Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, our discussion is focusing on advances in screening and management of Barrett's esophagus and esophageal cancer. Joining me is Dr. Sri Komanduri. He's a Professor of Medicine in Gastroenterology, Hepatology and Gastrointestinal Surgery, and he's the Associate Chief of Gastroenterology and Hepatology at Northwestern Medicine.

Dr. Komanduri, it's such a pleasure to have you join us again. I'd like you to start by speaking a little bit about the prevalence of esophageal cancer. How significant of a problem is this, and what's the scope of the issue we're discussing here today?

Dr. Sri Komanduri: Thank you very much. I appreciate the invitation to have this discussion today. As you all are aware, April is also Esophageal Cancer Awareness Month, so the timing is absolutely perfect. The interesting piece and, unfortunately, not so much the happy ending part of our story is that we have become extremely innovative in the field of esophageal cancer, in terms of diagnostics, and especially prevention when we can find the disease in the form of what we call Barrett's esophagus.

However, as you all are aware that esophageal cancer and what you hear about it is one of the most deadly cancers and continues to rise at an alarming rate. The key factor here is that the vast majority of these cancers are detected late in their course. And once they're detected, the five-year mortality or death rate is well over 80% to 85%. And so, we don't have great therapeutic modalities to treat this cancer when advanced. That has pushed innovation and technology over the last five to ten years to help us understand how we can better identify patients earlier with what we call Barrett's-related neoplasia or early pre-cancerous change, and even more so, what's the actual problem as to why we can't identify the patients. And really, this comes to the denominator of patients that we are getting in. And we really have not had a screening program for esophageal cancer until the last couple years where that has slowly taken off and we're starting to look at some patients that may not have made it to a physician to start understanding if we can solve to why the denominator is not adequate to make a difference in this disease.

Melanie Cole, MS: Dr. Komanduri, I've always wondered, despite improvements in therapy, there's been a reduction in esophageal cancer as you were just discussing, but screening options, as you were just saying, we have colonoscopy for colon cancer. And once you know you're at risk, then you get those colonoscopies every bunch of years, whatever it is. We know if you smoke, then you can get a CT lung cancer screening. Why aren't we using endoscopy if we know that people are at risk? Is this a screening option? Is this the gold standard? Can you speak about this a little bit?

Dr. Sri Komanduri: Yeah, this is a tricky question. And as many are aware, the concept of screening is very much based on the prevalence of the cancer itself. And for many of our cancers that we deal with in gastroenterology, specifically esophageal cancer and even pancreatic cancer, these are not so common in the big picture. When you think about colon cancer, breast cancer and lung cancer, then when you start looking at what will the screening modality tell us? And so, identifying patients early with Barrett's esophagus, you could argue is very helpful, but the vast majority of patients with Barrett's esophagus don't develop cancer.

So with that being said, the low prevalence of development of cancer, but also the low prevalence of the cancer itself has kind of pushed back on the idea of screening for this disease, especially because of the cost of sedated endoscopy and patients have to, similar to colonoscopy, take time off from work, miss a day, and come in for this procedure.

With that said, what has come from this concept is we need something for sure, and we need to expand the pool of patients we might screen. So, the vast majority of patients who develop esophageal cancer actually don't have typical heartburn or reflux type symptoms that we talk about. And this has been sort of the misnomer or the urban legend around this cancer is that many patients don't feel heartburn or describe those typical reflux symptoms. And so, we need to start looking at patients who have true risk outside of gastroesophageal reflux. This really focuses on patients who are smokers, and perhaps the biggest piece of this is obesity. As with any other cancer, especially central obesity is very much our highest risk factor for esophageal cancer.

So, many places, including ours at Northwestern, have started to look at how do we screen patients who may not have typical reflux symptoms, but have other higher risk factors such as obesity. To that end, the idea of a sedated endoscopy being so costly has led us to this innovation around what can we do at point of care? What can we do that's maybe not as costly to the patient and to the healthcare system? And even that could be done in the office real time. And so, many tools that have come down the pipeline have been looked at. And we've adopted these into a high-risk screening clinic here in the Northwestern system. Some of those are what we call catheter-based screening tools. This involves swallowing of the patient of a capsule similar to a pill. And when you swallow, it's attached or tethered to a catheter that allows the technician to slowly pull the tool back up. As the capsule dissolves, it opens up into a little brush that can acquire cells and we can pull this out of the mouth. And it's something that we can do unsedated in about three to four minutes in the office. Actually, not that uncomfortable. I've done it myself so I can speak to it. But something we could consider as one of the screening tools. And that tool is called EsoGuard. It's available publicly.

We also have been looking at transnasal endoscopy at Northwestern, which is unsedated, but something you may have seen or had done at an ear, nose and throat doctor's office. But this is a disposable scope, we can advance through the nose down into the esophagus, under just topical anesthetic. And we can screen people at the very least to identify do they need a sedated endoscopy? Do they have Barrett's or not? And this allows us to get to a lot more patients faster.

The good news is that we've also developed a program at Northwestern where we have trained advanced practice providers like physician's assistants and nurse practitioners to perform transnasal endoscopy. And this is something we are particularly cognizant of because, as you would imagine, you can't really do this in the office and expect physicians to step away from patient care, and perform these transnasal scopes. So, having advanced practice providers do this also increases the potential for screening.

So, these are two of the different modalities. There's a lot more coming down the pipeline. I think the key piece to this question is really we need to expand our screening pool and start looking at patients who don't just have typical heartburn and reflux, and then offer them some of these non-invasive, less costly modalities that we could do in the office to start identifying more and more patients who can benefit from our treatment.

Melanie Cole, MS: Well, thank you for telling us really how Northwestern medicine is pioneering early detection for Barrett's and esophageal cancer. Is the GI world prepared for screening and identifying so many more patients with Barrett's? Tell me what you would see happening if you're using some of these techniques you just described and you're identifying more people with Barrett's.

Dr. Sri Komanduri: I think one of the key pieces to the screening puzzle, and this has happened in colon cancer, it's a good analogy, is what do we do with what we find? So, yes, you can identify a lot more patients with Barrett's. You can identify more patients with Barrett's and precancerous changes or dysplasia. Then, we need people to act on this. And some of these are just seeing the patients. Some of these are who's going to do all the endoscopy? And then, who's going to do the treatment? And do we have enough trained, gastroenterologists to handle the volumes that would subsequently arise from this?

We saw this a little bit with a Cologuard phenomena in colon cancer and that has taken some time. But now, there are centers that just have blocks of endoscopy focused on patients with positive Cologuards. And so, it's taken some effort, but it can be done. And I think, as we train and as gastroenterologists get more focused on some of these newer areas to advance their career, so to speak, we will need some people to take on the success of endoscopic therapy for Barrett's esophagus and perform some of these things that they can get trained on and they don't need to have any advanced training during fellowship. And they can provide some additional services that they may not for these patients. More importantly, just getting these patients in and seeing them in the office and then doing surveillance endoscopy.

One of the key pieces that will arise is, when we find more patients with Barrett's esophagus, you're going to find a lot more patients who have non-dysplastic Barrett's esophagus or without that precancerous change, so to speak. And what are we going to do with them? Because right now, we have a glut of these patients that we just keep doing endoscopy every few years for surveillance. And so, this is again where innovation steps in.

And over the last few years, we've been working with a technology called TissueCypher. And TissueCypher is a nice way to bring together all the molecular changes that drive the cancer, the carcinogenesis of Barrett's to esophageal cancer. And it really takes all those together from the biopsy specimens. And then, using an AI algorithm gives us a report card of sorts or sort of an objective assessment for the patient of risk. And really, what's going to become important is if we start screening programs, we need to have better risk stratification. Some of that can be done clinically, but tools like TissueCypher have become standard of care. And in these patients, especially if they have some clinical risk associated with the Barrett's, like they're very young in age, they are obese, they are smokers, we can then send this risk stratification tool. And the key to that is that we take action on the result. So, you don't want to be doing more and more testing without really taking action on what you find. And so, what we have identified is, if patients have very low TissueCypher scores, their cancer risk is almost zero. And we can all either extend their surveillance intervals with endoscopy or even eliminate it in an older population.

On the other end of the spectrum, if you have a non-dysplastic Barrett's patient who has a very high-risk TissueCypher score, we can have a discussion with them about endoscopic eradication or treatment with tools like radiofrequency ablation, which are, as I said at the outset, super effective and have nearly a hundred percent cure rate for eradication of Barrett's esophagus in early dysplasia. So, the cool part of this is we've perfected the treatment. So if we do identify a lot more patients, we do need to put some sort of a risk stratification mechanism in place because then we can take action and help these patients.

The thinking here is that if we can treat some of those patients early, these are the ones that we might be missing in the bigger picture of why the esophageal cancer rates, while slightly decreasing, haven't really been impacted significantly by our successes in therapy.

Melanie Cole, MS: That's so interesting. Dr. Komanduri, can you discuss a case where TissueCypher for patient risk stratification, as you were just discussing, has made an impact on your patients?

Dr. Sri Komanduri: Absolutely. So, fortunately, I think not just as part of data, but in real practice, we see the impact and I've seen the impact in my practice. We've had at least a couple, but one particularly comes to mind of a very young gentleman in his early 40s, who had what we would call typical clinical risk with a first-degree relative who had esophageal cancer at a little bit of an older age in the 60s.

So, if you really go by the current set of guidelines without risk stratification, there really is no true support to do anything more for this patient besides performing surveillance, or at least just taking a look at their esophagus every few years. So in this patient, we did an endoscopy, because of the risk and he did have some reflux symptoms that were mild. And That demonstrated a very long segment or more than a few centimeters of Barrett's, but about five centimeters of disease. We took biopsies, all came back as non-dysplastic Barrett's. And in which case, as I said, we wouldn't do too much. We did send his pathology for TissueCypher, and it came back extremely high risk, with a five-year potential cancer risk of over 50%, which is pretty alarming in a young person like that. And one of these are situations where we may delay or actually end up in a situation where we get an interval type of cancer that develops between the surveillance intervals because of the aggressiveness of this disease. And we would not have known that without this risk stratification tool.

So in his case, we went on and treated him with radiofrequency ablation and cured his Barrett's. And now, his risk is theoretically close to zero despite the genetics that have played a role. So, I think this is one example of many we've seen through myself and my colleagues where we alter what we might have done by traditional standards of practice.

Melanie Cole, MS: Well, thank you for sharing that. And Dr. Komanduri, you mentioned interval cancer. Can you speak a little bit more about that in post-endoscopy esophageal neoplasia. How significant are these, and what solutions might reduce missed lesions?

Dr. Sri Komanduri: Over the last, I'd say five years, we've really come to understand these concepts of post-endoscopy esophageal cancer or neoplasia. And what that really simplifies into, again, the analogy goes to colon cancer, where there is a significant rate of people developing cancer in between when they were given these surveillance intervals. So, let's say you were told to come back in five years, there are a subset of patients that develop cancer in between, and that's very scary.

Similar to the Barrett's side, when we are generally recommending these three years, and in some cases up to five years of surveillance intervals, we are seeing up to about a 13% to 14% rate of interval cancers developing, meaning that patients are getting cancer or even high-grade dysplasia when we talk about neoplasia in that three-year interval. So, they come back for some other symptoms they can't swallow or they're having anemia or other things. And we scope them and they have actually advanced disease.

So, these are areas where we have to improve ourselves. We talked about this denominator issue and the ability to find more patients. It's also paramount and critical that, if we're finding more patients, even the patients we have, the exam we're doing with endoscopy has to be very, very airtight. You can't miss things as we're going along.

One of the key things that we've developed over time is what we call a high quality exam or sort of a set of criteria of what we think every physician should do as they pass an endoscope down a patient with Barrett's esophagus. And some of that's very intuitive. You know, taking a look for the right amount of time. And a lot of this is based on identifying what we call visible lesions. That's where we get into trouble. The esophagus is very contractile and emotional at times. And so if you don't put the adequate time in and really look, not only with the high-definition white light, which we use with endoscopy, but something called narrow-band imaging, which is our version of a blue light technology that highlights certain areas that are of high risk. And we're really just looking for spots that look very different than the others. So, it's not about a growth or an ulcer or something very evident. While those are visible lesions, we're also looking for areas that may be flat that just look altered by these different lights. And then, when we take our surveillance biopsies, we need to target those areas so we know where there might be some early neoplasia. I think if we continue to improve as a specialty at this and really focus on the high-quality exam, we can really address these interval cancers.

Melanie Cole, MS: Where does GERD fit into all of this? Are there specific considerations that you would recommend for patients and other providers who have patients with Barrett's esophagus?

Dr. Sri Komanduri: One of the most critical pieces to the development of Barrett's and esophageal cancer is the continuum of disease. And that really starts with gastroesophageal reflux. And I think for even us as gastroenterologists, we have to remember that really just means stuff's coming up and down the esophagus. And it's not a one-to-one relationship with symptoms. So, vast majority of patients who even have gastroesophageal reflux don't always feel heartburn or the typical symptoms. So, we need to keep that in the back of our head. So when we see our patients, we're treating them, whether that's with acid suppressive medicines. And in a lot of cases, it's actually just a mechanical issue where stuff's coming up and down and they have a hiatal hernia or they have just a big gap where the diaphragm usually pinches the stomach and esophagus.

What we found at Northwestern is mechanical barrier reconstruction or doing a surgical or endoscopic anti-reflux procedure in these patients such as LINX or what we call TIF, transoral incisionless fundoplication, have really made an impact in these patients because you're just closing the door. And I think you don't even need to be in the medical field to understand that, but when the door is too wide open, stuff's always coming up and down. And even the acid medicines we put down there only control to a certain extent.

So in this type of patient who's had severe reflux developed Barrett's, a complication of reflux and even early cancer. We want to consider in all patients does the barrier pose a big problem for this to come back or be a long-term issue. So besides acid suppression with medications, we do offer all these patients a consideration for a surgical or endoscopic anti-reflux procedure. And our data suggests that once you do that, not only do they get off their medicines, the chances of the disease coming back is almost zero.

Melanie Cole, MS: Wow, this is really such an interesting and important conversation we're having. And finally, Dr. Komanduri, you're on the board of Directors for the Esophageal Cancer Action Network, ECAN. How does this play a role in supporting both physicians and patients? I'd like you to wrap it up for us with a summary and tell us about ECAN and the importance of knowing this and the awareness for other providers.

Dr. Sri Komanduri: One of the biggest things for us as physicians is ensuring our patients have the proper advocacy and resources. When we make a diagnosis, and especially when we're getting in the world of cancer, whether pre-cancer with Barrett's esophagus or all the way to esophageal cancer, often physicians are moving very quickly and we don't think about all the resources the patient might need and who can advocate for them. Many times for patients, some of the most difficult decisions are just finding access to care to whether it's gastroenterologists, surgeons, oncologists, and this is where organizations like ECAN really hit the home run.

I've had the pleasure of serving on the board for the Esophageal Cancer Action Network. And one of the things that we do really well is ensuring that when patients get to us, we do provide that type of advocacy, whether that's getting them to people who are like them to really get them into proper groups to have discussions or even more to the right doctors. And I think that's where we do that through information. We do it through educational sessions, but we also do it through things and different tools that we're trying to develop. And one of those is something that's been done in the pancreas cancer world. We're starting to establish a criteria for patient advocacy around centers of excellence. And the idea of that is that patients could go to a website and identify wherever they are in the country, where they might go close to them for a center that really focuses around all the aspects of Barrett's esophagus, esophageal cancer, and get into the right doctors. Part of it is just getting into someone quickly for a lot of these patients. And so, we want to provide that tool not only for patients, but also for physicians to recommend to their patients.

The last piece, at least from my side as a physician, we may not directly be educated by patient advocacy organizations, but by directing our patients to them, they often answer a lot of those difficult questions that we either don't have the bandwidth or we don't have the ability to answer. And whether that's around finding doctors, patient-level education around reflux, Barrett's, esophageal cancer, or even other things like what should they do about their diet, they're having trouble coping, their family members, you know, where can they get support? There's so many aspects around the cancer continuum that are critically dependent on patient advocacy, and I think sometimes as physicians we lose track of that. So, organizations like ECAN are really critical.

And as we move forward, we've talked a lot today about a lot of exciting innovation, a lot of things to help screening, and identifying patients at risk for esophageal cancer faster, tools to help us improve our detection of early cancers and treat them effectively and, ultimately, advocating for our patients. Organizations like ECAN really do help not only on that support front for the patient, but also advocating for new innovation for physicians to understand what's available to them and what they might do to take better care of their patients.

Melanie Cole, MS: Beautifully said. Thank you so much, Dr. Komanduri. What a great guest you always are. So informative and you're such a great educator. Thank you so much for joining us. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/gastroenterology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.