The Mesothelioma Surgery Debate

One clinical trial can change an entire field overnight, and that’s exactly what happened after MARS 2. Suddenly, many pleural mesothelioma patients started hearing a blunt message: surgery is off the table. But when you zoom in, “surgery” is not one thing, and the difference between a lung-removing operation and a lung-sparing pleurectomy/decortication can be the difference between losing months to recovery and getting back to living.

We sit down with thoracic surgeon Dr. Jeff Vallada to unpack what MARS 2 actually tested, what it didn’t, and why the Society of Thoracic Surgeons released a 2026 multidisciplinary consensus that doesn’t match the simplest reading of the trial. We talk chemo-first versus surgery-first sequencing, why complication and mortality rates matter as much as survival curves, and how surgeon and center volume can quietly drive outcomes in complex mesothelioma surgery. If you’ve been told “quality of life” means “no surgery,” this conversation adds the missing context.

We also dig into how immunotherapy for mesothelioma, including ipilimumab plus nivolumab, changes the decision-making, especially for biphasic and sarcomatoid histology. Then we get practical about intraoperative add-ons like heated intrathoracic chemotherapy (HITHOC) versus lower-toxicity approaches, and we look ahead to vaccines, CAR T-cell therapy, PARP inhibitors, and other targeted treatments. Listen, share this with someone navigating mesothelioma care, and subscribe so you don’t miss the follow-up conversations. If this helped, leave a review and tell us what question you want answered next.

MESO: The Mesothelioma Podcast is sponsored by Danziger & De Llano, a nationwide mesothelioma law firm with over 30 years of experience and nearly $2 billion recovered for asbestos victims. For a free consultation, visit Dandell.com.

Transcript

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Welcome To Meso Support

SPEAKER_00 0:01

You're listening to Misto, the Mesothelioma podcast, where support, education, and outreach come together for families facing misothelioma.

SPEAKER_01 0:14

Hi guys, thank you for being here today. And um I am so grateful. I know um uh for each and every one of you uh to be here, uh, we have uh Ellie Eleanor Erickson, we call her Ellie. Um Lisa uh may pop in here in a few minutes, but as a special guest, we have uh Dr. Jeffrey Lovada. Is that correct? Yeah. Sorry. Jeff, Jeffrey, can you give me um well, we have a little bit of a background here.

SPEAKER_02 0:47

Did did you want to read through that, um, Dave, or do you want him to No, just love to you to give just a little bit of an intro on who you are and what you've done, although we talked about it before, we'd just love to quickly talk about what you've done and how you got here.

Meet A High Volume Meso Surgeon

SPEAKER_06 0:59

Yeah. Um, so thank you for having me on. And uh yeah, I'm Jeff Vallada. I am a thoracic surgeon uh at in the Kaiser Permanente Northern California system. Um but I also uh you know have you know kind of faculty positions at UCSF and the Kaiser Permanente School of Medicine. So I'm kind of a little bit of uh everywhere, a jack of all trades, I guess, a little bit. But in terms of mesothelioma, it's been an interest of mine since I left fellowship at the Brigham and Women's Hospital with David Sugarbaker in 2014. So from 2000, so I guess for the last 12 years now, um, been running a kind of regionalized centralized uh high-volume mesothelioma, uh, multidisciplinary team, uh, leading it from the surgical end, but obviously a multidisciplinary team with medical oncology, radiation oncology, uh, and thoracic surgery, kind of just seeing all of the mesothelioma cases uh in Northern California. And then um Kaiser is also in nine other states. Uh so we often uh do see a lot of referrals and a lot of uh virtual multidisciplinary tumor reports for uh mesothelium, for example, in Colorado. I've operated on Washington, Oregon, Hawaii, um, so you know, and and and obviously Southern California uh as well. So kind of seen it from uh a lot of different um different areas other than just uh Northern California. So happy to be on and kind of share any of my experiences.

SPEAKER_01 2:19

Oh, great. Thank you. So I I wanted to apologize ahead of time because um I I know I have Lisa Ellie and Dave, who is very well versed in medical terms, but I'm not. So a lot of the questions or what I'm going to be asking is probably more layman's than anything else. So um one of the things I did want to talk about, and Ellie had uh sent me some information about um Mars 2. But before we get into Mars two, I wanted to say, and and only because you know the clients or the patients that we talk to, um, you know, we hear the different things that are going on as far as treatments that they're going through. So if if you don't mind, I want to do this.

EPP Vs Lung Sparing Surgery

SPEAKER_01 3:04

So when we initially um, or when I initially came on with mesothelioma, the EPP was a big thing that if you qualified for it, you know, great, you're gonna have, you know, I even though it is a very um uh the recovery time is very, you know, it's it's it's it's very heavy, I guess. I don't know if that's the right word to say. The long road ahoe, that's for sure. But you know, we know quite a few people that have survived EPP, right? Um, and that was kind of a big thing at that time. And then um I guess there was a uh a paper written in 2024, Mars 2, 2024, where um they felt something different. They did a uh study um on those whether chemotherapy alone was the best thing for a client or chemotherapy followed by um EPD. And um the result of that was that they were kind of getting away from uh actually surgery, right? Um and so we would hear a lot of our clients say, yeah, they're not, they're you know, they're looking more at quality of life, they don't want to put us through all that. And then in 2026, tell me what happened.

SPEAKER_06 4:23

Got it. So that's a great, no, that's great. You did a great job of the great synopsis. But um what I would first say is regards to the extra pleural pneumonectomy, meaning where you take out the lining of the lung with the mesothelium, but also the lung versus the EPD, um, which the Mars 2 looked at, extended pleurectomy decortication, where you save the lung, lung sparing and just remove the lining. That the original Mars trial, so I guess you want to call it Mars 1 or Mars that came out, you know, uh over 10 years ago. Um, the interesting part of that that is that did show, again, that surgery again was not beneficial when it came to um surgery versus you know chemo uh chemotherapy. But that study, the reason why a lot of us didn't necessarily uh go off of that either was because that was what you alluded to earlier, which was that was comparing extrapleural pneumonectomy, EPP. And we know that that surgery, and we learned from that study that the surgery morbidity and mortality rates can be over 50%. Half the patients all develop complications. So, not surprisingly, a lot of them didn't make it that long. Um, but that again was based off of extrapleural pneumonectomy. So that led a lot of us after that study, even though extrapleural pneumectomy is still done, even today. In today, a lot of surgeons still do extrapleural pneumonectomies, believe it or not. And in fact, in Canada, it's fairly routine at some of these high volume places. Um but because of that, the majority of us, say 10, 12, 15 years ago or uh a little bit even longer ago, have really kind of shied away from extrapleural pneumonectomies. Um and and so um one of the interesting things that I got to experience, and I know uh Lisa's on and Ellie's on, is that um my time at the Brigham and Women's Hospital with Dr. Sugar Baker, uh, you know, before he moved to Houston, I was still there and he was still there uh up until 2014 as well as I was his last kind of chief resident, was that we saw that transition. So half of my cases during 2012 to 2014 were extra pleural pneumonectomies, and we were doing hundreds. Um, at Lisa Nelly remembered that. Um, it was back the old days where just everything came to us, and you know, three to four days a week we were doing mesothelium surgery, and half of those were done extrapleural pneumonectomy, the other half were done extra uh extended pleurectomy decortication or otherwise known as plectomine decortication. Um, and but I saw that over that time period, even in that two years, it's really fascinating, which is really why you know Dr. Schrickbaker is always kind of you know hard-nosed and everything. But he even began to um to understand the the the the some of the issues and the lesser comings of uh extra pleural pneumonectomy, where even during, I remember from 2012 to even later 2014, towards 2014 and 2014, we're almost always doing pleurectomy and decortication. So I really saw that differences. So and I really saw how patients recovered from extrapleur pneumectomies, which was tough and terrible, even at the best center in the world, um, versus pleurectomy and decortication, they were generally flying by and getting getting uh getting through. And and and even the Brigham published more that they had good data with pleurectomy decortication. So uh again, that's I saw that transition. So uh I guess we can pause there because I know it's being recorded or whatnot, but uh then I can go into the Mars two if you want to. But I just wanted to make that clear about the extra pleural.

SPEAKER_04 7:53

No, no, no, no, no. Perfect.

SPEAKER_06 7:55

Um okay.

MARS 2 And The Surgery Backlash

SPEAKER_06 7:56

Um so for Mars two, the big difference is that Mars 2 now compares surgery, but with all of the surgeries were pleurectomy decortication and or extended pleorectomy and decortication, but not extra pleurin pneumonectomy. And they were comparing that with chemo versus just chemo alone. And even in with just pleurectomy decortication, they again, similar to Mars 1, but you know, different type of surgery, they showed worsening survival in the surgery group, even though it was still a pleurectomy and decortication versus just the chemotherapy group. And so that's what Dr. Lim and colleagues at the United Kingdom published in 2024.

STS 2026 Guidelines Push Back

SPEAKER_06 8:37

However, fast forward to what you were talking about in 2026, uh I guess last month in July, we published out of the Society of Thoracic Surgery Guidelines a multidisciplinary group of 14 of us, thoracic surgeons, radiation oncologists, um, pathologists, and uh and radiation medical oncology, uh, a statement that looked at all the data, not just Mars 2, but looked at all the data and also was an expert panel of just kind of our own real world experiences that have been published, including the Brigham, including Memorial Stone Kettering, wherever you want to, all the you know, other University of Chicago, all the big places. Um, and we came together and looked at all the data in a systematic kind of review, formalized Delphi process voting, all these different things and discussions and over a year period. And we came up with more a combination of taking in the Mars 2 trial, but with all the other data, with all the other experience, the real world data and everything, and combining that and then coming up with our own kind of what we think of expert consensus documents, they're called, or guideline recommendations that you can use for your, you know, you know, patients that a surgeon in wherever Omaha can use, or a surgeon in Japan can use, or even the UK can look at uh and go, well, this is this group of 14 considered what we considered we rounded up an international world experts of the highest kind of experience with mesothelioma over 30 to 40 years. And, you know, we came up with kind of our uh recommendations that certainly be can go into, but definitely differed um than what we've seen in the Mars 2 trial.

SPEAKER_02 10:19

What was the uh shortcomings of the Mars 2 trial that were, you know, the US subjected to some of our Yeah.

Why MARS 2 May Mislead

SPEAKER_06 10:28

So I have a list of 10 things, but we don't have time for that. So um multiple people have different top three. Yeah, the top yes. The top three was one, uh, the the biggest issue was that a lot of us had was the trial design. We won't even get to the experience of the trial design. The trial design automatically required you to get chemotherapy first. Many of us in the United States don't even give chemotherapy first because there's been no trial. In fact, there was a recent trial, ERTC 1205, randomized controlled trial, that just showed that there was no benefit to giving it before and or after. It's the same, it's a dealer's choice. However, Mars 2, they, based on their, you know, what they were doing in the UK and in Europe, they decided both treatment arms were gonna get chemo first and then get surgery. But we know off of literature and data that only about 20 to 30 percent of all mesothelioma patients actually respond well to chemo. It is generally speaking, don't respond that well to chemo. And we know these patients are already sickened because they have potal fusions or they have, or they tend to be older or not as sick, and then you weaken them more with chemo, and then you do a big surgery on them. Uh, not surprisingly already, they are going to do worse compared to just getting chemo. Right, right. And so what a lot of us said that we want to do, and in fact, David Waller has told this to Joel Dunning, and David Waller was one of the authors and one of the main surgeons in the Mars 2 trial, uh, a prominent surgeon out of the UK wants to do Mars 3. And ideally, Mars 3, or what I will well, many of us in the United States would have liked to see a fair, fair comparison would have been you either get surgery followed by whatever chemotherapy, all your necks mix up first. So you're the strongest, that's when you can handle it, and then you give the chemotherapy, or you just give the chemotherapy and see. And I think a lot of us, which is what we do, a lot, many of us do, is uh, you know, often do surgery first, but we follow it up with chemotherapy, and that's what our guidelines really want. You need to get that systemic treatment in. But if you get the surgery in uh, you know, first, how would those patients do versus just getting chemo? Um, and a lot of us feel, and we've showed in uh again retrospective, so it's not a clinical trial, so it's uh, you know, but we've showed multiple studies, Mount Sinai, MD Anderson, uh, MSK here at Kaiser, uh, I'm forgetting some in Japan, uh, that the the again retrospective, not perfect, but patients that got surgery and systemic therapy versus just chemotherapy alone or even with immunotherapy alone, the group that got a multimodal approach with surgery and some type of systemic treatment lived much longer than the group that didn't. Um, and unfortunately, we don't have a randomized controlled trial looking at kind of apples, uh, you know, what we consider apples the apples and and whatnot. So trial design is was tough because a lot of those patients got weakened uh by chemotherapy um and didn't have a good response. And right away when you put them through a big operation after that, um you know, that's already is is an issue. That's number one. Um I know recorded, so I can it'll be like cut, right? Edit uh so number number number two, uh the you know, kind of the issue was was the uh extent of surgery complications was much higher. 30-day mortality, 30-day complication rate, and 90-day mortality were often three to four times higher than any other published big surgical literature with plurectamine decortication for mesothelioma. And for whatever reason, we don't really know. Um, right? It's just that's the data, right? But the re the mortality rates were three to four times higher, and 90-day mortality rate of 9%, meaning one in 10 of your patients were dead after surgery within three months. Okay, that is much higher than the other literature. Even within 30 days, their mortality rates of three to five percent were much higher with pleorectomy decortication, where many of authors um have shown that it's less than 1%. Uh, so already, if you have some of these patients dying off because of your surgical complications, your rate of survival will be lower because some more patients are dying earlier, then you're not gonna die right away from chemo. It's a slower death. We know that it doesn't, you know, and so the complication rates were really high. Now, not everybody knows why that is. One of the the the the qualms that some of us have, number three, was that the surgeons that were performing it considered high volume were usually only doing less than 10. Uh, many of us have done, you know, you know, hundreds or whatnot, or you know, 10, uh, you know, way more than 10 to 20 a year. So we in the expert group from the STS felt that just volume and experience with mesothelium was more important than anything. Um, and so we felt that the experience level of the surgeons performing, nothing against those surgeons, but certainly were high volume. They and those were considered high volume surgeons for this for the study, um, but were a lot less experienced, and that could have played a role in maybe some of the uh decision making in how to perform the surgery and what type of surgery and the complication rate. Number 3.5 also um was as you know essentially that the type of surgery we're performing. That's the thing where it gets complicated with mesothelioma. That's why it's hard to say that you should never do surgery. So we don't agree with that. There's all these different kinds. Even you brought it up, Anna, extended pleurectomine decortication. There's a regular pleurectamine decortication. There's uh some people call it a radical parietal and visceral plectomy. There's all these different kinds, right? You could go in and remove some of it, a lot of it, all of it, you can remove uh parts of the ribs, you can remove all of the diaphragm, only part of the diaphragm, you can remove parts of the pericardium, all the pericardium. You can reconstruct with different types of mesh. And the more, generally speaking, the more extensive, the more you take out. And in this case, you know, the majority of their cases were done, we're removing all the diaphragm and most of the pericardium. So uh where many of us in the United States, and this is where I learned from a lot of the other uh, you know, surgeons, especially out of Mount Sinai, that they haven't in six years they haven't taken out the diaphragm. 80 more than 80% were taking the diaphragm. We know that causes a lot of morbidity and mortality afterwards. And so it's not that those surges were wrong in the UK, but you know, it was it a lot of those surgeries were very, very big uh aggressive surgeries. And you can just it just makes sense, right? If the surgery, if you do better from surgery, or maybe it's done in a in a in a less aggressive way, but still get the same amount of cancer out and still get your macroscopic complete resection, um, because we know with mesothelioma, you can't remove all the tumor. You remove everything that you see, but you can't get rid of it. And that's why you give chemo. So just get them through an operation to live another day and they'll live longer and they'll have a better quality of life. And so again, um, a lot of those surgeries were a lot bigger surgeries and whatnot. So there's just so many nuances with this type of surgery that, yeah, I understand the data they found the survival was worse. But I kind of gave you a lot of the reasons why the survival is probably important. And can you extrapolate that for all the patients here in your in, you know, and in different ages and for 30-year-old woman that has this, can you extrapolate that and say that's dogma to not offer surgery anymore because of Mars 2? And all we're saying is that it's certainly reasonable to go by Mars 2 and if you want, okay, don't have to offer it. But there's many of us that have experienced mesothelioma that that you know think otherwise and have good anecdotal and published data to show that that is not true what we see with um uh Mars 2, even though that was a randomized controlled trial because of some of the the issues that I talked about before.

SPEAKER_02 18:15

At at every IMEG meeting I've gone to since uh the one that was held in Boston, there's been this big fight, right, about Mars 2 and Sugar Baker's name's always brought into that. And uh and in even in uh Philadelphia this year, right? Friedberg got up and was you know defending Sugar Baker's um you know legacy or whatever. But but if you just think about what you just said, the the 3.5 issues that you brought up, one probably contributed to two, uh, you know, the the mortality, right? The uh doing the chemo first probably did. So uh it's interesting. I I that was great, great information. Thank you so much. It's the best explanation I've heard so far. I'm glad Waller or none of these guys are in the room that can start debating with you about it.

SPEAKER_06 19:00

So well, that debate to be determined. That's it. I am debating, uh I don't know if I told you guys, but you can well gonna publish it because it'll be uh in Korea at World Conference Lung Cancer. Uh we are debating uh whether or not surgery should be done. And I uh so I'm debating that pro for surgery, a role for surgery. And this is in September 12th in Korea, the World Lung Uh Conference. But Eric Lim, uh, as the the lead author is the is the uh the the con of surgery should not be done. Um and I'm running that session, so that's why I invited him, but I'm glad he accepted. So I'm putting myself in the case.

SPEAKER_02 19:36

They get a little testy about it, right? So yeah, yeah.

SPEAKER_06 19:38

Eric, Eric Lim, because he's actually given a talk. I mean, he's the expert in this, right? He did the trial, plus he's given millions of talks worldwide about this. Um, and he is a purist. He is very much a randomized controlled trial, is the way to go. And I don't care what your experiences is, this is a randomized controlled trial of this versus this, and it was randomized and blinded, and and and nobody, you know, and so and that's what the level one evidence is. So um, you know, it'd be interesting. You're right. Uh, I'm definitely not thinking it's gonna be uh that that it that I'm gonna win and convincing. And I'm not trying to win, but we're making it fun by a pro con debate. Um, but he is very when he speaks, and I've seen a couple of his talks, he's he's he's he he can be very influential. Um convincing, yeah. Convincing, that's an even better term. Yeah, yeah, yeah.

Immunotherapy Changes The Math

SPEAKER_02 20:23

So well, if they did do a Marsh III, you'd have to throw in immunotherapy too. So that'll um make everything very complicated as well, right?

SPEAKER_06 20:30

Exactly. Exactly. That's the thing, is that you know, a lot of the treatment the and I love randomized controlled trials, but as you know from survival data and just setting it up and everything, when they set it up, it takes 10 years. So they set this up 10 years ago to run through all that data is just with chemo and and and old school surgery, you know? Uh the field's just too rapidly moving. Uh and yeah, of course, it finally, you know, trialed out and you saw the results, but that was done in an era that we don't even do that type of surgery as much anymore. And we use, like you said, the immunotherapy is game changing. Um, and and it's just it's just not relevant anymore. It's not apples to apples uh more because we know they're gonna recur. We're not saying your patients that see you, or I'm not telling my patients that we're gonna get rid of it forever and it's never coming back. We tell you you're gonna live with it. It's sucked and you have to live with, and you will need other treatments, but you can live with it. And if you can have a defense quality of life, you no longer, it's a no longer a death sentence within a year or two. Um, and that you can live longer uh with all of these new treatments. And uh, you know, you saw there's more treatments that are coming down the pike that are not just immunotherapy, that are actually related and treat well with mesothelioma. And so, um, you know, it's just that's the whole you right and brought up a great point, David, that the you know, they don't even take that into context, right? Because um, it was all done in trial before immunotherapy came on. But when immunotherapy came on several years ago for mesothelioma, not just for lung cancer, but for actual mesothelioma, it being Evo, I mean, it was groundbreaking, right? So I Yeah.

SPEAKER_02 22:02

Um, so and I don't mean to dominate here, epithelioid versus sarcomatoid.

Who Should Still Get Surgery

SPEAKER_02 22:07

Before immunotherapy, you didn't do much surgery on a sarcomatoid or biphasic, right? Now are you seeing, are you doing surgeries, or are you still kind of just letting immunotherapy do its thing?

SPEAKER_06 22:18

That so actually, so actually, great point. But I would say before that was one of the things uh that Mars 2 and so before immunotherapy and before Mars 2, I would say that one of the things we learned from Mars 2, and just what we learned anecdotally is that we were too aggressive. Many of us were too aggressive with biphasic and even sarcomatoid. Sarcomatoid was always classically considered non-operative because they just it comes back with so quickly and it's so aggressive, you die regardless. So most of us would say no, sarcomatoid, even before Mars two and after, right? But many of us were still doing biphasic. And in fact, the NCCN guidelines were taught, you know, before Mars II had biphasic in there. Biphasic andor epithelium. So I would say before Mars II, we were much more aggressive about, yeah, epithelial. Um, sure, but if it's biphasic, yeah, we'll do it. Um, and and but what Mars two taught us, and we definitely saw that, is the biphasics definitely did worse, and that was part of the problem, right? They included the biphasics in there, and that was part of what was bringing the survival uh, you know, uh, you know, shifts down because those that's just aggressive biology. They recur a lot quicker, even if you take it out, they just kind of come back. And so what many of us learn now, and especially with because you have Ipinevo and the checkmate trial showing that ipinevo does very, very well in patients that were considered unresectable, um, that especially for bi and had a pre-inkling for better doing better with biphasic and sarcomatoid because they're more aggressive cancers. So the ipinevo attacks it better. That now I would say we are much less likely to operate on somebody with biphasic than epithelial. Epithelial, I think, yes, you you can you still there's still a role for surgery. Biphasic, it's a little bit more nuanced, and more of us, because of some of the bad or some of the results that we saw in Mars 2, are becoming more selective because of that. Those patients with biphasic don't do as well with surgery. And we've kind of always known that, but there was just nothing really to back that up uh until Mars II. And then number two, and now that we have a good alternative, like you were talking about, David, of IP and NEVO, the dual immunotherapy agents that do real very well and you can live longer versus just chemotherapy alone, um, with that for biphasic and sarcomatoid, especially, that yeah, we tend to leave those patients alone now. And that's a big change. And in fact, it's such a big change, David, that the NCCN guidelines now um no longer put biphasic. They no longer add biphasic in the indications for surgical uh evaluation. They just have epithelioid, plural epithelium is epithelium before I remember because when I used to give talks before, it used to not distinguish epithelioid uh only. And biphasic was even in there. Uh, and then now we don't see that anymore. The biphasic word is no longer a part of, oh, then you if you have biphasic, go see a surgeon and then you can discuss. It's it just says plural epithelial uh epithelioid. So I do think that has been a little bit of a change. And and and so I do think, don't get me wrong, Mars 2 does offer a lot of uh a lot of benefits for what they did. They they taught us to be more selective, and then maybe you know, being a cowboy surgeon of the old school days of like, hey, there's no other good treatments for mesothelioma, other than just ripping everything out, um, you know, probably doesn't isn't relative, isn't it, isn't it real and relative anymore, and that we probably should be a little bit more selective, especially with newer uh you know, drug agents coming along that can treat mesothelioma better than what we had in the past, which was really pretty much nothing.

SPEAKER_02 25:46

Well, maybe we could do a follow-up uh podcast after you get back from uh Korea to see if you have a black eye from the Yeah, I'll it won't be a black eye, but I'll be teary afterwards.

SPEAKER_06 25:59

Despite how strong I come out with these statements, the hardest part is you're going up against randomized controlled trial data. And us as scientists, us as doctors, even you as you know, uh lay people, lawyers, nurses, not you know, medical people, that's always what we've been trained on uh scientifically and everything. That the level one evidence, the best evidence is a randomized controlled trial that you can compare this group to this group, and there's no quote unquote biases of looking uh backwards. What else did you want to ask?

SPEAKER_01 26:29

No, I mean that I basically wanted uh him to break that down. Um makes it easier when I'm actually talking to people. Um, you know, a lot of times we'll ask the question, are you having surgery? And and you know, I I saw where it went went from yes, we are having surgery, no, they they aren't having surgery, and now we're back at yes, but different. And which is good because when you when we talk to these individuals, it's you know, to know what you said that you know, the if the doctor is a a well-trained doctor and has worked with mesothelioma patients, I mean, they have the experience, right? You you tend to want to send them over to whomever, which is what we used to do with Dr. Sugar Baker. It's like, you know, we want to send them to someone that knows this cancer. And then it was, well, we're not doing surgery, you know, we want quality of life. So you didn't really send them to anyone in particular. And now we're at, yeah, you do definitely want to go back to sending individuals to doctors that have the experience um in this, and that helps me. Um, Dave knows all this stuff, and I, you know, it's just better to understand, you know, where we are for each one of these uh patients.

SPEAKER_02 27:48

So um, which a couple more questions. How much time do we have? Were we uh uh running out of time for him?

SPEAKER_03 27:52

I have a quick question. Okay, go ahead.

Heated Chemo Vs Betadine Wash

SPEAKER_03 27:55

Oh, so can you just tell me? So I think you told us that you use a beta dyne wash, you don't do uh inter-op heated chemo.

SPEAKER_06 28:01

Right. That's another thing we learned too, right? And it was always dogma before he did a heated chemo. Uh, but yeah, no, I do a beta dynam wash, and and that's being trialed. Joe Freebird kind of showed that in the past, but that there is a clinical trial. I want to say either Dan Miller in Georgia or somebody's doing that, comparing it, doing their surgery with a beta dynam wash versus not with a beta dynam wash. So we'll see what those data are. But we know in the lab, actually, ironically, from the UK, that mesothelioma cells specifically get killed by beta dynamically. That's always a good shame. Um, but whether or not it works in view, we don't know, but why not? If it kills it specifically, you know, and it's not gonna hurt you, why not? And so I do a betadine heated bath, and it gives the more you heat it, right? Uh similar to heated chemo, the the higher kill rate it'll have on cancer because uh heat bursts cells, right? Um, and so the reason why I didn't do heated chemo, stop doing heated chemo, and that's why you need to be at a big center to see. I saw a lot of the the brutalness of heated chemo. I was the one, the fellows are the one doing the heated chemo. Not only does it add another hour to two hours of the surgery, um, they drastically get more renal failure, they drastically stay in the ICU longer, they have way more fluid. You know this. Yeah, you guys know this. Um, but that was just like, oh, well, that's what we came up with, and that's we do it because in theory, but it's never been shown in a in research studies to show that it is in order in a randomized child that it's superior to doing nothing at all, other than you know, meaning doing surgery versus surgery with high talk, uh the heated chemo. There's been no study to show that it's beneficial. However, two years ago, the brigham, our our very own the brigham, did publish data showing that patients that had high talk or had the heated chemo had way longer, uh double the length of stay, not surprisingly, and double the length of acute renal failure. So, and those are really important things that I care about. That's what will kill you in 90 days if you have renal failure, you know, all those, you know, those things. And so I I, you know, I had always I didn't wait for that study uh because it just came out two years ago. I right when I came out of practice out of the Brigham, I knew that I wasn't right, and that's what you learn. You take what you can, you don't take everything, you don't say I'm just gonna be a sugar baker and do exactly what he does, because you learn from what he does and what are some of the stuff that maybe he didn't do. And one of the main things that I saw that was just not worth it at all, not worth the bang for the buck, and and getting a perfusionist in and all this time the surgeon is sitting there, we were just sitting there waiting for the chemo to just you know get all toxic in our face and what and not really help. And the patient has complications, whatever. Um, that I was like, no, I don't think it's uh gonna be beneficial. And and and and sure enough, they're the program finally published because it takes 10 years to look at their whole data um published that heated chemo didn't, even though they have some papers, of course, that are for it and they still do that, but that paper really, really emphasized that the complication rate's just really too high and um and uh and doesn't help improve uh recurrence-free survival. So, yes, you're right. I never uh since I've been out since 2014, I've never used heated chemo. Um, but there's certainly people that use it and and we're not against it. But one of the things, Lisa, that I'm glad you brought that up is in our consensus statement, one of the PICO statements or one of the actual statements is what is the role of uh we call them interoperative uh adjuvant therapy because there's other people, Joe Freebird looked at photodynamic therapy. Do you burn in there? Other people have looked at, you know, you know, obviously the heated chemo and all this. And and we looked at all the data, and sure enough, none of the data supported uh the overall that you should or that we even recommend using heated chemo. In fact, we said there is not clear evidence of using anything in the operating room other than surgery. Um, we didn't say beta dynam was anything. We said none of that data is out there, um, but we reviewed it all, but none of the data was convincing enough or high level enough for us to recommend that you should use heated chemo or some or beta done or anything. We just said it is up to the surgeon essentially. It was basically level C evidence. So we don't condone it per se. There's nothing to say that it was just super terrible, um, except for that one paper, but other papers didn't have some of those complications. So we just said it there's there's no proven benefit, um, and it's a dealer's choice.

SPEAKER_02 31:52

Is that true of both plural and peritoneal, or uh would you say primarily plural?

SPEAKER_06 31:58

Plural. Yeah, peritoneal, a little different. There's a little bit stronger evidence for high-pec uh he did plural uh uh for uh peritoneal mesothelioma. So no, this was just for plural when we evaluated the uh intra-optic chemo, just for plural showing that the data wasn't great.

SPEAKER_02 32:14

Well, I I definitely I wanted to ask you more questions, but I hope this is the last time we get you on it because you've shared some information that truly I think is very important to us and and our because we talk to we're like you, right? We don't we don't get every individual in the world that has meso, but we talk to you know dozens of them every week, right, different stages of their lives. So this is really, really good information.

Local Treatments And New Trials

SPEAKER_02 32:37

But okay, so what about like a an uh a heated immunotherapy type regimen? Anything anybody ever done anything like that yet? I mean, not and it may not make sense. That maybe be the stupid, but uh what do you think?

SPEAKER_06 32:50

No, not stupid at all. I think those are that's the that's the next kind of uh level is doing so I don't think it's uh yeah, or vaccine, people are looking at vaccines. Well, right, yeah, injecting that in right now, right? Injecting a vaccine to imbue the immune response that'll uh attack just mesothelioma uh you know cells. Uh same thing with doing localized immunotherapy. I think that would be fine because it would be slightly less less uh renal failure. The only issue with immunotherapy, for example, is we know it's got a lot of lung toxicity. Um so you can you do keep the lung, but then you add immunotherapy to it. You may have, we don't know this, and nobody's done this yet, but we in theory you can have a little bit more lung inflammation, otherwise known as pneumonitis. Um but I do agree with you, David. Something, uh, something in addition to in our surgery, because I remove it all, but we know that they're circulating around because it's just it's just like a it's plaster everywhere. Um, so and you know, I do think something more targeted where we could, you know, do a spray. Uh in fact, there is a uh the the group at Stanford, it does have a chemo spray. It's just the regular chemo, but it's a spray uh that they do, uh that they spray on it. And they're trialing that right now. They just did the first one. So doing chemo spray. But ideally, but this is just the normal chemo, right? Ideally, and that can cause you know, real fair and all that stuff, and it's just chemo not directed just for mesothelioma, just regular chemo. But what about, you know, something targeted more towards mesothelioma, something local, something additional, um, because radiation clearly with the with the with the data hasn't shown as a routine should be uh improves your survival. And that's the idea of why people use radiation, why we used to use radiation, or sometimes I will use radiation, is because we know we couldn't get it all out with surgery. We tried everything that we saw, but let's radiate all around that area. But the the problem is that a lot of the toxicity with that is still brutal, even with new techniques. So ideally, I would love to have a beta dyne bath that's specific to meso, uh, not necessarily beta dynamite, but some mesochemical that it takes five minutes to circulate, throw it in there, circulate it up, and have it uh be uh killing mesothelioma cells, suck it all out, and that's great. Um and that's you know, that would I think uh be very uh would be very beneficial.

SPEAKER_02 34:56

Any other therapies on the horizons you'd like to um you think are exciting?

SPEAKER_06 35:01

Um

Targeted Drugs Beyond Chemo

SPEAKER_06 35:02

Yeah, so the the PARP, the PAP inhibitors, so there are certain molecules or uh you know genes and proteins that are specific just for mesothelioma that are even different than lung cancer per se. Um and there are certain uh drugs that they're trialing in phase one studies. So other drugs other than immunotherapy, other than vaccine trials, other than CAR T cell trials that are just looking at inhibiting mesothelioma cancer cells on a protein level, um, whether it be injectable or vaccine or uh, you know, uh uh or or you know, pill therapy, uh, those I think would be ideal. Um something more personalized and targeted. Right now, if you think about it, we still only have surgery, radiation, just overall chemo, cysplatin and pamotrepsid, um, and just regular overall immunotherapy, meaning IP NEVO. But again, remember, immunotherapy is not specific for just meso. We use it for all different kinds of cancers. So I think we still uh on the horizon are the ones what I'm interested in are the ones that are going to be targeting more mesothelioma because mesothelioma, as we know, is a different beast in lung cancer, it's a different beast in melanoma, it's more aggressive than renal cell cancer, all those ones that respond well to immunotherapy. Yes, it responds decently well to immunotherapy, but nowhere near what the response rates are for lung and and and kidney and all those other ones where it's traumatic than immunotherapy. Even with the mesothelioma, it's not traumatic. I mean, it's it helps better than chemo, but it's not traumatic enough. They still die, you know, they live four months longer, right? And with the MVD. And so I do think we need more targeted approaches. Um, and even some of the immunotherapy approaches that are coming out now, and I think that uh they were doing it uh Baylor and I guess Terry Taylor and them are guess going to bring it over to Vanderbilt, but they were looking at more novel immunotherapy agents. Again, still immunotherapy, not directly at mesothelioma, but they were newer age uh and and maybe thought to be better at controlling more aggressive uh cancers like mesothelioma. So I think that is that is great. And then lastly, I'm not opposed to doing treatment, systemic treatment before my surgery, okay? But I'm opposed when it's chemo, when it's not gonna really help, and it's not gonna help my surgery and it's gonna like make the patient weaker. But there are some new trials, and again, Taylor's looking at this. Ripley is looking at this with giving novel immunotherapy before um and then doing surgery. They're having trouble accruing because, like you said, nobody wants surgery anymore. And so, how are you gonna even get them in to do trials? So they haven't been accruing, so I don't know if that'll ever pan out. Um, but if we were ever able to show an effective immunotherapy that's not that toxic because it's immunotherapy less toxic than chemo, and it works and it shrinks things down, I I'm all for it. It's not that I'm anti, you know, this neoadjuvant approach because um I'm all for it. Um it's just we haven't seen that yet. And until we really see that, I'm not convinced um that that that you give stuff before um rather than just you know what we do now is like, hey, it's bad right now, they have potal fusions, they have pain, uh, they're you know, they look sick. You see them, they look sick, right? You got to get this stuff out um versus like, oh, let's keep it all in and then make them sicker with chemo and hope that it shuts things down when we know it doesn't. And most of those patients won't make it to surgery. And even the ones that they probably did take to surgery, we don't know. This is the bias that around is trying to Mars too. How how healthy really were they, right? Right, how healthy were they? They didn't include the ones where they didn't operate on, right, that got chemo that were supposed to get surgery, but didn't get surgery, right? Um, they only included the ones that got surgery, and again, how were all of them like super healthy uh and young and everything? And then we know that they weren't. So, anyways.

SPEAKER_05 38:44

Can I just ask one, can I just ask

Getting Oncologists To Notice

SPEAKER_05 38:46

one question? Congratulations on your um consensus article. That was really great. What's been the reaction to it?

SPEAKER_06 38:54

So far, really, really good. In the, but that's just in the thoracic surgery community. Very happy. Everybody's like, yeah, we knew that kind of, you know, or at least it's in the United States, like the big, you know, they're like, okay, yeah, we knew that. Um, I was just I just heard from Raja Flores the other day, you know, like he's like, of course, like, right? That's just what they do because and Andrea Wolf was on our, you know, uh, you know, uh his disciple was on, and you guys know what Andrea were uh was on our consensus statement, but but uh but again it was it's kind of like known. So nobody's like, oh my god, this is like United States surgeons. What I don't know, Ellie, and what that's why I want to bring it to the world, is what do the other people think around the world, the surgeons, yeah, and more importantly, what I need to know, that's why I need to talk about it in ASCO and and in the medical ones. What do the medical oncologists think? Because if I can't change the minds of the medical oncologists, because they're always gonna see Misa, right? If I can't change the medical oncologists of the United States, because they're all they're all bought into Mars 2, then we're not really doing a great thing. We're not, but they're not aware of this yet. Um, you know, Ellie, and that's why I'm so keen on trying to get it out there to more people, because if patients hear about it in your whatever, then they can go back to their medical oncologists and be like, hey, have you seen this? Because I guarantee you they have not, because it's only circulated with surgeons. That's the one bad thing about these cool things or STS and all this. But they're so, I mean, it's not like medical oncologists read our top cardiothoracic journal. Just like I don't read JCO, their top on medical oncology, because it's usually stuff that I never need to see. And if it does something does come up that's cool, that's relatable to me, um, I don't really know about it or hear about it, but it's probably like a year later. And that's why I need to combine that a little bit better, Ellie.

SPEAKER_05 40:29

Yeah. Oh, well, it was great.

SPEAKER_06 40:32

Thank you. Um what I oh good, because you guys don't have anything, but I did want to add this is really good because Ellie and Lisa are on.

The Disappearing Meso Surgeon Problem

SPEAKER_06 40:40

I think they understand this more than others that you guys have to know that I wanted to to bring up, which is another uh which is a problem that I'm really worried about with mesothelioma surgery, even in the United States. We already know Europe and for most of Asia and like around the world, they're not doing this surgery. Um, one, they never really believed in it, and two, they just don't have the experience of doing it because they never really believed in it. Um is that in the United States, we're losing all of our experienced mesothelioma surgeons. They've either passed away or they're retired, like Valrouch, losing Valrouche. Uh obviously she's great and healthy, but she's retired. She no longer does a surgery, she no longer has an office at Memorial Sloan Kettering. Um, right? Joe Freeberg is still around, but like, you know, these people are in their 60s. Um Bob Cameron, Bob Cameron, one of one of the pioneers of pluorectomy decortication, he is officially retired. Okay. Um so we don't have that experience of those people. Harvey pass is great, but he doesn't really operate anymore, I don't think, you know. Um right, and so these are all the people even Bueno still operates, but I can tell you, Bueno's not gonna be around, you know, he's not gonna do this forever. I mean, how old is he like, you know, um, and it's so we're losing not only the people that are like 5,000 times crazier than me, they have 5,000 more clout than me. So people are always gonna listen to what they say, right? They're not gonna have to listen to me yet, uh you know, right? And so uh we've lose that influence. And then not only do we lose those people that are really believing the surgeon that have the most experience in the surgery, because they've been gone for so long or whatnot, we've lost the whole new generation of training surgeons, and especially in the robotic area, where most surgeons don't feel even comfortable doing an open operation. Most robotic surgeons don't know how to do an open operation anymore, and so they didn't train on the air anymore. And mesothelioma is the last of the classic open operations, whether you do polectomy, whatever you do, it's still open. And that we don't have any the older surgeons no longer operating anymore, or or or they don't have the stamina to do anymore, or whatever, even though they believe in it. They're the younger people are even worse, they don't even know. And even so, even if your medical oncologist or your patient gets referred at a major academic institution, there, which is where they think it's gonna be best, those surgeons probably won't even offer the surgery because they don't feel comfortable doing the surgery, even though they're at an MD Anderson or City of Hope. Uh, you you know, even UCLA, uh, you know, Brian Burt, I love Brian Burt, but I don't even think he does much miso anymore. You know, they don't know it's sad, right? But it's because he's into the robot and he's into other cool stuff. And I get it. He loves Brian Burt loves AI. He's a great friend of mine, but like we lose all of that. Um, even, you know, and so I'm kind of that generation X where it's in the middle where I saw both, I see both sides of it, um, the robotic age and the kind of old school age. And I feel this are a good compromise for mesothelioma surgery. Um, but I would say there's a lot less, less of us. I mean, me, Taylor, uh, you know, Sean Grove, maybe, but again, these are just sugar baker disciples, right? There's not many of those left. And even the sugar baker disciples that disciples, Andrew Wolfe was like with there's only a handful of us left. Uh, and we're only across smattered across the country. That even if you did send to a surgeon right now, um, you know, David Ann, who are you gonna send to?

unknown 43:52

Yeah.

SPEAKER_06 43:53

Good point. Name name name name 10 surgeons that you know that do this surgery well. Well, name five. You well, yeah, you guys were biased because I'm on, but like, okay, like you know, and you know, I think that's the problem about like even yeah, Raja Flores and uh Andy Adoro.

SPEAKER_02 44:14

Yeah, is Jacques Fontaine doing any surgery now or no?

SPEAKER_06 44:17

Is he another guy that again another sugar maker disciple that I refer to? Yes, um Marcelo da Silva down in Florida, he still wants to do it and he's still Marcelo's in Texas now.

SPEAKER_07 44:30

Is he?

SPEAKER_02 44:31

Yeah, I think he's at UT. Yeah, he's moved here. That was recent because I just saw very recently.

unknown 44:38

Yeah.

SPEAKER_02 44:39

Not De Silva, Marcelo. I'm sorry. I'm sorry. Um uh Louis um oh Lewis Lewis, yeah, Lewis. Uh Green, Marcella Green. I'm sorry, that's what I was talking about. Oh no, no, yeah, yeah, yeah, yeah.

SPEAKER_06 44:53

Marcelo da Silva's still in or yeah, yeah. And uh I'm sorry, I didn't read it. What's that?

SPEAKER_03 44:59

Is Alex Farabad doing it in Seattle or no?

SPEAKER_06 45:02

He doesn't, but there's another guy that took over for uh Eric Valier. Um retired, and so there's a younger dude down there that he gives him to.

SPEAKER_07 45:11

Okay.

SPEAKER_06 45:12

Um but Alex got really into the robot, so I don't think he does much of it. So there's one person up in Seattle at Swedish, I want to say, or whatever you're doing. Yeah, yeah. Um, nobody really in Oregon that much. I do it. Me and Leah Backis do it uh up here. UCSF doesn't do it, UC Davis doesn't do it. Down south, it's pretty rare. Uh Cameron, Cameron now refers to this new guy who, again, I don't think he does much miso because he's brand new and I've never heard of him. Um, but he seems like a nice guy, Vignesh Ramon uh at UCLA. So they don't refer to Brian Burt anymore. If you go for Miso down there, Cameron says go to Bignesh Ramon, but not to Brian Burt, who's the chief there, and he still doesn't refer to him, and not to Jay Lee. Jay Lee is another guy that can do it, but again, Jay's into his other stuff now. Jay runs a company, he's into the you know, people get into other stuff because miso, I mean it's a morbid disease, right? I mean, you know, fun taking care of him, and we all know that, right? And so, of course, if you go to something sexy and whatever, um you know, in medicine and where the patients will live and not die within a year, right? You know, and that's really what's happening. And the new people, they don't know they when they look at these big surgeries, like the my, you know, the the the new attendings or whatever, they're scared of this, or they're like, oh my god, what you guys are doing is malpractice because you're just ripping, you know, because you have it's old school. So and that's not the way surgery is taught anymore. It's very delicate. It's like you use a robot, take less out. So it's mesothelioma is kind of against what we're moving towards, which is do less, do less, do less, do less. But with meso, it's still an aggressive disease, it's all over the place. But man, have I seen so and that's the problem. All these younger surgeons are anti-meso surgery. Um, and that's what's hard for me. I gotta go up against all that. They have no experience at all, and they they have no wherewithal, and they don't have the experience, but they can go by the guidelines, or they can go by Mars too, they can quote Mars too any day and try to go up against you, right? Uh and that's what they do. And and so there are a lot of surgeons that don't want to deal with that, right? Why would you deal with a high risk surgery for a patient that's probably sick as a dog already, old vet, you know, whatever, you know, that doesn't care regardless, right? I'm just kidding, but it's true, right?

SPEAKER_04 47:11

It's not like especially if you see if you really see it too, right?

SPEAKER_06 47:14

Right. And so why would you put yourself up against malpractice and and people saying this or all that? Because that's what happens in miso. Uh-huh. Uh like, you know, you know, and um uh and so I've been lucky enough, like knock on wood. It's but I will tell you there are a lot of haters out there. Um, in fact, out of the 14 thoracic surgery again, um out of the 14 thoracic surgeons that that I work with, none of them will do the surgery. I'm the only one. Wow, wow. So you can see what an island is like, what an island truly is like right, it really is.

SPEAKER_02 47:45

Yeah, yeah. Yeah. Well, this is the best podcast we've had. We better cut that out or I'm gonna get in trouble. But personally, it was the best one we've had. Thank you so much for very informative.

SPEAKER_06 47:59

Yeah, you're welcome. Thanks for I'm always happy to share and and I'm hoping to get things out. So I hear back from your patients or not necessarily for me to do surgery, but just I like to hear what other people are saying because I don't know what they're saying in Nebraska or Texas. I don't know what Taylor's doing. I mean, Taylor and I talk, but like, not I'm not gonna call operating be like, hey, uh, you know, whatever, because we're just busy. But like, I, you know, I'm I'm always interested in what people around the country are doing because I remember what it used to be like, and now I know what it's like now, which is what I assume that nobody's getting anything done surgically. Um, but I could be wrong, and so uh I I'm always curious to you know hear more from you all.

SPEAKER_05 48:34

That would be fascinating, the numbers surgeries are actually actually being performed now. That would really be interesting.

SPEAKER_03 48:42

That would be interesting.

SPEAKER_06 48:44

I know I gotta look at that. Um I we there's a way to look at it um to see the numbers, but um through the SCS database. But you're right.

SPEAKER_02 48:53

Um you need to have a fellow look it up and then publish it at the next IMEG or something, right? Or ASCO or something.

SPEAKER_04 48:59

Yeah, absolutely.

SPEAKER_06 49:02

Yeah, yeah, yeah. Like we're saying that because it's anecdotally, but I don't know what the actual numbers are dropping. You know, I'm sure they are because that's what I think, but you're right. I don't publish that. Right. So you're right, that would be interesting to really see and to see maybe after 2026, uh, do they start picking up again or not? I don't know.

SPEAKER_05 49:22

Right. Right. Maybe if they yeah, you never know.

Final Takeaways And Resources

SPEAKER_02 49:25

We better let you go, but thank you so much for joining us. And we hope we can talk to you into uh coming back and doing it again later.

SPEAKER_05 49:33

Yeah, good to see you.

SPEAKER_02 49:36

It's great to see you, Ellie and Lisa.

SPEAKER_04 49:38

Yeah, thank you. Take care. Have a great day.

SPEAKER_00 49:44

Thank you for listening to Miso, the Miso Thelioma podcast. For more information, resources, and support, visit our sponsors Danziger and Deiano at Dandel.com.