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Recommendations for Resectability in Melanoma

Panelists: Jeffrey S. Weber, MD, PhD, NYU Langone Medical Center; Robert H. I. Andtbacka, MD, CM, Huntsman Cancer Institute; Georgina Long, MD, PhD, Melanoma Institute of Australia at the University of Sydney; Michael A. Davies, MD, PhD, University of Texas MD Anderson Cancer Center; Jason J. Luke, MD, University of Chicago
Published: Wednesday, Jul 05, 2017



Transcript:

Jeffrey S. Weber, MD, PhD:
Hello, and thank you for joining us today for this OncLive Peer Exchange panel discussion on the management of advanced melanoma. We continue to generate exciting data in the field of melanoma that include achieving long-term survival like we haven’t seen before. Today I am joined by a group of renowned experts in the field who are working hard every day to find answers to the most important questions we face in the field, such as, how do I help the next patient who comes into my office to live a longer life while making sure that the therapies that I treat them with are not worse than the disease? In this OncLive Peer Exchange discussion, we’ll provide perspective on the latest research and share practical advice that applies to the clinic.

My name is Dr. Jeffrey Weber, and I’m the deputy director of the Laura and Isaac Perlmutter Cancer Center and professor of medicine at the NYU Langone Medical Center in New York City. Joining our distinguished panel to share their perspectives are Dr. Robert Andtbacka, who’s an associate professor in the Department of Surgery at the University of Utah and co-director of the Melanoma Clinical Research Program at the Huntsman Cancer Institute in Salt Lake City, Utah; Dr. Michael Davies, who is an associate professor and deputy chair of the Department of Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas; Dr. Georgina Long, who’s a professor of melanoma medical oncology and translational research at the Melanoma Institute of Australia at the University of Sydney in Sydney, Australia; and Dr. Jason Luke, who is an assistant professor of medicine at the University of Chicago in Chicago, Illinois. Thank you again for joining us. Let’s begin.

We’re going to start by thinking about melanoma—locoregional, adjuvant, advanced, metastatic—and then we’ll talk about new drugs. I’d like to start talking about an issue that came up at the oral melanoma session here at ASCO, where we talked about the definition of resectability. So, Robert, what are the criteria for deciding if a patient with melanoma is resectable? How do you think about that?

Robert H. I. Andtbacka, MD, CM: It’s actually a very difficult question to answer, Jeffrey. I think that their resectability really depends on who is looking at it. It’s really in the eye of the beholder. For me, as a surgical oncologist, I really look at the usefulness of surgical resection. If I do this surgical resection, is that going to be a meaningful resection for the patient in its ability to cure the patient of their disease? For instance, in patients who have in-transit disease—if they have a few small in-transit lesions—we would consider that to be surgically resectable. However, many of our patients may have a large group of in-transit lesions, and although we could surgically take them out, it really would not be a meaningful surgical resection, because the risk of recurrence is so high outside of that surgical field.

The same thing applies to patients with metastatic lymph nodes. So, if the patient has a small amount of disease that we found on a sentinel lymph node biopsy, we would then recommend taking out the rest of the lymph nodes. However, in patients who have large, bulky disease, we often consider them for surgical resection, but the challenge there is that for many of them—although we can surgically take the lymph nodes out—the risk of locoregional recurrence is very high. So, features that clearly make something unresectable from a lymph node perspective are if you have involvement of vessels or involvement of nerves, where you would have to take out vessels and nerves, as well. In that situation, although we could surgically take it out, I don’t think that that’s a meaningful surgical resection for the patient. However, for patients who have 1 lymph node with metastatic disease, we can often surgically resect that.

Jeffrey S. Weber, MD, PhD: Another issue that certainly arises at my institution, and probably at all of your institutions, is, what do you do when a patient has a sentinel lymph node biopsy and has a positive sentinel node? Do you always do a completion lymphadenectomy? Robert, why don’t we start with you, but we should solicit some other opinions. I’m very curious about how it goes at other institutions. What are the criteria for completion lymphadenectomy?

Robert H. I. Andtbacka, MD, CM: I think, until recently, we would recommend everyone to go to a completion lymph node dissection for several reasons. We know that patients have between an 8% and 50% risk of having additional lymph nodes with melanoma in that lymph node basin. What is challenging is trying to determine who are the patients who will actually have additional disease, and there are a number of studies, mostly retrospective studies, that have been conducted to try to determine that. We know that features such as the Breslow thickness of the primary tumor, the amount of melanoma in that sentinel lymph node, and the number of sentinel lymph nodes that are removed influence this. In other words, if you have a thicker tumor, if you have more disease in the sentinel lymph node, and if you have 1 versus 3 sentinel lymph nodes being removed, the risk is higher.

Now, I think the landscape is changing, and we had the DeCOG study that came out from Germany, where they followed patients with an ultrasound versus doing a completion lymph node dissection. One of the challenges with that study is that they wanted to have about 1200 patients enrolled, but they only had around 400 patients in the study, so I think that it did not meet accrual. In that study, though, we know that the local recurrence rate was higher if you didn’t do a completion lymph node dissection, but it does not seem to affect the risk of distant metastases-free survival or potentially the overall survival for the patient. The MSLT-2 study, which is a much larger study that was done internationally, will be coming out shortly.

Jeffrey S. Weber, MD, PhD: When will we know those results? Because the MSLT-2 study seems critical to how we manage the patient.

Robert H. I. Andtbacka, MD, CM: We will know those results on June 8, 2017, in the New England Journal of Medicine.

Jeffrey S. Weber, MD, PhD: Fantastic. It sounds like you already know the data.

Robert H. I. Andtbacka, MD, CM: I do know the data, but they are embargoed, so I can’t reveal all of that. But what I can say is that I think the landscape will change, and it already has changed in many cases across the United States. In many institutions, they no longer do a completion lymph node dissection. Having said that, I think we have to be careful. I think that there clearly are patients who have a large amount of tumor in those sentinel lymph nodes, and the risk of having additional disease is very high. If they have a recurrence, that recurrence can become quite difficult to treat locally. In addition, I think we have to remember that every adjuvant trial we’ve had so far for patients with metastatic melanoma has required a completion lymph node dissection. So, we truly don’t know the use of adjuvant therapy in patients who have not had a completion lymph node dissection.

Jeffrey S. Weber, MD, PhD: Right. That’s a very good point. Georgina, you work in a classically multidisciplinary clinic with some very impressive surgeons. So, do all patients with a positive sentinel node at the Melanoma Institute of Australia get a completion lymphadenectomy, or do you pick and choose who to have the surgeons operate on?

Georgina Long, MD, PhD: Our surgeons are very much like what Robert said. Classically, we would recommend a completion lymph node dissection, if at sentinel node biopsy there was melanoma involved in that node. However, just as Robert said, things are evolving and changing right now, particularly with the MSLT-2 study results, and it will now be a discussion with the patient in terms of risk of further lymph node involvement. Also, recurrence in a local site, although it may not be the cause of death, is pretty morbid; therefore, it will be all about the risk of further lymph node involvement and the volume at sentinel node biopsy that will determine the viability of completion lymph node dissection. But at this point, until the data are widely available and known, yes, we would normally recommend a completion of lymph node dissection after discussion with the patient about the risk of lymphedema and the proposed benefits of the surgery.

Jeffrey S. Weber, MD, PhD: Yes, so not only the results of MSLT-2 but also the fact that now-emerging adjuvant therapies seem very effective at prolonging survival may change that.

Transcript Edited for Clarity

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Transcript:

Jeffrey S. Weber, MD, PhD:
Hello, and thank you for joining us today for this OncLive Peer Exchange panel discussion on the management of advanced melanoma. We continue to generate exciting data in the field of melanoma that include achieving long-term survival like we haven’t seen before. Today I am joined by a group of renowned experts in the field who are working hard every day to find answers to the most important questions we face in the field, such as, how do I help the next patient who comes into my office to live a longer life while making sure that the therapies that I treat them with are not worse than the disease? In this OncLive Peer Exchange discussion, we’ll provide perspective on the latest research and share practical advice that applies to the clinic.

My name is Dr. Jeffrey Weber, and I’m the deputy director of the Laura and Isaac Perlmutter Cancer Center and professor of medicine at the NYU Langone Medical Center in New York City. Joining our distinguished panel to share their perspectives are Dr. Robert Andtbacka, who’s an associate professor in the Department of Surgery at the University of Utah and co-director of the Melanoma Clinical Research Program at the Huntsman Cancer Institute in Salt Lake City, Utah; Dr. Michael Davies, who is an associate professor and deputy chair of the Department of Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas; Dr. Georgina Long, who’s a professor of melanoma medical oncology and translational research at the Melanoma Institute of Australia at the University of Sydney in Sydney, Australia; and Dr. Jason Luke, who is an assistant professor of medicine at the University of Chicago in Chicago, Illinois. Thank you again for joining us. Let’s begin.

We’re going to start by thinking about melanoma—locoregional, adjuvant, advanced, metastatic—and then we’ll talk about new drugs. I’d like to start talking about an issue that came up at the oral melanoma session here at ASCO, where we talked about the definition of resectability. So, Robert, what are the criteria for deciding if a patient with melanoma is resectable? How do you think about that?

Robert H. I. Andtbacka, MD, CM: It’s actually a very difficult question to answer, Jeffrey. I think that their resectability really depends on who is looking at it. It’s really in the eye of the beholder. For me, as a surgical oncologist, I really look at the usefulness of surgical resection. If I do this surgical resection, is that going to be a meaningful resection for the patient in its ability to cure the patient of their disease? For instance, in patients who have in-transit disease—if they have a few small in-transit lesions—we would consider that to be surgically resectable. However, many of our patients may have a large group of in-transit lesions, and although we could surgically take them out, it really would not be a meaningful surgical resection, because the risk of recurrence is so high outside of that surgical field.

The same thing applies to patients with metastatic lymph nodes. So, if the patient has a small amount of disease that we found on a sentinel lymph node biopsy, we would then recommend taking out the rest of the lymph nodes. However, in patients who have large, bulky disease, we often consider them for surgical resection, but the challenge there is that for many of them—although we can surgically take the lymph nodes out—the risk of locoregional recurrence is very high. So, features that clearly make something unresectable from a lymph node perspective are if you have involvement of vessels or involvement of nerves, where you would have to take out vessels and nerves, as well. In that situation, although we could surgically take it out, I don’t think that that’s a meaningful surgical resection for the patient. However, for patients who have 1 lymph node with metastatic disease, we can often surgically resect that.

Jeffrey S. Weber, MD, PhD: Another issue that certainly arises at my institution, and probably at all of your institutions, is, what do you do when a patient has a sentinel lymph node biopsy and has a positive sentinel node? Do you always do a completion lymphadenectomy? Robert, why don’t we start with you, but we should solicit some other opinions. I’m very curious about how it goes at other institutions. What are the criteria for completion lymphadenectomy?

Robert H. I. Andtbacka, MD, CM: I think, until recently, we would recommend everyone to go to a completion lymph node dissection for several reasons. We know that patients have between an 8% and 50% risk of having additional lymph nodes with melanoma in that lymph node basin. What is challenging is trying to determine who are the patients who will actually have additional disease, and there are a number of studies, mostly retrospective studies, that have been conducted to try to determine that. We know that features such as the Breslow thickness of the primary tumor, the amount of melanoma in that sentinel lymph node, and the number of sentinel lymph nodes that are removed influence this. In other words, if you have a thicker tumor, if you have more disease in the sentinel lymph node, and if you have 1 versus 3 sentinel lymph nodes being removed, the risk is higher.

Now, I think the landscape is changing, and we had the DeCOG study that came out from Germany, where they followed patients with an ultrasound versus doing a completion lymph node dissection. One of the challenges with that study is that they wanted to have about 1200 patients enrolled, but they only had around 400 patients in the study, so I think that it did not meet accrual. In that study, though, we know that the local recurrence rate was higher if you didn’t do a completion lymph node dissection, but it does not seem to affect the risk of distant metastases-free survival or potentially the overall survival for the patient. The MSLT-2 study, which is a much larger study that was done internationally, will be coming out shortly.

Jeffrey S. Weber, MD, PhD: When will we know those results? Because the MSLT-2 study seems critical to how we manage the patient.

Robert H. I. Andtbacka, MD, CM: We will know those results on June 8, 2017, in the New England Journal of Medicine.

Jeffrey S. Weber, MD, PhD: Fantastic. It sounds like you already know the data.

Robert H. I. Andtbacka, MD, CM: I do know the data, but they are embargoed, so I can’t reveal all of that. But what I can say is that I think the landscape will change, and it already has changed in many cases across the United States. In many institutions, they no longer do a completion lymph node dissection. Having said that, I think we have to be careful. I think that there clearly are patients who have a large amount of tumor in those sentinel lymph nodes, and the risk of having additional disease is very high. If they have a recurrence, that recurrence can become quite difficult to treat locally. In addition, I think we have to remember that every adjuvant trial we’ve had so far for patients with metastatic melanoma has required a completion lymph node dissection. So, we truly don’t know the use of adjuvant therapy in patients who have not had a completion lymph node dissection.

Jeffrey S. Weber, MD, PhD: Right. That’s a very good point. Georgina, you work in a classically multidisciplinary clinic with some very impressive surgeons. So, do all patients with a positive sentinel node at the Melanoma Institute of Australia get a completion lymphadenectomy, or do you pick and choose who to have the surgeons operate on?

Georgina Long, MD, PhD: Our surgeons are very much like what Robert said. Classically, we would recommend a completion lymph node dissection, if at sentinel node biopsy there was melanoma involved in that node. However, just as Robert said, things are evolving and changing right now, particularly with the MSLT-2 study results, and it will now be a discussion with the patient in terms of risk of further lymph node involvement. Also, recurrence in a local site, although it may not be the cause of death, is pretty morbid; therefore, it will be all about the risk of further lymph node involvement and the volume at sentinel node biopsy that will determine the viability of completion lymph node dissection. But at this point, until the data are widely available and known, yes, we would normally recommend a completion of lymph node dissection after discussion with the patient about the risk of lymphedema and the proposed benefits of the surgery.

Jeffrey S. Weber, MD, PhD: Yes, so not only the results of MSLT-2 but also the fact that now-emerging adjuvant therapies seem very effective at prolonging survival may change that.

Transcript Edited for Clarity
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