Mediastinal Staging in Non–Small Cell Lung Cancer

Mark Socinski, MD: Hello and welcome to this OncLive Peer Exchange®: “Multidisciplinary Management of Locoregional Non–Small Cell Lung Cancer.”

I’m Dr Mark Socinski from the AdventHealth Cancer Institute in Orlando, Florida. Joining me today in this virtual discussion are my colleagues, Dr Roy Herbst, a medical oncologist from the Yale Cancer Center in New Haven, Connecticut; Dr Stephen Liu, a medical oncologist from the Georgetown Lombardi Comprehensive Cancer Center of Georgetown in Washington, D.C.; Dr Kristin Higgins, a radiation oncologist at the Winship Cancer Institute of Emory University in Atlanta, Georgia; and lastly, Dr Brendon Stiles, a thoracic surgeon from the Weill Cornell Medical Center in New York.

Today we’re going to discuss a number of topics pertaining to the use of systemic therapy in patients with stage I through III non–small cell lung cancer. We’ll discuss the latest research in the field, including new data from the ASCO [American Society of Clinical Oncology] 2020 virtual meeting and the impact of recent clinical trials on making decisions around treatment selection.

Let’s get started on our first topic. In this population of patients, staging is a cornerstone of making decisions about future therapies. I wanted to ask Brendon to give us his thoughts, particularly on something that I think historically in the United States is often a shortcut in the work-up of patients, and that’s the adequate evaluation of the mediastinum in defining pathologic involvement of mediastinal lymph nodes and the various techniques we have to do the mediastinoscopy versus EBUS [endobronchial ultrasound] and those sorts of things. Give us your perspective on that mediastinal staging. Who needs mediastinal staging, what's the best way to do it? What are the pitfalls of EBUS, what are the pitfalls of mediastinoscopy? Start us off there.

Brendon Stiles, MD: You raised some great points Mark. I think we’re all excited to see both targeted therapy and immunotherapy moving into earlier-stage disease. But as you allude to, staging obviously becomes critical there and the sequencing of therapy, whether we even choose to include surgery as part of the therapy or whether we go to definitive chemoradiation, staging is critical for both resectable and unresectable patients.

I think the key point is as you hinted, staging needs to be done, and it’s probably best not just done with a PET [positron emission tomography] scan, but by invasive mediastinal staging. This is generally a population that’s getting considered for these trials because they’re thought to have positive lymph nodes, either N1 or N2 nodes. We know that if they have N1 nodes, they might have N2 nodes; if they have N2 nodes, they might have N3 nodes. I think it’s inherent upon us to stage well and to stage multiple stations. I think that can be done well by lots of folks, whether it’s a thoracic surgeon or a skilled pulmonologist.

I see EBUS and mediastinoscopy largely as interchangeable. I think the key is doing something. Certainly, EBUS has gained favor, it’s easier on the patients, it doesn’t require an incision, and in many studies, its actually more accurate. I tend to believe that particularly when you’re looking for PET-positive nodes and going right to the nodes that you’re suspicious for, you can get there well with EBUS, you can do multiple samples, and the yield is very high. I think the one thing that’s interesting, where we’ve moved toward EBUS and largely away from mediastinoscopy, I think the incidental N-positive stuff, whether it’s incidental N2 or N3, we’re not probably finding as much. If you see a patient with bulky N2 disease, in the old days we’d stick a mediastinoscopy down, and by default you’d get some N3 from the other side just in small nodes.

With EBUS the tendency is a little bit more to guide yourself toward just the big nodes, and the smaller nodes that you think are perhaps not positive are a little bit more challenging. That can have some significant implications for the patients though, as from being IIIA to IIIB or IIIC. I’m in favor of making sure that we sample both sides, trying to narrow down the nodal involvement and to come up with an accurate stage.

Mark Socinski, MD: Then it’s just as important to do intraoperatively mediastinal staging. Could you comment on that?

Brendon Stiles, MD: That’s really key, and as we talk about adjuvant trials and I’m sure as Roy will talk about his trial, understanding which patients benefit is going to be key on doing good surgical staging during the operation. And there's a big difference between calling a patient stage I and taking 1 or 2 lymph nodes out, and calling a patient stage I and having sampled 31 nodes. Increasingly as we understand that we have agents that might be beneficial in the adjuvant setting, that idea of staging them well surgically, making sure that we get a lot of N1 nodes and N2 nodes so that we can be accurate there is critical, and probably has some implications for disease recurrence as well.

Mark Socinski, MD: Then this issue, the term is so cemented in our lung cancer culture, this term unresectable stage III. Does unresectable mean you can’t resect it, or does it mean you shouldn’t resect it? Give us your perspective on that.

Brendon Stiles, MD: I think the latter is true. I always say that resectability, like beauty, is in the eye of the beholder. I think that anything can be resected. The question is really should we resect it? We know that there's probably some that we shouldn’t, and I tend to think of that as bulky multistation N2 disease. Certainly, that’s going to act more the equivalent of systemic disease, but even more importantly, I pause when I know that I’m going to have to go down the pneumonectomy road with one of these patients with a high burden of disease. I think that inflicts almost a second disease upon patients, and I think it leads them down a long road where they're not going to tolerate systemic therapy and they're going to have a harder time on any of these trials that we’re talking about.

That said, have I done it and do I think it’s appropriate for some surgeons to do? Yes. In young patients with excellent performance status. In general, the data have suggested that pneumonectomy patients do worse.

If I can do a lobectomy, I might be a little bit more aggressive with a patient with multistation N2 disease. I think the real question is should it be resected? I think the challenge of that is that answer is probably different depending in where you are, your institution, your surgeon’s comfort levels.

Mark Socinski, MD: Let me ask Kristin. At least in my mind, this is an extension of it, obviously as you get to the perimeter of the surgical ability to resect something, you get into bulky disease. And volume in radiotherapy is so important, and we know that the toxicities are not necessarily related to radiating the cancer, it’s what the normal tissue around the cancer gets. What are your thoughts on radiation issues as they relate to tumor volume?

Kristin Higgins, MD: Stage III patients, the radiation technologies that we employ to treat these patients have evolved tremendously over the past couple of decades. In my mind, any stage III patient is treatable to a curative dose with radiation. We’re typically using IMRT [intensity-modulated radiation therapy] technique to treat patients who have bulky disease that have contralateral mediastinal nodes or mediastinal and hilar nodes, N3 nodes. But you can deliver 60 gray safely with these advanced technologies, and if you have dosimetrists and physicists experienced in planning radiation treatment plans for bulky disease, you can typically achieve your doses to your normal organs at risk such that you won’t hurt the patient. Part of that is expertise that you develop when you’re treating a high volume of patients with lung cancer. I think it could be delivered safely certainly also in community settings, and it's really changed what can be treated safely with radiation when it comes to stage III disease. I think almost every stage III patient can be treated safely with our latest and greatest technologies.

Transcript Edited for Clarity