Panelists: Simron Singh, MD, Odette Cancer Centre; Jonathan R. Strosberg, MD Moffitt Cancer Center
Simron Singh, MD: Jon, what are the criteria for resectability? You mentioned that surgeons play different roles in both early- and late-stage disease. They play a unique role. So how do surgeons play that role, and what factors come into play?
Jonathan R. Strosberg, MD: You can think of it stage IV versus not stage IV. In early-stage disease, surgery should always be considered. As we said, for really small indolent tumors, a watch-and-wait approach can sometimes be taken. That’s usually not the approach for small-bowel NETs [neuroendocrine tumors], which tend to be malignant even if they are slow growing and small. However, this is sometimes an option for pancreatic NETs. For rectal NETs that are very small and superficial, sometimes endoscopic management is sufficient. But for most early-stage tumors, we’re talking about surgery.
For stage IV disease, we also think about surgery. We primarily think about it for well-differentiated tumors, usually more in low-grade tumors than intermediate-grade tumors. The standard criterion is to use it if it looks like at least 90% of the metastatic disease can be resected. Typically we’re talking about the liver rather than other organs, such as the peritoneum or bone. We also need to think about resection of the primary tumor, even in patients with stage IV disease. These patients will continue to have problems related to the local site, such as obstruction or bleeding or pain in the case, for example, of a small-bowel neuroendocrine tumor. In patients with metastatic small-bowel NETs, we’ll often recommend resection of the primary tumor. We do that much less for pancreatic NETs, particularly if a case involves the head of the pancreas. I think the data are a bit more controversial. And, of course, all of the data are nonrandomized and retrospective, which makes it hard to talk about these recommendations with a high level of certainty. But still, I think that the evidence suggests that long-term outcomes are good if most of the disease can be resected. Do you have any other thoughts on that?
Simron Singh, MD: No. I think we’re constantly understanding the role that our surgical colleagues can play, and I think the role of debulking surgery is very important.
Jonathan R. Strosberg, MD: Right.
Simron Singh, MD: For many patients it can range from anything from helping with their hormonal secretion and improving their quality of life to turning back the clock and slowly bringing that back. It’s integral to understanding the role surgeons can play. As you alluded to, one of the big questions that my surgical colleagues are struggling to answer is, what do we do with incidental rectal NETs when we find them? How do we excise them? How do we follow them, and what is the need for that? And for those smaller pancreatic neuroendocrine tumors, what patients are the appropriate ones to follow and potentially avoid doing a big surgery in?
Jonathan R. Strosberg, MD: We haven’t really talked about gastric NETs, but that’s a really interesting and poorly understood entity. The large majority of type 1 gastric neuroendocrine tumors are actually just small multifocal polyploid lesions that are associated with atrophic gastritis, for which the atrophic gastritis leads to a low-acid state that produces high levels of gastrin that stimulate these tumors. This is almost never a surgical circumstance, although sometimes we see patients inappropriately referred for surgery. The standard treatment is surveillance and endoscopic resection.
Type 2 is a bit more complex. Those are gastric NETs associated with gastrinomas, where the gastrin produced by the pancreatic or duodenal gastrinomas leads to these small gastric NETs. I won’t get into that because that’s quite rare and complicated.
Type 3 is the sporadic gastric NETs, which are typically managed surgically, although small ones can sometimes be managed endoscopically. It’s important for clinicians to be aware that there are these 3 types of gastric NETs that are managed completely differently.
What are your thoughts on the role that Gallium-68 dotatate plays, as far as selecting patients for surgery and other treatments?
Simron Singh, MD: This is one of the most exciting developments we’ve had in the past few years. Functional imaging or somatostatin imaging is so important in neuroendocrine cancer. We don’t have a full understanding yet of the complete role that it can play and where it can have an impact. For my surgical colleagues, it can help them map out disease. When they are doing surgery, they can make appropriate decisions based on the possibility or the spread of metastatic disease. They can also ensure that the surgery is as complete as it can be, rather than having to do repeat imaging. From our point of view, I think it helps us understand the biology of the disease. It helps us classify the disease. It also helps us stage the disease and determine if treatments such as PRRT [peptide receptor radionuclide therapy] or radioreceptor isotope therapy are appropriate. I think having all of that information come from 1 test is quite astonishing.
Jonathan R. Strosberg, MD: There have been some concerns sometimes that the Gallium-68 dotatate scan can inappropriately rule out surgery. For example, patients with resectable liver metastases that happen to have several small bone lesions may be excluded from surgery, perhaps inappropriately so.
Simron Singh, MD: What you are really discussing is stage migration. This is going to be a phenomenon in every cancer. I think these are realistic questions, but I think we need to keep in mind that these lesions may have been in our patients before. Maybe we just never knew about it. That’s why we’re still working on trying to understand the optimal use of Gallium-68, both to help with surgery and also to prevent unnecessary surgeries.