Appendix Cancer Awareness Month With Thomas Abrams, MD

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we're having this interview in honor of Appendix Cancer Awareness Month, and I'm joined by our Editor-in-Chief, Dr. Thomas Abrams.

Thomas Abrams, MD: Thank you so much for having me, Keira. It's always a pleasure to give a little bit of an overview of a disease I treat and that I see a lot of patients with. Appendiceal cancers are a rare group of malignancies, and we just don't see enough of these patients to build up enough of a clinical trial repertoire to really know how to treat these diseases specifically, like we do for colon cancer and pancreatic cancer, where we see a very, very significant number of patients. But what I want to do is give a very quick overview of the four distinct types of appendiceal cancer and then kind of take you through how we treat each one.

The most commonly found appendix cancers are found incidentally during an appendectomy. Someone comes in, and they have what's felt to be acute appendicitis. They have an appendectomy, and then two weeks later, they follow up with their surgeon, and the surgeon says they found some cancer in the appendix. So, what kind of cancer? Well, most of the time, it's going to be a colonic-type adenocarcinoma, sort of similar to what you would find in the colon. These cancers would be treated exactly like colon cancer because we don't really have enough of a critical mass of patients to trial patients with appendiceal adenocarcinoma alone, so we extrapolate from the colon cancer data.

If it's a very small tumor, then surgery alone should be sufficient. If the tumor looks to be more invasive in the appendix, then typically we would recommend a right hemicolectomy, a second surgery that would sample the nodes and take out part of the right colon. If there's additional disease, then that's very valuable because you're removing it, and then potentially giving chemotherapy afterwards adjuvantly.

But that's not all that can happen, because adenocarcinomas comprise only about 60% of these cancers that are found incidentally. You also can have what's known as a mucinous neoplasm, which is not even cancer. These so-called low-grade neoplasms are really composed mostly of mucin and very, very low cellularity. These are the patients that will sometimes present with pseudomyxoma, which is something called jelly belly. Their bellies get big with jelly. What happens is that these appendiceal mucinous neoplasms, before they can be removed, can explode and then shower the abdomen with mucin. Then over time, that may have happened microscopically, but over time, the belly starts to accumulate this mucin.

A surgeon has to go in there and physically get that goop out. Sometimes what they can do is really try to get all of the goop and the cells out of the nooks and crannies, and then they can instill heated chemotherapy into the abdominal cavity, with the idea of trying to get rid of whatever other cells are in there. It's definitely something that can work in low-grade disease, but oftentimes the cancer's still going to come back. But those patients can live for years and years because it is a very low-grade quasi-malignancy.

Then you can have neuroendocrine tumors. These are carcinoid tumors, and they can range from very low-grade to higher-grade, and oftentimes surgery is going to cure those. But if they do come back, oftentimes they'll come back in the liver, and they can cause something called carcinoid syndrome, which is a release of serotonin and serotonin-like substances into the blood stream. This can cause the characteristic findings of carcinoid syndrome, which are flushing, diarrhea, and sometimes shortness of breath and wheezing. We use somatostatin blockers to alleviate those symptoms and slow the progression of disease.

So, it's a wide range of diseases, and there are so many different potential scenarios that can happen. It's important to get the message out there that these cancers not only exist, but they are not as uncommon as we think they are. Most of the time, because they're found incidentally and they're small when they're found, generally speaking, patients do very well. But in advanced disease, when patients have widespread disease, widespread adenocarcinoma, we treat it just like colon cancer. We give chemotherapy, and we're trying to forestall the progression of disease, extend survival, and preserve quality of life for as long as possible.

Oncology Data Advisor: Thank you, that was a really helpful overview of all the different subtypes. I'm sure there are so many different considerations with all the different presentations. How do you personally approach treating these patients in your practice?

Dr. Abrams: When I see a patient, sometimes they're referred to me from the surgeon who does the simple appendectomy, and they just want me to evaluate the pathology and see if I recommend additional surgery or something else. With those patients, I will talk about the pros and cons. Sometimes, for some subtypes of cancer, the recommendations may be different depending on which society you're looking at. For appendiceal carcinoids that are between one and two centimeters, the North American recommendation is potentially doing a right hemicolectomy if there are some high-risk features, but the European societies say, "Just watch it, it should be fine."

In those instances where you have those conflicting recommendations, you have to tell the patient, "We don't really know the right answer. There's expert opinion here, and we'll offer both, but you'll have to pick." And that's a very tough situation. So, I like to offer patients my own expertise and say, "Hey, I think if I were you, I'd probably just be okay with watchful waiting. I don't think you really need a right hemicolectomy here, knowing that it's not 100% and there's no way to guarantee an outcome." I think it's important to give your own opinion when you're seeing patients with more widespread disease, when you're talking about giving systemic therapy.

For patients with adenocarcinoma that may be metastatic, you're going to treat it like colon cancer. You give your FOLFOX (leucovorin/fluorouracil/oxaliplatin) or your FOLFIRI (leucovorin/fluorouracil/irinotecan), and you do molecular testing to see if they're candidates for other types of treatments. If it's carcinoid, typically you'll start with an SSA, a somatostatin analog, and you'll do a dotatate positron emission tomography (PET) to see what the uptake is and where the disease is. If the SSA is not necessarily holding the disease at bay, you may go to a clinical trial, or you could treat with lutetium Lu-177 dotatate (Lutathera^®).

There are a lot of different options, and you see patients through the whole way. Then if a patient has a mucinous neoplasm, you might send to a surgeon for consideration of cytoreductive surgery and hypothermic intraperitoneal chemotherapy (HIPEC). There are just a ton of different potential ways to treat appendiceal cancers. It's a very therapeutically rich disease because there are just so many different ways to treat and so many different considerations. But I think the message is that patients can do very well even in advanced disease. Some patients are going to live a very long time, especially with carcinoids and mucinous neoplasms.

Oncology Data Advisor: That's great. So, I know you mentioned there isn't as much ongoing research in appendix cancer just due to the rarity of the disease. Are there any future directions in research or treatment that you think might be coming down the pipeline in future years?

Dr. Abrams: I think that as we learn more about carcinoid tumor—and there's a ton of research in carcinoid tumor—we are definitely improving outcomes, and appendiceal carcinoids are not an uncommon sort of brand of carcinoid tumor. I think we are definitely moving in the right direction. We have a therapy that was approved within the last four years called lutetium Lu-177 dotatate, which is basically an SSA with a radioactive payload. You're basically combining the best therapy for carcinoid with radiation. It's like a one-two punch that has really improved the outcome of patients with advanced carcinoid tumors, including those arising from the appendix.

I think in the adenocarcinoma realm, as colon cancer treatments evolve and we learn more about colon cancer treatments, the appendiceal adenocarcinomas are evolving as well. I think we've certainly not come as far in new treatments for colorectal cancers, except at the margins for microsatellite instability– (MSI)–high disease and things like that, and we don't typically see that very often in appendiceal cancer. Appendiceal adenocarcinomas tend to be treated in a very vanilla fashion, with your FOLFOXs and your FOLFIRIs and bevacizumab. That's sort of where we're at for the most part, but do I think that we're going to learn more and eventually break down the barriers with respect to immunotherapies? Absolutely.

With respect to the mucinous neoplasms, these are not diseases that are typically responsive to systemic therapy because they're so low-cellular. Surgery is really the chief therapy, and I think it always will be. I think those are the avenues for improvement in outcomes here, just taking the diseases that they are most like and moving forward there. But I do think that there are some differences with respect to appendiceal cancer. We do see more signet ring histology in adenocarcinomas from the appendix than we do in the colon, and those tend to be more aggressive. They can be very difficult to treat. There are additional considerations, but that just makes it a little bit tougher. It doesn't make it impossible.

Oncology Data Advisor: In light of August being Appendix Cancer Awareness Month, what would you most like to share about this disease in hopes of raising more awareness for it?

Dr. Abrams: It's an organ that most people just don't really know much about. They only know something about it when it goes off and they get appendicitis. I think one of the things that would help is before a surgeon takes a patient to the operating room for an appendectomy, they could say, "I don't think this is going to happen, but there is an off chance that the appendicitis that we're operating on is actually going to show a cancer." Because the fear that is generated from an unexpected cancer diagnosis after an appendectomy is incredible. Patients that I see who have gone through this, they are amongst the most nervous of any patients you're going to see.

I think just to allay their fears and set the expectation that, "Hey, there's a chance that we're going to see this, but I don't think it's going to happen," I do think that's a good message for our surgical colleagues to communicate before the surgery actually happens. That way, when that pathology report comes in that shows the cancer, it's not the first time they're hearing that it's even possible. And I want patients who are dealing with this disease to know that we're working hard, and we're trying to improve the outcomes for patients with these diseases.

Oncology Data Advisor: Definitely, and it's great that we have this month to shine a little bit of a light on it and get these messages out there.

Dr. Abrams: Absolutely.

Oncology Data Advisor: Thanks so much for coming on today to talk about this. I'm glad that we can spread this information.

Dr. Abrams: It's my pleasure. Thanks, Keira.

About Dr. Abrams

Thomas Abrams, MD, Editor-in-Chief of Oncology Data Advisor, is an Assistant Professor of Medicine at Harvard Medical School, an Institute Physician at Dana-Farber Cancer Institute, and Director of the Liver Cancer Task Force at Harvard Cancer Center. He specializes in the treatment of patients with gastrointestinal cancers, including pancreatic, gastric, colorectal, esophageal, gallbladder, anal, primary liver, and appendiceal cancers. Dr. Abrams' primary research interest is the early detection of liver cancers through the discovery and application of novel biomarkers.

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.