Raja Flores, MD, Chief of Thoracic Surgery at the Icahn School of Medicine at Mount Sinai, speaks with CTSNet Editor-in-Chief Joel Dunning about new guidelines and shifting standards in lung cancer surgery. Dr. Flores emphasizes the importance of managing the influx of data from lung cancer clinical trials and evaluating recommendations in the context of nuanced, personalized approaches for optimal outcomes. Their discussion took place at the 2024 Annual Meeting of the Society of Thoracic Surgeons.
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Credit: CTSNet is jointly overseen by The Society of Thoracic Surgeons (STS), the American Association for Thoracic Surgery (AATS), and the European Association for Cardio-thoracic Surgery (EACTS).
Hello, my name is Joel Dunning and we're here at Sts 2024 in beautiful San Antonio with an absolute hero of mine. Uh Rager Flores from the Mount Sinai Hospital, always such a wonderful eloquent speaker. Uh and uh no exception here at Sts. And uh so I want to talk to, I literally want to talk to you for two hours about everything because you always teach me so much. But uh but, but one thing that you will be doing very soon is you've got a little debate uh with Frank Debeck and uh maybe you want to tell us a little bit about the topic and uh and, and what you're going to be saying uh all about this subject. So it's, it's an interesting debate because it's very practical. You know, the committee on Cancer, the Commission on Cancer in the United States version 5.8 is recommending that every patient have three mediastinal nodes and one higher node dissected every patient without fail. And, you know, whenever you're taking a multiple choice test, when they say always, that's probably not the answer. And so, you know, we're gonna have a lively debate and I'm excited, you know, Frank Detter Beck, when I was a resident in the nineties, I read all of his stuff. So he basically a lot of his ideas, I've internalized. So I, I couldn't be happier than to debate someone who I've looked up to for so long. So I guess, I guess the logic might be to try and encourage good lymphadenectomy. Uh, but I guess, uh, your point would be that this misses the point of being nuanced for the the patient in front of you, would you say? And that's the thing, it's very nuanced. You know, now, in this age of personalized medicine, you need to tailor the treatment to the person that's in front of you. So just to say that every single lung cancer patients needs three mediastinal nodes and a higher node at surgery, I just, I can't, I can't swallow that. And especially nowadays as our field has evolved where we have gone from doing radical lobectomies, which is a lobectomy with nodal dissection which originated at Memorial in 1960 by Doctor Khan. Um Now with Nasser Al Turkey's randomized trial where wedge is OK, things have shifted and we need to shift along with it. You know, nowadays, we get so excited about immunotherapy about targeted therapy. And we wanna tailor that to the patient if they have PDF one or if they have EGFR et cetera. So I don't think cancer should be any different when we approach it from a surgical viewpoint because nowadays, because of screening, we are seeing patients with part solid nodules GG OS. We, we're seeing patients with cancers that just don't go to the lymph nodes for more advanced. I'm all for it. Let's take out every single node and it belongs in the pot. But these early stage cancers, where should we even be operating on them or not? Or should we just be uh uh observing them to say, to go in there and get lymph nodes from all over the chest? I don't know if that makes sense to me. Yeah. And that's, there's so many really important and relevant points and maybe just the question about the K GB trial, how has that changed your practice? Has that allowed you to feel that you can do a smaller procedure and go earlier in there? I, I often regard it sometimes with just going in there diagnostically to find out what is this GGO? And uh so how has that changed your practice? It really hasn't, not because it's not an important study, but because we figured that out before the results. So we were already doing segmentectomy and wed resections for specific types of lung cancers before the CAL GB trial came out. So I think it's a very important trial and I think it's gonna help a lot of surgeons their practice, but we were already practicing like that before the results. So you're doing a talk about N two nodes and N one node. So the million dollar question you're doing a segmentectomy. What about those N one nodes? Do you send them a frozen? Do you worry about them if they're positive? Do you go back? What's your policy? I mean, those are all good questions. It depends on what is the lesion that you're taking out. So let's say you are taking out a lesion, a solid lesion, you're doing a segmentectomy and you take out that node and you send it for frozen and it comes back as positive. Do you complete the lobectomy? Is that enough? And there's gonna be some other abstracts at that setting that talk about that. And I think we still need more data to determine it when you look at the J Cog trial, the Japanese trial that showed segmentectomy versus lobectomy. They went ahead and did the lobectomy when they had positively inner lobar lymph nodes. That is our philosophy now. But with time and more data, will we say? OK, segmentectomy is OK. Even if the nodes, even if the nodes are positive, as long as you get rid of all of them, will that actually change survival? Uh I I It's, I'm trying to put myself on the table if I had a segmentectomy and those nodes are positive, would I be happy not having a lobectomy? And it, I think I'd want the lobectomy. Uh But that's my bias. And I think a lot of the data is going against that. I think a lot of the data is showing you don't need to complete the lobectomy. But, you know, it's very hard to change what you've been raised with. Absolutely. And if, uh, and I guess in America, you know, if we go to the much more severe end, you know, the N two or even N three patients, you, there's so much, uh, chemo io and uh uh new adjuvant treatments and uh you know, how has your practice changed in the last sort of three years uh with this avalanche? And, and how do you keep your head around it all, it is tough to really get your arms around all the new data coming out. And I think as surgeons, we have to be very skeptic skeptical about what we're reading almost every single trial, induction trial that you see. They say there's no difference in surgical resection between the two arms. Meaning, you know, you have the neoadjuvant arm with uh induction thera uh induction immunotherapy and the chemo arm with induction chemo. No difference between the two arms, but induction chemo is not the standard. And when you look at both arms, sure, they equally go to surgery. But when you look in the supplement section of these papers, you'll note from study to study, to study agent checkmate uh Heather Wakeley, study all these studies, 20% in both arms don't make it to surgery and another 20% have delayed surgery. So 40% have their surgery affected by the neoadjuvant component. So I'm not jumping on that bandwagon as quickly as I think everybody else is. And we recently have uh new data coming out of our institution that when you delay surgery by 2 to 3 months, depending on the type of tumor, you have fast growing, medium growing and slow growing with a fast growing tumor. If you delay that surgery by 23 months, you can potentially affect five year survival by as much as 8%. So we need to make sure that if we're given induction chemo that the benefit we are getting of that induction chemo outweighs the potential downside of delaying or not even going to surgery. And, and I just don't see anyone bringing up that conversation. You know, many times we take these randomized controlled trials and say, ok, that's it. This is law and I disagree. I think actually for surgical practices, I'm and I, I have a master's in biostatistics and clinical research methods. All that stuff. I, I just don't know if I buy that randomized controlled trials are gonna answer the question for many of the things that we practice on today. And I like a Z 30 randomized control trial. No difference between nodes and sampling. We kind of knew that Nasser's trial, Lobectomy versus sub lobar resection. We kind of knew that Mars, I don't know if we're gonna be able to answer the meso question with a randomized control trial. There are other ways to do this and we don't always need a randomized controlled trial to make common sense out of things. Now, I'll tell you there is a Yankee Yogi Berra who said common sense ain't too common. So I do think we need these studies to go ahead and answer these questions. Uh But in general, most of it, I think we can figure out. Yeah, I mean, to your point, a lot of these are drug company sponsored trials and they take a huge wild group of patients and uh perhaps the more the, the three A Ns and the three BNS are dragging the differences whereas, you know, your stage two person or you're bigger than four centimeters, stage one patient, you know, maybe they don't need uh this treatment. Uh I, I agree, I think there, there's a lot of questions but these randomized trials that we're embarking on aren't necessarily answering them and they're actually generating more questions than answers. So I am curious to see which direction the field goes. Uh But uh I'm concerned that many people are jumping on this bandwagon without enough evidence to support it. I guess at the Sts just now, we just heard the President's speech talking about the Amazing Sts Database linking it to long term survival and readmissions in hospital. Do you think instead of these randomized trials, we should maybe be looking to, to huge database studies. Uh or do you think they can't keep up with the uh changes in the ment treatment? Well, I think it's very important to understand just like everyone knows garbage in means garbage out. So your data is only as good as the quality of the data that you record at our institution. Now, we have something called Il Cart, which is the International Lung Cancer Action Project treatment. So Il Cap is the group that knew ahead of time that lung cancer screening worked. The NLST trial was put together to prove Il Cap wrong. So of course, I'm biased. This is at our, at our institution at Mount Sinai in New York City, Claudia, Henske, David Dan Kit. So in 2006, they came up with their study that was published in the New England Journal of Medicine that said screening works ct screen and then Il Cap came out in 2011. It was supposed to say that it didn't work, but it did the opposite and it showed it did work. So we took that methodology and we created something called Il Cart, which we are looking at surgical questions on the same methodology that figured out that lung cancer screening worked without having to do a randomized control trial. And so all of that is in place at our institution. And um I just think that may be a better way than these expensive randomized trials and then the the data is obsolete with this. It's a continuous prospective gathering of data with specific questions in mind at the beginning. So over the next 20 years, we know what we wanna look at. And so as things advance pet scan, newer techniques that's incorporated, so, you know, with some of these randomized trials, let's say ACUs Z 30 there's no pet scan, you know, so you need to be able to look at these trials as they are developing. Yeah, that's a really fascinating uh approach. And, and, and I guess mentioned very briefly was the Mars two trial again, another example of a randomized trial. Uh, that's, and you're obviously an absolute expert in mesothelioma surgery. You know, um, how has that impacted your practice? What were the weaknesses of that? And could this new methodology you discuss, you know, could that be a better solution for the mesothelioma where we go next? I think mesothelioma is a very difficult disease to get your arms around. Is it a surgical disease? Is it not a surgical disease? It's been a surgical disease since the 19 thirties. Have we been wrong all this time? I don't know. Of course, I'm biased. I operate on mesothelioma and it's funny because some people were saying, well, you're going against going after lymph nodes, but you operate on mesothelioma. Yes, there is contradiction in everything we do. And I think that with specifically the Mars two trial, there were just so many flaws. The operative mortality approaching 9% 15% had non epithelioid tumors. They operated on 4% who had M one disease. There, there were just many different flaws. And then when I looked at the statistics of the study, it looked like they were doing statistical gymnastics. You know, they, you know, there's a saying that when the study works, you have your P value of, you know, less than 0.05 et cetera. When that P value starts going higher and higher, look at this great subset analysis, you know. So I, I think there is, I think it was a valiant effort. I think we need more surgeons involved in clinical trials, but we also need to make sure that it is reflective of real life. And I don't think the Mars trial in its haste for completion uh is what, how we actually practice on measle patients. So I, I don't agree with their conclusions. Where do you think the future lies in Mima surgery? Would you say it is the database that you, you describe or, or where are we going would you say? Yeah, I think you need something like what we have I cart where we're trying to figure out these answers using very specific prospective data that's gathered by our researchers. But meso is you can do a lobectomy that's on you. On me. That's a lobectomy when you have measles, you know, it has a propensity to spread through the tissues and planes. No, two measles are the same. So it's very hard to have a control group and an experimental group. Um, and a lot of it and just like much of what we do in surgery is based on the patient in front of you and based on your own biases. So I'm biased as a meso surgeon. I think meso surgery works and I think it's something that really adds, uh, life years to the patient. But I know some medical oncologists don't buy it at all. They're like, no, you're gonna die as you're gonna live or die as long as you're gonna live or die with or without surgery. I understand where they're coming from. I've had some meso patients who refuse surgery who I just drained their refusion and they're alive 78 years later. But I also do have patients where I've done pleurectomy decorations, even extra plural pneumonectomy. And they're alive 1520 years later. Are they alive because of what I did? Or in spite of what I did, I don't know. But, you know, as a surgeon, when you're a hammer, the whole world's a nail. So you operate. Yeah, that's fantastic. And so what, what do you think perhaps in the lung cancer surgery? Where are we going in the next five years? Um, to me it seems an inexorable track into neoadjuvant treatments and, and then post uh surgery treatments. But, but if we're talking in, in 2028 in, in the sts in Mount Sinai. Maybe we can come to you. What do you think we'll be talking about? Well, I think in cancer surgery in general we're moving towards less surgery. Not more when you look at the radical mastectomy, right? You go now to lo lumpectomy and radiation when you talk about, you know, colon resection where we would, you know, uh or stomach resection with the D two nodal dissection. I think we're going to less surgery. Not more, you know, we went from pneumonectomy for lung cancer to lobe to me to now less than a lobectomy wedge resection, segmentectomy. Same thing with mesothelioma. We went from extra pleural nect toy to pleurectomy, decortication. So, in every area of cancer, we are doing less and less surgery. And that's why I think this nodal discussion that, that we're gonna have is, is an important one because it's do we do more nodes or do we do less nodes and it depends on the tumor. I mean, when I have more advanced cancers, I mean, I will take every single note that's in that area. But do we need to do that for these little guys? I don't know. So, uh I think thoracic surgery along with cancer surgery is evolving to the point of being smaller, less invasive, better operative outcomes. I mean, when you look at uh CALG the CAL GB trial, the mortality rate was extremely low. It was less than 1% in each arm. So, as we have advanced in time, our mortality rates for the surgeries we do are getting lower and lower. And it's really important because that means we can do older and frailer patients, isn't it at the end of the day? That's, and I think that's super important because so many people don't get treatment or the adequate treatment they should have because they're 85 or no. I completely agree. You know, you have to look at that individual. I just did an 83 year old with, with an esophageal, you know, so it's, I think that as we move forward, we just have to be sure that um just one size doesn't fit on. Yeah. Well, I'll be voting for you on your side. Uh So best of luck with that and it's so such a pleasure to talk to you as always. Uh And uh it's really great to see you. Thank you so much for coming to talk to us here. No, great to see you Joel. I'm gla, I'm glad you're heading CTS ned. I couldn't think of a better person. Now. You're so kind. Well, thanks a lot and hopefully we'll talk again very, very soon.
