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The Role of Surgery in the Management of NETs

Insights From:Jennifer Eads, MD, Case Western Reserve University; Matthew H. Kulke, MD, Harvard Medical School; Diane Reidy Lagunes, MD, Memorial Sloan-Kettering Cancer Center; Eric H. Liu, MD, FACS, Rocky Mountain Cancer Center; James C. Yao, MD, The University of Texas MD Anderson Cancer Center
Published: Wednesday, Mar 23, 2016


Transcript:

Matthew H. Kulke, MD:
Let’s go back and talk a little bit about the role of surgery and about the individualized approach to patients. Eric, when there’s localized disease and it can come out, that’s a no-brainier. But there are other situations where patients may benefit from surgery, whether they have metastatic disease with curative intent or even palliative intent. How do you sort that out?

Eric H. Liu, MD, FACS: That’s exactly right, Matt. Essentially, I always say the patient who left my office is going to be very different from the patient who is about to walk in. We think about them in a very individualized way, which is why we have these multidisciplinary discussions. But when it comes to surgery, you’re right. Part of my job is to say, “Well, what can I do safely? What can I remove?” And then the second thing is, “How am I helping this patient?” And so the criteria for thinking about it is: is there going to be some complication which will hurt this patient down the road? Are they going to have a small bowel obstruction? And doing a small bowel resection or a colon resection is a safe operation now. So if I can do it when they’re healthy and strong, this is the time to do it.

But there are some complications with some of the pancreas and small bowel tumors. Small bowel tumors, for example, tends to spread to the mesentery, and that can be really quite challenging because they can get this desmoplastic reaction. And when they do, chronic small bowel obstruction is a huge problem. We try to resect those and get those cleaned up as much as possible early on before it can progress. But as far as some of the other lesions, say you have discrete lesions in the liver: those patients may do very well with a debulking operation. And the neat thing about it is, in addition to our classic surgical approaches of resection, we can actually do a lot of things. There’s ablative technology. There’s even irreversible electroporation, which is a new technology using voltage fields to treat these things.

With the new surgical therapies, there are a lot more options. And something we also forget, too, is lung NETs. Bronchial carcinoids are also relatively common, almost a quarter of our neuroendocrine patient population. So doing good lung surgery, making sure we use the proper technology, either video-assisted thoracotomy or even just good old-fashioned open surgery and doing a good lymphadenectomy, is also part of the armamentarium.

Matthew H. Kulke, MD: In other types of cancers, where there are high response rates to chemotherapy, we often talk about downstaging patients prior to surgery. Diane, is that ever something you think about? If there’s ever a borderline case, do you ever think you can downstage it?

Eric H. Liu, MD, FACS: Can you make my life easier? That’s what I want to know.

Diane Reidy Lagunes, MD: Well, just to follow up on that last point: when we talk about debulking, one could do regional therapies with embolizations, as well.

Eric H. Liu, MD, FACS: Absolutely.

Diane Reidy Lagunes, MD: I think a lot of times the idea of surgery sounds like it’s going to result in better outcomes for patients because maybe you’re going to remove as much as possible. But, in fact, a regional approach to embolization can be very safe, and depending on the type of embolization that you select, can often be done repeatedly. So it’s something to consider. But the question of neoadjuvant therapy is a great one. One can define that in many different ways. Presumably, you can even embolize in a neoadjuvant setting.

And then traditionally, at least in other cancers, we use cytotoxic chemotherapies. With targeted agents and somatostatin analogs, the role could probably be questioned using them first. It’s unlikely that it would shrink the cancer in that respect. But particularly with pancreatic neuroendocrine tumors, if you have a tumor that has not metastasized and looks to what the surgeon would call borderline, many times we have considered temozolomide-based therapy in those patients in efforts to shrink that cancer and then have it removed potentially for curative intent. There certainly is a role for neoadjuvant therapy, but it’s a little bit more limited in our disease.

Having said that, an approach of not jumping into surgery, before doing so even with the test of time, is often something that more we do frequently. For example, in our disease, you may have what looks like an isolated liver metastasis. But what if, for example, it may require right hepatectomy, which is a big deal for our patients? Do you want to jump in and do that? Or maybe it’s more of an intermediate grade tumor where we want to “reset the clock” but maybe the biology just won’t let us do that. The test of time in a neoadjuvant approach may be very helpful for the patient, so that we’re not inappropriately jumping into surgery and potentially hurting the patient.

Matthew H. Kulke, MD: You mentioned embolization, and one really tough question that comes up a lot is when you have a patient with three, four liver metastases, should they be embolized or should they get debulking surgery? Eric, you want to start off with that?

Eric H. Liu, MD, FACS: Yeah. I actually have pretty strong feelings about that, because with the embolization techniques we have now, maybe in a setting of an aggressive type of adenocarcinoma, they may not survive long enough to see the long-term consequences. We’re talking about radioembolization, bland embolization, chemoembolization, your choice. Since our patients live for a long time, we can actually see these long-term sequalae, so it is something to think about. You want to make sure you choose the right therapy. If you’re taking three or four tumors, which are maybe possibly well behaved, maybe you don’t want to subject the liver to all that.

The good thing is that surgery is still a very effective therapy. If they’re round, discrete, they can either be enucleated or just wedged out. It can be done very, very safely with our new therapies. But if it tends to be a little more military—4 lesions, 25 lesions—I can remove them, but 1000 lesions I can’t remove. That may be a more useful setting for a more diffuse type of therapy like embolization.

Diane Reidy Lagunes, MD: I agree that radioembolization for our disease, I get a little worried about using, because we don’t know the long-term effects We’ve used bland embolization for a couple of decades, and in the setting of progressive disease, the benefit is that you are treating the whole liver. I think most of us recognize that when you’re really removing those three to four tumors, we know that there’s more there. So it is absolutely not curative. Can you avoid maybe or can you allow yourself to reset the clock by doing that?

Maybe, but that is why it’s so important to go to these big centers or have these multidisciplinary teams to better define each patient because everyone is so different. If I may add, too, part of that importance is really having good imaging. Everyone relies on CT scans, and it’s great and well proven, and you can do it quickly and relatively inexpensively, but there are certain technologies which are more sensitive for liver lesions, say an MRI with diffusion weighted. And this new imaging technology, which is coming soon hopefully, this gallium technology, may pick up lesions maybe not even in the liver but maybe just a bone metastases. Maybe I don’t necessarily want to do a Whipple in someone if they have multiple bone metastases, so it’s just something to consider. Part of that individualization, those criteria, is having good data and good information to start with.

Transcript Edited for Clarity
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Transcript:

Matthew H. Kulke, MD:
Let’s go back and talk a little bit about the role of surgery and about the individualized approach to patients. Eric, when there’s localized disease and it can come out, that’s a no-brainier. But there are other situations where patients may benefit from surgery, whether they have metastatic disease with curative intent or even palliative intent. How do you sort that out?

Eric H. Liu, MD, FACS: That’s exactly right, Matt. Essentially, I always say the patient who left my office is going to be very different from the patient who is about to walk in. We think about them in a very individualized way, which is why we have these multidisciplinary discussions. But when it comes to surgery, you’re right. Part of my job is to say, “Well, what can I do safely? What can I remove?” And then the second thing is, “How am I helping this patient?” And so the criteria for thinking about it is: is there going to be some complication which will hurt this patient down the road? Are they going to have a small bowel obstruction? And doing a small bowel resection or a colon resection is a safe operation now. So if I can do it when they’re healthy and strong, this is the time to do it.

But there are some complications with some of the pancreas and small bowel tumors. Small bowel tumors, for example, tends to spread to the mesentery, and that can be really quite challenging because they can get this desmoplastic reaction. And when they do, chronic small bowel obstruction is a huge problem. We try to resect those and get those cleaned up as much as possible early on before it can progress. But as far as some of the other lesions, say you have discrete lesions in the liver: those patients may do very well with a debulking operation. And the neat thing about it is, in addition to our classic surgical approaches of resection, we can actually do a lot of things. There’s ablative technology. There’s even irreversible electroporation, which is a new technology using voltage fields to treat these things.

With the new surgical therapies, there are a lot more options. And something we also forget, too, is lung NETs. Bronchial carcinoids are also relatively common, almost a quarter of our neuroendocrine patient population. So doing good lung surgery, making sure we use the proper technology, either video-assisted thoracotomy or even just good old-fashioned open surgery and doing a good lymphadenectomy, is also part of the armamentarium.

Matthew H. Kulke, MD: In other types of cancers, where there are high response rates to chemotherapy, we often talk about downstaging patients prior to surgery. Diane, is that ever something you think about? If there’s ever a borderline case, do you ever think you can downstage it?

Eric H. Liu, MD, FACS: Can you make my life easier? That’s what I want to know.

Diane Reidy Lagunes, MD: Well, just to follow up on that last point: when we talk about debulking, one could do regional therapies with embolizations, as well.

Eric H. Liu, MD, FACS: Absolutely.

Diane Reidy Lagunes, MD: I think a lot of times the idea of surgery sounds like it’s going to result in better outcomes for patients because maybe you’re going to remove as much as possible. But, in fact, a regional approach to embolization can be very safe, and depending on the type of embolization that you select, can often be done repeatedly. So it’s something to consider. But the question of neoadjuvant therapy is a great one. One can define that in many different ways. Presumably, you can even embolize in a neoadjuvant setting.

And then traditionally, at least in other cancers, we use cytotoxic chemotherapies. With targeted agents and somatostatin analogs, the role could probably be questioned using them first. It’s unlikely that it would shrink the cancer in that respect. But particularly with pancreatic neuroendocrine tumors, if you have a tumor that has not metastasized and looks to what the surgeon would call borderline, many times we have considered temozolomide-based therapy in those patients in efforts to shrink that cancer and then have it removed potentially for curative intent. There certainly is a role for neoadjuvant therapy, but it’s a little bit more limited in our disease.

Having said that, an approach of not jumping into surgery, before doing so even with the test of time, is often something that more we do frequently. For example, in our disease, you may have what looks like an isolated liver metastasis. But what if, for example, it may require right hepatectomy, which is a big deal for our patients? Do you want to jump in and do that? Or maybe it’s more of an intermediate grade tumor where we want to “reset the clock” but maybe the biology just won’t let us do that. The test of time in a neoadjuvant approach may be very helpful for the patient, so that we’re not inappropriately jumping into surgery and potentially hurting the patient.

Matthew H. Kulke, MD: You mentioned embolization, and one really tough question that comes up a lot is when you have a patient with three, four liver metastases, should they be embolized or should they get debulking surgery? Eric, you want to start off with that?

Eric H. Liu, MD, FACS: Yeah. I actually have pretty strong feelings about that, because with the embolization techniques we have now, maybe in a setting of an aggressive type of adenocarcinoma, they may not survive long enough to see the long-term consequences. We’re talking about radioembolization, bland embolization, chemoembolization, your choice. Since our patients live for a long time, we can actually see these long-term sequalae, so it is something to think about. You want to make sure you choose the right therapy. If you’re taking three or four tumors, which are maybe possibly well behaved, maybe you don’t want to subject the liver to all that.

The good thing is that surgery is still a very effective therapy. If they’re round, discrete, they can either be enucleated or just wedged out. It can be done very, very safely with our new therapies. But if it tends to be a little more military—4 lesions, 25 lesions—I can remove them, but 1000 lesions I can’t remove. That may be a more useful setting for a more diffuse type of therapy like embolization.

Diane Reidy Lagunes, MD: I agree that radioembolization for our disease, I get a little worried about using, because we don’t know the long-term effects We’ve used bland embolization for a couple of decades, and in the setting of progressive disease, the benefit is that you are treating the whole liver. I think most of us recognize that when you’re really removing those three to four tumors, we know that there’s more there. So it is absolutely not curative. Can you avoid maybe or can you allow yourself to reset the clock by doing that?

Maybe, but that is why it’s so important to go to these big centers or have these multidisciplinary teams to better define each patient because everyone is so different. If I may add, too, part of that importance is really having good imaging. Everyone relies on CT scans, and it’s great and well proven, and you can do it quickly and relatively inexpensively, but there are certain technologies which are more sensitive for liver lesions, say an MRI with diffusion weighted. And this new imaging technology, which is coming soon hopefully, this gallium technology, may pick up lesions maybe not even in the liver but maybe just a bone metastases. Maybe I don’t necessarily want to do a Whipple in someone if they have multiple bone metastases, so it’s just something to consider. Part of that individualization, those criteria, is having good data and good information to start with.

Transcript Edited for Clarity
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