Classifying and Treating NETs


Simron Singh, MD: When I’m looking at a neuroendocrine tumor [NET], the first thing I do is try to think about classification. I try to think about all the different factors that I’m looking at. What are some of the factors that you look at in your clinic when you’re trying to understand and classify these tumors?

Jonathan R. Strosberg, MD: So we’ve already talked about several of them, but there are lots of ways of categorizing neuroendocrine tumors. When you see a patient, you want to be able to put that particular patient into the appropriate framework. We talked about grade and differentiation. We talked a bit about primary site, which is obviously very important. Each of these tumors has unique clinical features, even tumors that are quite close to each other like ileum versus appendix. They’re both technically midgut but are very different in terms of clinical behavior. We consider functional or nonfunctional. In other words, is the tumor hormone producing or not? Sometimes that can be a bit ambiguous, and it can change over time. We look at tumor burden. Is the tumor burden high or low among patients with stage IV disease? Is it liver dominant or not? That’s very important because a lot of our treatments are liver directed. Are the tumors expressing somatostatin receptors uniformly? That’s important in terms of considering somatostatin analogues as well as radiolabeled somatostatin analogues. So all these various prognostic and predictive factors are important to establish at baseline, and they can help direct treatment.

What are your thoughts on the diversity of NETs and how it affects treatment? Do you have any other thoughts on that?

Simron Singh, MD: No, I think we probably practice in a very similar fashion. I think it’s important to recognize that the group of neuroendocrine tumors is incredibly heterogeneous—probably more so than any other malignancy that we normally treat. We have these slow-growing tumors, where the patient’s life span can be many decades. We also have these very aggressive carcinomas, where we really have to act quick. So I think it’s really important to spend time to get all your tests done to really properly classify and understand what kind of neuroendocrine tumor the patient has. Then you can offer that patient the best treatment and be able to give them the best possible outcomes. I think it’s really important to invest that time at the beginning to really understand the tumor.

Jonathan R. Strosberg, MD: Exactly.

Simron Singh, MD: Jon, are there any factors that would lead you to decide that the patient doesn’t need treatment to start, for which you’d want to take a watch-and-wait approach? What factors would lead you to that, if any?

Jonathan R. Strosberg, MD: When you take a watch-and-wait approach, you’re often referring to a patient with an incidental diagnosis—a patient who is not having symptoms. If the patient is having tumor-related symptoms, that patient needs to be treated. There are really 2 circumstances for which you might think of using a watch-and-wait approach. The first is for a small, localized tumor. In that case, we’re usually talking about a pancreatic NET that is smaller than 2 centimeters. There are accumulating data that suggest that low-grade pancreatic NETs incidentally discovered to be smaller than 2 centimeters can be safely followed, but you probably want to choose that strategy for a patient who is older and has comorbidities. For a young, healthy patient, the concept of lifetime surveillance is probably a bit risky and is not that attractive.

Simron Singh, MD: I think it’s important to follow up with the patients as well. It’s important that they come back and that you’re not going to lose track of them.

Jonathan R. Strosberg, MD: Right. In that circumstance, you’re basically debating to watch and wait versus provide a potentially curative surgery that has a lot of morbidity. Then there’s the incurable stage IV circumstance, where a patient might be given an incidental diagnosis as a result of undergoing a scan for a different reason. Here you’re trying to decide whether to start a somatostatin analogue or watch and wait. The appropriate patient for a watch-and-wait approach is really one who, again, is asymptomatic with no hormone-related symptoms and no carcinoid syndrome and probably has a relatively low tumor burden. For that type of patient, you can discuss whether to start treatment with a somatostatin analogue, which is low in risk but still involves some adverse effects, cost, and discomfort to the patient, or to take a watch-and-wait approach. Even though somatostatin analogues substantially prolong progression-free survival—we know that from the PROMID and CLARINET studies—there’s no evidence, as of yet, that says that starting treatment early affects overall survival. If you look at both of those studies, all patients pretty much crossed over from placebo, but there was no impact on survival. There’s no evidence that the watch-and-wait approach is harmful to patients.

Simron Singh, MD: One thing we should mention is that in the PROMID study, 50% of the placebo patients had progressed at the 6-month mark.

Jonathan R. Strosberg, MD: Correct.

Simron Singh, MD: So if we elect for a watch-and-wait approach, it’s important that we follow up with them. We have to realize that at least half of them, if not more, are going to progress at some point. We want to be able to initiate treatment at the right time.

Transcript Edited for Clarity

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