Video

Understanding Esophageal Squamous Cell Carcinoma: Pathophysiology, Knowledge Gaps, and Promising Developments

Karyn Goodman, MD, MS

In this video, Karyn A. Goodman, MD, MS, Professor and Vice Chair for Research and Quality in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai, provided insights into esophageal squamous cell carcinoma, covering its pathophysiology, early detection, knowledge gaps, emerging technologies, and preventive strategies.

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Transcription:

Karyn A. Goodman, MD, MS: My name is Karyn Goodman. I am a GI radiation oncologist at Icahn School of Medicine at Mount Sinai in New York.

Consultant360: Can you briefly describe the pathophysiology of ESCC?

Dr. Goodman: So esophageal squamous cell carcinoma arises usually from the cells lining the upper to mid part of the esophagus. It's a tumor that can grow and invade into the tissues around the esophagus. It can go to the lymph nodes and it can go to other sites in the body. It can metastasize, but this type of cancer is a little different from what is the more common type of esophageal cancer, which is the adenocarcinoma, which is more likely to be in the lower esophagus and into the gastroesophageal junction or the area right between the stomach and the esophagus. The esophageal squamous cell carcinomas are usually associated with a history of smoking and alcohol use. So we see this more often in some areas of the world. And globally we see it more in areas that our people smoke and drink, especially if it's higher incidents in places like China and France. In the United States it's about 30% of the cases of soft gene cancer that we see and has been decreasing in incidents as compared to the esophageal admin carcinomas.

C360: What are the most promising developments in the early detection or screening of ESCC?

Dr. Goodman: So in some places in the world, there have been attempts to identify esophageal cancer at an earlier stage. So, the approach in Asia has been to endoscopies earlier on. So patients are undergoing screening with endoscopies to identify either changes that might lead to cancer, like we call it dysplasia, things that might be a precursor to cancer or to identify an early stage cancer in the United States because the incidence of esophageal cancer is lower than it is in Asia. It hasn't been a really, has been a standard practice because it's not really, it's just not as common here on the expense of doing these endoscopies is quite high. But more recently there's some really exciting options like capsule that we put a capsule down on a string that can then be pulled up and can bring and has a little brush and then that can bring up cells. So that can be used as a screening device without having to do the full endoscopy. And so there's a lot of interest in doing these types of procedures that are less invasive than putting a patient under anesthesia and doing endoscopy. So I think those are going to be newer approaches that allow us to identify patients who may have dysplasia or even early cancer so that we can treat them and either avoid the cancer or treat them when it's an earlier stage.

C360: What is it that we still do not know about ESCC? What are the gaps in our knowledge that still remain?

Dr. Goodman: Well, I think it's still a cancer that is related to certain conditions that cause more inflammation in the esophagus. So smoking and alcohol can cause inflammation. Also, certain types of having swallowed ly can irritate the esophagus that can cause a higher risk of cancer. But yeah, it's still not, it's not known why one person who has drinks alcohol gets squamous cell carcinoma esophagus versus another who doesn't. So we don't really understand what that next step is that then causes cancer. We also don't know what the optimal therapy is. Unfortunately, esophageal cancer outcomes are not great. So the prognosis is somewhat core. So especially because oftentimes we don't diagnose it until it's more advanced. Esophageal swim cell carcinomas, like I said, are mostly in the upper and mid part of the esophagus when it's in the upper esophagus. Surgery is very difficult because you'd have to remove the larynx or the voice box if you did the big surgery up here. So we try to avoid surgery in those patients and generally try to do the treatment with chemotherapy and radiation alone. And we really are still looking at how to improve the outcomes with our therapies that exist. And also looking at how we can include newer therapies such as immunotherapy, new targeted agents, vaccines. So there are a lot of new things on the horizon.

C360: How do you see emerging technologies, such as AI or machine learning, influencing ESCC diagnosis, surgical planning, or treatment outcomes?

Dr. Goodman: So we use PET scan as a way to evaluate patients at baseline to do staging. This isn't new, but it does help us to establish whether somebody may have metastatic disease or not, what the extent of disease is. So that's often incorporated into the evaluation of a patient with a diagnosis of squamous cell carcinoma. The other things that are being used, there are newer techniques with MRI now to help us be able to look at even response to therapy. So there's newer functional imaging approaches with MRI that help us look at baseline tumor and then response to treatment. In terms of surgical planning, I would say that I, more and more we're trying to do something called prehab. So we're trying to get patients to do what we normally call rehabilitation, but we call it prehabilitation, where we have them taking more steps before surgery or during the treatment before surgery to make sure they're in good shape so they're not getting debilitated from their therapy so that they can't undergo surgery or that they tolerate the surgery better. So that's a big area of interest is trying to do the pre-habilitation and that means physical therapy, nutrition, doing all the things to help 'em maintain their strength.

And then in terms of the therapeutic options, I think a big area now that's growing is the use of immunotherapy. So we are really excited about the potential for immunotherapy to improve outcomes for patients with esophageal cancer, both in the metastatic setting and hopefully now more and more in the locally advanced setting. So one of the recent studies showed that if you gave patients pre-op chemo radiation and then surgery doing chemo or during adjuvant nivolumab, which was an immunotherapy agent for a year significantly reduce the risk of the tumor coming back. So this is very exciting. We're doing this routinely. And then there are a lot of new techniques and radiation that we're using. Proton therapy is something that's being used more and more for cancer to reduce the toxicities from the radiation, essentially reducing the risk of impact on the heart and lungs. And then finally there's some interesting new options being used to directly inject because you can get to the esophagus endoscopically to directly inject therapies into the tumor. So there's been an ongoing phase one trial, and that may be moving into a more phase two and phase three trials now. So yeah, there's definitely some excitement about how we can improve our therapies for esophageal cancer.

C360: Is there any ongoing or upcoming research on minimally invasive surgical techniques for ESCC that you’re particularly excited about?

Dr. Goodman: Well, I think there's been for many years, sort of a different approach to doing surgery for esophageal cancer, depending on where you went to have your surgery. So depending on the expertise of a surgeon. So minimally invasive esophagectomy is becoming more commonly used. So there were just some guidelines by the Society of Thoracic Surgery that came out showing that there is potential to use the minimally invasive approach for these patients. If you go to some surgeons, they still feel that the better approach is to do a open approach. You have better access to the lymph nodes and things like that. But I think using the robot and all of that has really improved the surgical techniques. I'm not a surgeon myself, so I can't really speak to the specifics, but I certainly hear a lot about the controversies about which one is the better approach. And there's a lot of competition between the surgeon to do it one way versus the surgeon to do it another way. But yeah, I think there's definitely more interest in using the minimally invasive approach now.

C360: Is there a final take-home message regarding ESCC that you'd like to discuss?

Dr. Goodman: Well, I think prevention is the most important thing. And with any type of cancer, if we can avoid it upfront, that's the best thing. Because once these tumors have grown and you're starting to have symptoms and they're diagnosed, it's usually pretty advanced. And so the therapy is pretty aggressive, and our outcomes are despite having aggressive therapy where outcomes are not ideal. So I think the main things I would say are reducing alcohol intake and avoiding smoking. Being attuned to your body and saying, oh, if I'm having something get stuck every so often, I probably should go get that checked out. If I'm having heartburn, if I'm having all these symptoms, it's a good idea to get evaluated by a doctor and to be able to identify something early. If you, you're diagnosed with any kind of an early stage, and this is not related to ESCC, but we know Barrett's esophagus is related to adenocarcinoma. So being aware of what your risk factors are and appropriately getting evaluated, you don't have to be seen every year, but maybe every couple of years being evaluated by a gastroenterologist.

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