Gautam Jayram: Thanks, Ashish. Great to be here.
Ashish Kamat: So hey, Tam, you and I talk a lot. And we sometimes talk about what to do in different parts of the world. Sometimes we talk about bladder cancer. Today we're going to talk about bladder cancer. And some of the things that I really would like you to share with our audience, because as you know, the audience here for UroToday, it's urologists, but it's urologists in every part of the world, not just here in North America, but Canada, Europe, India, I mean, in different places. And sometimes sitting in academia, I'll write and I'll publish and I'll talk about, "Hey, this is the way we do it." Not realizing that there are some practical real-world challenges that you all face that you have so eloquently voiced in different forums.
So first just introduce yourself for our audience and then walk me through your thought process with how you evaluate these different drugs in your practice.
Gautam Jayram: Yeah. Again, great being here and a pleasure to talk to you about this. Obviously, you've done so much work in this space. So I'm Tam Jayram, I'm a uro-oncologist in Nashville. I've been practicing for about 15 years. I have a special interest in bladder cancer and really optimizing care pathways and oncology pathways in community practice, which has been a lot of my efforts. And also, we have a large clinical trials program. So I've seen a lot of these drugs come from Phase I, Phase II, Phase III trials. And one thing that I have the ability to do, which is really nice, as a community urologist, is see these drugs and have them protocolized for how to deliver these drugs in a trial setting. And that gives us a lot of information as to how they are going to behave and how they're going to be taken up in the real-world.
And that's been, I think, very interesting. And it's part of the reason that our practice adopted checkpoint inhibitors somewhat early because we were able to administer them on trial and we were able to see how it worked and manage the side effects on protocol. And that obviously led to us being able to do this in the real-world. So a couple of things that I think the audience should know is there are certain limitations to a lot of community practices.
Ashish Kamat: Tam, you said something that really made me pause for a second. And let me ask you this because you talked about doing it in trials, and that's of course how you get access to the drugs. And clearly you and your group know this, but how many people do you think really, in community practice, and let's just stick to North America for now, actually understand the true definition of BCG-unresponsive disease and how many are just using it in BCG-exposed patients? Some patients get BCG and then they're sitting in front of the doctor and they say, "Hey, BCG is not working. What next?"
Gautam Jayram: Yeah, it's interesting. We asked that question at a fairly large LUGPA forum a couple years ago is, how many urologists feel comfortable with the definition of BCG-unresponsiveness? And it was about 30%. So it goes to show you that this is a nuanced space and especially in the community where the vast majority of urologists see a lot of different types of urologic conditions. You do have to, and that's one of my messages to our peer practices, has been, if you're going to do this endeavor, you need to build out a program, you need to have a champion, you need to have dedicated people to do this. People like yourself in academia have been instrumental in showing the value of high-volume bladder cancer physicians and their impact on outcomes.
And so we've tried to build some bridges towards that end in terms of identifying people within the practice who are really interested. But yes, so the short answer to your question is, is the awareness of really what represents BCG-unresponsiveness is not terribly high. It's getting better, I think. I think all of these drugs has improved that as you know, because we're forced now, as urologists, to understand the definition. But also the point of BCG-exposed, there are a lot of patients who have haphazard BCG administration. And we've talked about this.
One of the main lessons from some of the recent BCG-naive trials that we've seen is that BCG can be extremely effective when done well, but yet here we are where we see a lot of BCG poor stewardship where we don't see maintenance being done, we don't see patients getting repeat induction. We see patients being lost to follow up all the time. So that is still a big area of... A big gap, unmet need in community practice.
Ashish Kamat: So now walk me through, obviously as part of the IBCG, and our guidelines and recommendations, and even here at MD Anderson, we say, "If somebody meets that BCG-unresponsive criteria, clearly offer them a clinical trial." But outside of a clinical trial, we tend to use Gem/Doce. We use it based on multiple small series, then multiple large pool series, European data. I mean, data that essentially shows that gemcitabine docetaxel has very good efficacy in this group of patients.
But I know that it's a time and money loser in many practices, and that's a real constraint that I hear from folks in the community. So talk to me a little bit about how you use Gem/Doce, if at all, in your practice and how you would recommend people operationalize that if they were thinking about it.
Gautam Jayram: Yeah, so inherently it's challenging. In independent facilities, there's an ordinance, a Medicare ordinance called USP 800. And strictly speaking, what it says is that if you purchase chemotherapy or any systemic agent and you change the way that it's administered, you need to have certain facility infrastructure protocols in place. So when you buy gemcitabine, when you buy docetaxel, it's packaged to actually be delivered intravenously. And so what you have to do is you have to open the package, you have to mix it, you have to compound it, and then you have to repurpose it to deliver it intravesically. And so in order to do that and be fully Medicare-compliant, you need to have a chemotherapy hood, you need to have a negative pressure venting room, you need to have an oncology-trained nurse, you need to have hazardous waste disposal.
Now, there are some practices that have figured out ways to accomplish that, but you can imagine, largely speaking, across the country, not every practice is going to have that. It's a huge cost. And then like you said, you add to it the fact that you're not really getting reimbursed for the time or the effort to do all of those things. In fact, you're going to lose money on that because those medications have to be compounded. Those compounding pharmacies charge an extra fee, which you don't get recouped. So big picture is, it's been a slow climb in independent practice or in community practice. One thing that we have suggested years ago in LUGPA is to make associations between either hospitals or oncology practices because they have advantages in purchasing.
As we know, there's 340B pricing for a lot of hospital facilities that make Gem/Doce maybe more attractive in the setting. And so our personal experience, I've written up a protocol on how to administer the drug, what pre-medication, post-medications to give, how to do the catheterization and everything. And I've worked with our local hospital system to do it, and so we do have access to do it. And I would say that a decent amount of practices have something like that, but it still is a little bit different because you're losing control of the patient.
The patient is going elsewhere, you have to get the records, you have to figure out how things went. It's a lot different, as you know, than when it happens under your own roof and you generate the notes under your own EMR. So utilization of Gem/Doce is still quite poor in the community. And as a result, we have leaned a little bit more on the commercially available BCG-unresponsive treatments.
Ashish Kamat: So now walk me through, there's a patient sitting in front of you, BCG-unresponsive, CIS with maybe some TA disease, I mean the typical patient. How are you, and let's assume our audience is in Disneyland and they have access to everything, how are you going to talk to that patient about the different options and how do you arrive at what to give a particular patient?
Gautam Jayram: Yeah, things are changing quite a bit. Now we have four intravesical options and now has tripled in just a small period of time. But the contemporary discussion is really talking about the cystectomy aspect of this disease, which is obviously a driver for patients to seek other therapies. So you talk about how the gold standard is removal of the bladder. And a lot of patients that come to me have heard about this or they've read about this and they say, "What else can I do?" And so they have a high appetite for other treatments.
And then you go through the treatments and I think a big part of the discussion is going to be the logistics of the treatment, but also how the patient's bladder has fared so far. We've talked about bladder preservation is great, but there needs to be a good bladder to preserve. So in patients who have tolerated BCG okay, they don't have really terrible symptoms, then you begin to list the options. And I kind of start breaking them down by how often the treatments occur, and generally, my take on efficacy and durability. Which is important, but I will tell you, in the community, it's not as important, especially to patients who are just looking to do something other than removal of their bladder.
So we talk about the agents, nadofaragene and TAR-200, N-803. We talk about those agents and we talk about the dosing schedules, how often they'd have to come to the office and what my general take is on durability and efficacy. And the other thing that's quite important both to the patient and the practice are the economics. Some of the treatments are a little bit more involved economically. Some of the treatments for our practice are involved economically in terms of the number of treatments you have to give before you get any reimbursement back. That's why there are some benefits of these treatments that maybe are not as frequent. Because, as a practice, you have some time to, what I call, test the waters in terms of how are you going to get paid back, how quickly are you going to get paid back? Can you file an appeal? Is the insurance company willing to play ball?
As opposed to some of the other treatments where you're giving six, nine of these treatments before you can potentially see any reimbursement. And that puts a little bit of risk into any big practice and will scare potentially any big practice. Those are things that, at this point, we're used to that, and if you have a cancer center that's been doing advanced prostate cancer therapies, we are used to capital outlay for these drugs. But it still doesn't make it any easier to shell out a huge amount of money with a little bit of uncertainty. So things like established J-codes and how your peer groups are performing. And we all have big consortiums in the community of, okay, well, are you getting paid? Okay, we'll try it. If you're not getting paid, we don't want to be an experiment here. So those things remain very, very important, especially with these high-priced drugs.
Ashish Kamat: So Tam, someone in a small town somewhere in the United States really wants to keep their patient local, which I think is great. Patients should not have to travel to get good care, and is listening to this and is thinking, how can I start using these drugs in my practice? I mean, in short, because I know you could talk about this for an hour, but in short, what would your advice be to our colleague out in a small town in rural America, for example, on how to go about doing it?
Gautam Jayram: The one nice thing about BCG, as you know, is it's extremely familiar. That's the one thing that is still very, very important, is familiarity of intravesical therapies is important. Every urology clinic around has a nurse or an MA who gives BCG or has the capability of giving BCG. So what I would first say is, this isn't foreign, because a lot of rural urologists are very concerned about these new therapies, "What do they entail? Oh my gosh, I don't have the technology. I don't have the infrastructure." I will say a lot of these companies with these drugs are making them easier. We've seen initial storage and handling requirements become a lot easier as these drugs have gotten more mature. And because these companies know not every practice has a minus 60 degree Celsius freezer. Not every practice has the ability to do this stuff. So they're all coming out with different iterations of the product label and the product storage to say, "Okay, well, we've tested it and we're okay being in a regular freezer. We're okay being in refrigerator for a week," et cetera.
So my first thing I would say, this is generally intravesical therapy that you're familiar with. And then to try to develop some sort of team-based approach if you can, which includes a pre-authorization specialist that's going to need to be able to understand the finances for your practice, also be able to have good communication with the sponsor and the sponsor's financial team. A lot of these sponsors now have really sophisticated financial and billing teams that will help your practice. But then also have a point person for the delivery and for the management of the treatments. And so some treatments are just catheter-based as we know, and you place them and you want the patients to be able to call if they have any issues, and you manage those toxicities. Some treatments are more involved and you need a provider to potentially place the treatments in the bladder. But I think developing some sort of team-based approach.
And I think one thing that I've learned is, yes, there are many different drugs here. There is going to be a path of least resistance for a lot of practices. Which drug is easiest for you? Which drug makes the most sense? And so you don't necessarily need to offer every single treatment. And that's, I think, a big point that we've talked about. Offer the treatments that you feel most comfortable with, economically make the most sense, and your practice seems to operationalize well because I think we would all agree being able to offer them something is better than not being able to offer them anything at all. And at this point, offering every single treatment may not have massive value for the patient.
Ashish Kamat: Yeah, I fully agree because people will often ask me, as they have, I'm sure, asked you, "Which is your number one choice?" And I'm like, "Well, it's not a number one choice. It's based on multiple factors including patient preference." Because sometimes the poor patient can get their grandson or granddaughter to take him to the clinic once a week or twice a week and they just want to come once every three months. And sometimes patient's like, "No, I want the kitchen sink thrown at me. I don't care if you have to put something in my bladder every three weeks. Please do it." So those practical issues, and then everything you talked about.
Tam, this has been incredibly useful. And the folks at UroToday, I'm sure they would be more than willing, if you have any links to any of the protocols or things that you mentioned that you can send us and they could put down there, I think our folks that listen to this would really, really benefit from that. So I really want to thank you for taking the time and sharing it with us today.
Gautam Jayram: Absolutely. Always fun to talk bladder cancer, Ashish.