Joan Palou: Pleasure.
Ashish Kamat: And Akshay Sood. Professor Akshay Sood from OSU. Thank you for coming, Akshay.
Akshay Sood: Thank you.
Ashish Kamat: I forget that you were with us just a short time ago in MD Anderson and now you're full-fledged rapid fire debate, all of that stuff. There's a lot of stuff happening here at AUA this year in bladder cancer. It's really exploded. And one of the things that I'm really excited about is your debate at the International Bladder Cancer AUA Forum because it's a very relevant topic today. There's so many drugs being developed in this intermediate-risk bladder cancer space. Some of them very expensive, some of them very toxic, and I'm really looking forward to hearing what you have to say. So Professor Palou and I have done this talk many times. This is sort of your first. So let me start with you. What's your sense as to the best treatment today for patients with intermediate-risk bladder cancer?
Akshay Sood: I think I have to give credit to you and Dr. Polo for what you have done over the past almost two decades, how you've stratified patients because I think we used to think that intermediate-risk is just one disease, but I don't think that's true. So when I see patients in the clinic, I do try to stratify them into intermediate and then kind of low, intermediate, and high within that intermediate-risk disease. So I don't think we can treat them as one disease. So I think based on what I see and kind of based on what the patient's overall health status is, I try to counsel them on how we want to follow them, how we want to treat them, and like you said, we have so many different options now. So I think based on that risk classification, I try to counsel them what different options are.
Definitely I would say for intermediate and high-risk, intermediate-risk disease, I do try to offer them some form of therapy. For intermediate-risk disease, I will usually do kind of office, maybe biopsy. For high-risk, I do tend to take them to the OR for URBT followed by some form of either BCG or intravesical chemotherapy. I've only done a handful of these newer chemoablative treatments for either low or intermediate-risk disease, intermediate-risk disease patients, and they have been doing well, but it's a short follow-up that I have.
Ashish Kamat: So Joan, you and I have been discussing intermediate-risk bladder cancer for decades now, and in 2014 is when we had the first consensus on how to risk stratify within intermediate-risk. Over the years, you've done a lot of work in this area. So before we go into the debate topic, share with the audience how you recommend people evaluate a patient with low grade intermediate-risk disease.
Joan Palou: The thing is that when we treat these patients, then the important thing is the follow-up because intermediate-risk group is In general, we could say it's a low grade multifocal recurrent tumor. That's it, and to simplify from the daily practice. When we take these patients, we see that some of them is just one or two or three small recurrences. Some of them, you will see the bladder full of recurrences and some is the first recurrence or multiple recurrences. So I think these are the things that have to be clarified up front in order to decide with the patient, and also important is the follow-up. If we do so many cystoscopies, we will detect very small tumors. We don't do so many cystoscopies, we will bother less the patient probably because this is not a killer, and the patient will be happy not to have so many cystoscopies and probably will diagnose them. They will have a few tumors but not so many follow-ups, cystoscopies, cytology, whatever. So I think there are a lot of things that have to change and are changing but have to change a little bit more.
Ashish Kamat: Yeah, I think one of the important things that we contributed to the IBCG, and you both are part of it, is getting this into the NCCN guidelines because there were too many patients as you mentioned, getting too frequent cystoscopies unnecessarily and small tiny tumors being taken for major resection with potential complications from general anesthesia, etc. So Joan, let me ask you now, when you have a patient that you are considering with low grade disease and just the kind of patient that you mentioned, how do you go about telling the patient whether you would choose between say active surveillance, fulguration in the office, ablation, how do you decide what you're going to use?
Joan Palou: Yeah. In our center, we have quite established that first we do the follow-up in our patients combining cystoscopy and ultrasonography. So since in general, in our patients in the primary tumor, we do cytology in some multiple biopsies because you know 10% of low grade tumor have CIS. So some of these patients are already out. So we know in the follow-up, we don't have to be so worried about an undetected high-grade recurrence. So we combine normally ultrasonography and cystoscopy and they are really happy because patients say, "What's the neck control?" Ultrasonography. Wow, very good. So we don't have this instrument in my body.
So in general, when we detect by cystoscopy one, two, three small tumors, at the same time just we fulgurate. That's it. So it's solved. When we do the cystoscopy, we fulgurate and that's it. Also, then it depends on the age and risk of the patient. We train that in very all and fragile patients that we treat a low grade tumor, even if we diagnose a small tumor, I wouldn't say active surveillance. We just do not surveil these patients because if we have an ASA4 85 years, why to bother him about this? So normally what we say to those patients and we are just taking all these patients into a database that quite often nothing happens. What we say, if you bleed a little bit, drink more water, if you bleed too much, come to our center, we will do a TUR, whatever, and I can tell you that very seldom they come back to the center.
So I think these are the two options, and also if the patient is afraid having some interventions or TUR, active surveillance is a possibility, but we know at five, 10 years, the majority of patients finally have the TUR, but I think these are the two opposite positions, just do nothing in very old fragile patients, do something if there are not too many. Then the patients, and they send to me several patients that sometimes they have two or three fulguration TURs per year. I think these are the patients that we have to do a good TUR plus PDD because when you use PDD in those patients that you see, for example, four, five tumors, you put PDD on and you see one, another one, and these are the patients as if you do a complete TUR with PDD, and then some adjuvant treatment from two or three coagulations per year go to one every two years or every three. So also, I think this is an important point to consider.
Ashish Kamat: Yeah, no, these are great points that you raise. I think in the US, actually you practice here, I think it'd be very hard to tell patients that we will do absolutely nothing. It's a cultural thing. They will just go to somebody else, right? The trust level might not be quite as much, not in the physician, but in the fact that patients will be able to take that because there's that stigma that's associated with it, and when we talk about active surveillance in many places in the world, we include fulguration. So active surveillance means not going to the operating room, not having general anesthesia. I think just for the audience, we want to make that clear because if you do cauterize in the office, why not? You see it, patients right there, you can just zap it and the patient doesn't have to worry about it, right?
So I think active surveillance for bladder is different than active surveillance for prostate where you're truly doing nothing. In bladder, it means not taking the patient for general anesthesia. I think that's something that we need to educate more people about that's what active surveillance means. Actually, now coming back to the debate topic, right? You were tasked on talking about ablation. So tell us why you think, at least for the debate, ablation is the way to go.
Akshay Sood: Yeah, as you kind of clarified, agree that I think in US, I think watchful waiting, so to say, will be kind of not accepted very well by patients. I think ablation is really good as Dr. Palou mentioned that I think if you see small tumors, I think they're very amenable to office ablation. Patients tolerate it really well. I know some of the trials have instilled lidocaine in the patient for 30 minutes to make them comfortable, but I actually kind of call it incidental. The patients come in for cystoscopy, you see one or two, one, two millimeter tumors, you get the equipment ready. It takes maybe five more minutes to do that. Patients are very happy. You get the cytology or you get the pathology from the biopsy. You're done, they don't want to go to the OR, and I think as long as you explain to them that these tumors can come back, they do frequently come back, but they're really a killer.
I think patients are very happy. So I think that's why and a lot of patients are old and frail. I think it's so hard to coordinate their kind of care in the OR. They have to undergo kind of pre-anesthesia clearance. So many times have to stop their blood thinners, things like that if they're on blood thinners. We don't do always ablation on blood thinners. We will have them come back, but many times we can do that and they safely go home. So I think they're very happy from a patient perspective. It's very well tolerated, and I would say in my limited kind of follow-up of my own patients, I rarely seen if any that have kind of progressed and the data kind of supports that. I think the other part of ablation I would say is the chemo ablation, which I will also touch upon.
Ashish Kamat: Yeah, that's what I want to ask you about because the other ablation you're talking about is what Professor Palou mentioned already, but the big elephant in the room is the chemoablation with the newer agents that have been approved by the FDA are quite expensive and patients are asking for those. So how do you factor that in?
Akshay Sood: Yes. I usually, I think in my mind, how I'm trying to do that, if you have a single focal recurrence, low grade recurrence, but a single, maybe big, maybe one to two centimeter recurrence, I think those patients can be more easily managed by maybe a TUR because it's a single focal recurrence and then maybe adjuvant therapy, but if it's a small multifocal recurrence, I think even with the help of PDD, it's quite hard to completely clear these patients and maybe there is some kind of a more kind of a field effect going on in the bladder epithelium.
So I tend to favor that chemoablation definitely in those patients who are having maybe more than one recurrence a year and it's a multifocal, and multifocal, not just two, three, but more maybe five plus, and maybe more even on PDD. I think that way, at least in my mind, I feel that I'm not putting a lot of pressure on healthcare from these costly drugs, but at the same time, I'm giving these patients the best treatment. So for unifocal, I would say I'm doing maybe a TRBT or an office ablation, but if they have a multifocal high volume recurrence, then I'm leading more towards a chemoablation pathway.
Ashish Kamat: So Joan, what do you think about that? Because again, the trials have shown that with the MitoGel, for example, on the bladder, you can ablate and avoid TRBT in excess of two thirds of patients, but it comes at a cost, comes at a cost of the drug and it comes at other costs as well. So how would you factor that in?
Joan Palou: Yeah, I mean chemoablation and immunoablation has been published for years. There are several Japanese papers 20, 30 years ago that the bladder full of tumor, they put some chemotherapy inside and see the responses. The thing is, do we have to do and at which cost? And also the patient has to come several times. So if the patient is living quite far, they have to come several times to put the treatment and then we have 50, well from 40 to 60% response. What we know is that those who respond, these are the ones that are going to do very well in general, but those who do not respond, then you say, "Well, finally, after six installation into the bladder, now you have to come in and do a TUR." So I think we are not used to do this in Europe in general as a chemoablation and even less with all these expensive treatments, I mean then there is no doubt.
But with mitomycin, for example, the responses are not so bad, 40, 50% or with BCG. You can put BCG and 60% of the tumors will disappear. So it's not so bad, but I'm sure if I ask a patient to say a patient with some experience with adjuvant therapy, TURs, and so I say, "Look, I'm going to put you six installations and then if it doesn't work, we'll go to the TURB." I don't know, maybe this is a question that has to be asked and to be promoted. In patients with experience with all the treatments to say, "What would you prefer?" Probably I would say the patient would say, "Okay, common ones, clean my bladder, and then if necessary, have some adjuvant treatment." Probably, I don't know.
Ashish Kamat: Yeah, I mean these are important points, right? Again, Dr. Sood, you're too young to remember the days when we were doing immunoablation with BCG and other studies, but DaBlaCa and others have been published. Now, I'm going to switch topics a little bit, but stick with the intermediate-risk just in the interest of time. In some of the studies that looked at ablation, chemoablation, head to head with TUR, the reason they look good is because the TUR results were so poor. A large percentage of patients had residual, I think, disease at three months, not recurrence because if we do a good recurrence for low grade tumors, they should not recur at three months. So the quality of the TUR is very important and that's something that you are leading this year at the IBCG retreat, the quality of TRBT, but tell me your views as a young urologist and your views as a young urologist as well who's been around a little bit longer on how we need to-
Joan Palou: He's a good friend.
Ashish Kamat: How we need to improve quality of TUR, especially for these group of patients that have multiple recurrences.
Akshay Sood: Correct. I agree. I think one, I think just having a checklist really helps and we do synoptic op notes and it's not just for documentation. I think it just makes you think that way, that when you go in to do a procedure, you follow all the steps. So I do use PDD quite often, especially for low grade tumors because I do think even if you don't miss CIS, you can still miss small recurrences that can come back, like you said, residual disease in three months, but I think just I've kind of switched a lot to en bloc too.
I think it really is a good technique and I don't use any special equipment. I think just with the TUR loop, you can do a really good en bloc. So if I have a big tumor, I do en bloc, make sure that we are resecting the tumor completely, en bloc if feasible, send a separate deep specimen too, even though we think this is a low grade disease, do a full cystoscopy using different lenses to make sure there's nothing missed, use the PDD and always give intravesical chemotherapy at the end of the TRBT. So I think those are the key things I would think make a TRBT a good TURBT, and yes, I agree. I think that can maybe offset some of the differences we have seen in these trials.
Ashish Kamat: Sounds like they had good training at MD Anderson.
Joan Palou: I think so. They say it's a good center.
Ashish Kamat: And Joan, in closing, what would you share with the audience?
Joan Palou: Well, I think that the concept of a good TRBT, I mean I've seen some time courses that I'm doing a TRBT. I said, "This is a TRBT?" And I remember some years ago I had a prominent urologist from United States dedicated to bladder cancer and we did several cases in our OR of TUR. I said, "What are you doing? You are perforating here. This is a complete resection of a tumor." So I think this is important. I mean of course we don't have to perforate, but not to be so afraid of perforating if necessary, of course, but I think globally we have to do a good resection because also quite often I see people doing TUR of the main tumors and then all the smaller ones, but if you do only small coagulation, I'm sure that cells around are still there.
So I doubt a little bit about the coagulation. That's probably if you have a very tiny small tumor, two, three millimeters, you can burn it quite nicely and quite completely, but if you have quite a lot, I think a good TUR makes a better job, but I think that we have to balance and also is what's a good TUR? Do we have courses, videos to show what could be established as a good TUR? We don't have. We have thousands or hundreds of TURs on YouTube or whatever. I do like this, I do like that, but to establish a little bit the rules and how to do it because also I've seen en bloc resections that people go very close to the tumor, so it's going to be positive margins for sure. So I think all these things have to be improved and shown clearly to the urologist and the new generations of urology in order to do a real good TUR.
Ashish Kamat: Absolutely, and that's actually a perfect plug because one of the things that we're doing with the IBCG retreat this year is tackling the importance of good TUR, but also developing a video library that people can go for access for training to see how Professor Palou does his TRBT, how Professor Sood does his TRBT so they can say, "This is what we should aspire to." Right? Gentlemen, thank you so much for taking the time. Always a pleasure.
Akshay Sood: Thank you.
Joan Palou: A pleasure.