't disappear, but it becomes more discretionary. Necessary for the patients who need it, and within systems that can allow us to make sure that we're giving it to the right patients. Dr. Pedro Barata: Right, no, that makes total sense. And going back to the outcomes that you get with these systemic therapies, I mean, big efforts to find effective regimens or cocktails of therapies that allow us to go to what we call "complete response," right? Pathologic complete response, or clinical complete response, or even molecular complete response. We're having these conversations across different tumors, hematologic malignancies as well as solid tumors, right? I certainly have those conversations in the GU arena as well. So, when we think of pathologic CRs for GI malignancies, right? If I were to summarize the data, and please correct me if I'm wrong, because I'm not an expert in this area, the traditional perioperative chemo gives you pCRs, pathologic complete response, in the single digits. But then when you start getting smarter at identifying biologically distinct tumors such as microsatellite instability, for instance, now you start talking about pCRs over 50%. In other words, half of the patients' cancer goes away, it melts down by offering, in this case, immunotherapy as a backbone of that neoadjuvant. But first of all, this shift, right, from going from these traditional, "not smart" chemotherapy approaches to kind of biologically-driven approaches, and how important is pCR in the context of "Do I really need surgery afterwards?" Dr. Ugwuji Maduekwe: That's really the crux of the entire conversation, right? We can't proceed and we wouldn't be able to have the conversation about whether organ preservation is even plausible if we hadn't been seeing these rates of pathologic complete response. If there's no viable tumor left at resection, did surgery add something? Are we sure? The challenge before this was how frequently that happened. And then the next one is, as you've already raised, "Can we figure that out without operating?" In the traditional perioperative chemo era, pathologic complete response was relatively rare, like maybe one in twenty patients. When we go to more modern regimens like FLOT, it got closer to one in six. When you add immunotherapy in recent trials like MATTERHORN, it's nearly triple that rate. And it's worth noting here, I'm a health services-health disparities researcher, so we'll just pause here and note that those all sound great, but these landmark trials have significant representation gaps that limit and should inform how confidently we generalize these findings. But back to what you just said, right, the real inflection point is MSI-high disease where, with neoadjuvant dual-checkpoint blockade, trials like NEONIPIGAS and INFINITY show pCR rates that are approaching 50% to 60%. That's not incremental progress, that's a whole new different biological reality. What does that mean? If we're saying that 50% to 60% of the people we take to the OR at the time of surgery will end up having no viable tumor, man, did we need to do a really big surgery? But the problem right now is the gold standard, I think we would mostly agree, the gold standard is pathologic complete response, and we only know that after surgery. I currently tell my patients, right, because I don't want them to be like, "Wait, we did this whole thing." I'm like, "We're going to do this surgery, and my hope is that we're going to do the surgery and there will be no cancer left in your stomach after we take out your stomach." And they're like, "But we took out my stomach and you're saying it's a good thing that there's no cancer." And yes, right now that is true because it's a measure of the efficacy of their systemic therapy. It's a measure of the biology of the disease. But should we be acting on this non-operatively? To do that, we have to find a surrogate. And the surrogate that we have to figure out is complete clinical response. And that's where we have issues with the stomach. In esophageal cancer, the preSANO protocol, which we'll talk about a little bit, validated a structured clinical response evaluation. People got really high-quality endoscopies with bite-on biopsies. They got endoscopic ultrasounds. They got fine-needle aspirations and PET-CT, and adding all of those things together, the miss rate for substantial residual disease was about 10% to 15%. That's a number we can work with. In the stomach, it's a lot more difficult anatomically just given the shape of people's stomachs. There's fibrosis, there's ulceration. A fair number of stomach and GEJ cancers have diffuse histology which makes it difficult to localize and they also have submucosal spread. Those all conceal residual disease. I had a recent case where I scoped the patient during the case, and this person had had a 4 cm ulcer prior to surgery, and I scoped and there was nothing visible. And I was elated. And on the final pathology they had a 7 cm tumor still in place. It was just all submucosal. That's the problem. I'm not a gastroenterologist, but I would have said this was a great clinical response, but because it's gastric, there was a fair amount of submucosal disease that was still there. And our imaging loses accuracy after treatment. So the gap between what looks clean clinically and what's actually there pathologically remains very wide. So I think that's why we're trying to figure it out and make it cleaner. And outside of biomarker-selected settings like MSI-high disease, in general, I'm going to skip to the end and our upshot for the paper, which is that organ preservation, I would say for gastric cancer particularly, should remain investigational. I think we're at the point where the biology is increasingly favorable, but our means of measur
