Treating BCG-Refractory Disease and Explaining NMIBC Treatment Options to Patients

The second part of this NMIBC roundtable discussion, featuring Gordon Brown, DO, Tim Richardson, MD, Bryan Mehlhaff, MD, Chris Pieczonka, MD, and Eugene Cone, MD, addresses the increasing availability of intravesical and systemic therapies, the importance of accurate risk stratification, and the role of education for both health care providers and patients. The panelists highlight the operational hurdles of managing NMIBC in diverse clinical settings, from geographic and compliance issues to the need for navigators and standardized pathways for patient care.

Watch the third segment of this series: Where We Were and Where We Are in NMIBC Trials and Therapies

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Dr. Brown:
So Tim, when we talk about looking at this NMIBC high-risk, say, BCG refractory patient population, we really had an embarrassment of riches frankly in the last, I don’t know, 24 months with new therapies coming to market, looking at historical landscapes, understanding the BCG stewardship story helped us kind of organize these patients in our practice. With the expected potential approvals of other therapeutics in the near future, what are you most excited about in this patient population and can you give us some insights as to why that might be?

Dr. Richardson:
Well, I’m excited about all the therapeutics, but I’m also equally scared because I think we can’t get over our skis. We have to start earlier. We have to actually educate our partners and our pathologists on appropriate risk stratification and identifying these patients. Our pathologists aren’t even giving us the reads that we need. Our partners don’t even know how to risk stratify. And I think if you did that, I think if you really focused on education and had everyone with a good understanding of risk stratification, I think that would roll into all the therapeutics and I think that would motivate people to look for the appropriate therapeutics. I’m really excited about the intravascular treatments mostly. I think we’ve all had some experience in infusion systemic treatments, and I think if you ask most people, the intravascular treatments seem to be where most of the excitement and optimism lies just from a response standpoint.

Dr. Cone:
I think from an organizational standpoint, education is certainly very important, but I think especially once you start talking about scaling it up over a larger organization. We’ve just hired a bladder cancer navigator, and I think that the same way that you have navigators for your advanced prostate cancer space, that’s going to become increasingly important because there are going to be some urologists who are just not that motivated to get involved in the space. And so having that kind of quality check I think will be important going forward organizationally.

Dr. Brown:
There are a variety of factors which play into therapy of choice, trying to personalize treatment, not only disease-facing factors, but there’s access, there’s patient factors, and we’ll kind of drill down into this as we go deeper into the discussion a little bit. However, just kind of top of mind, what would be the first one or two things? Obviously disease is always going to be primary, make sure they’re on label, but are there access issues, number of interventions a patient has to go through, the ability of cost, and we’ll drill down to some of these as we go through the discussion here. Any of these come top to mind, which would be real inflection points or really high priorities for you is as treating urologists in high volume bladder cancer clinics that would cause you to choose one therapy over another potentially?

Dr. Richardson:
At least in my region, the most common thing that we run into is geography. Many of our patients drive four hours to see us. And so coming in every two to three weeks may not be doable. And we run into that into a lot of different disease states and things in our practice. And so that seems to be more of a factor than whether it’s access from an insurance standpoint or the health of the patient for us anyways.

Dr. Mehlhaff:
And geographic for sure. But just compliance too, just getting people to come in for three month cystos, we have a whole process to rope those people in and make sure that people follow up. And so distance frequency, just compliance and flight risk of a bladder cancer patient that we’re always worried about.

Dr. Pieczonka:
I have kind of an out of the box thought on this as I was thinking. So there’s going to be a whole litany of immunotherapy products that are going to be in this space and there are going to be some that are not immune-based. And as a physician, I’m very in tune with, I think immunotherapy is a good thing. I’m sort of pro-vaccine, but there’s a lot of patients who are not. So I think as we sit around here, perhaps with the exception of yourself, a lot of us are in smaller areas and we have a huge rural population that is very immune therapy adverse, just generally speaking. And that’s a tough nut to crack when you talk to them about a variety of things. And with where I think this is going to be headed in the next couple years is that you may suggest the best therapy for the patient that you might think may be immune-based, and the patient may have perhaps some biases and say, no, Doc, not going to happen.

Dr. Brown:
Yeah, I think it’s actually a critical point. I didn’t mean to interrupt you, Gene, but I think mechanism and how we explain mechanism of action, really two questions to the group. Does mechanism matter? And does it open up the door for sequential therapies as a therapeutic paradigm in patients who may progress on first or second line therapy even in the refractory space, especially in the CIS patient, right? Maybe not the papillary patient due to risk concerns for progression, but certainly in the CIS patient population. I’m interested to hear, Gene, what your thoughts are. Does mechanism matter, people adenovirus adverse? Right? How detailed is that conversation that we’re having with our patients around what the MOA is of various therapeutics? And I think Chris brings up a great point. Patients may just say, I don’t want to have an adenovirus in my bladder, for a variety of different concerns.

Dr. Cone:
Yeah, no, I think it definitely matters, and I think that you do need to get into the mechanism at least a little bit with patients. It’s a lot easier for a patient to understand an intravesical chemotherapy for example, because we’re giving you the same thing. A lot of the same patients that Chris is talking about also have very preconceived notions about chemotherapy. But you can get over that very quickly by saying there is no systemic absorption. You don’t absorb urine out of your bladder, you’re not going to absorb the chemo. And they get that there’s this highly toxic thing in their bladder that’s going to kill cancer. And then if you start veering into some of the other mechanisms of action, that’s a little bit of a murkier conversation, especially if the patient has lower health literacy.

Dr. Mehlhaff:
But I think it’s all presentation, right? I’ve not had a sipuleucel-T patient tell me, no way, that sounds too much like a COVID vaccine, or something like that. So I think it’s how you describe it. We’re modulating your immune system, training your immune system.

Dr. Pieczonka:
But the thing with sipuleucel-T is there’s sipuleucel-T and then there’s not, right?

Dr. Mehlhaff:
Yeah.

Dr. Pieczonka:
So I think in this case there’s immune therapy and then there’s potentially not. And so that might be as part of it-

Dr. Mehlhaff:
It’s good to have alternatives.

Dr. Pieczonka:
I think that for my standpoint, I struggle to understand the mechanism of action of all these different therapies. And so for me to be able to cogently explain that to a patient, I don’t know how we do the right education on there. And I think one of the charges that I think we all need, and this is probably with LUGPA, partnering with us for nice educational bite-sized chunks for our patients that are at a level that the patients can understand.

Dr. Brown:
Yeah, I think Gene used a term called health literacy, which is extremely important to have good bidirectional conversation with our patients. One of my mentors when I was a resident actually used to use an analogy of shock absorber, right? So you raise or lower your level of discussion based on the consumption ability of the person you’re discussing the therapeutic with, right? And we have all a variety of ranges of intelligence, health literacy folks that come into the clinics themselves. So I think it’s extremely important, but I do think trying to have patients understand what they’re getting into, what the baseline operation expectations might be for therapy is going to be important.

Dr. Cone:
I think that one of the things, and this is probably just they haven’t been around for as long, so I’m not as practiced on it, but I have a one-liner for most of the therapeutics in this space. Immunotherapy is loosened up with [inaudible 00:15:23] on your immune system so that it can go after the cancer cells in your body. Intravascular chemo is putting poison in your bladder that doesn’t get absorbed by the rest of your body. BCG is putting an immunotherapy in your bladder that’s going to piss off your immune system, bring it to the area, and it kills the cancer. I don’t have that for the adenovirus and especially for the non-adenovirus vector therapies. So some of that’s just practice and I need to figure out the one-liner, but it’s not as intuitive.

Dr. Richardson:
The difference in mechanism of action can work to your advantage as well. And we find that in our clinical trials, we have these patients that have failed BCG, which is obviously an immuno type of response, type of therapy. And we sell these clinical trials like, hey, we have a different mechanism of action, we have a different way to attack this. And I think they like that message. It can be the same once you have approval in the therapeutics

Dr. Brown:
We have, and I know I’m sure you do as well, our mid-levels take a lot of this lift, quite honestly, and we’ve taken some cues from other colleagues across the country and have developed cards basically that these patients will get prospectively and that they’ll understand this is the landscape of where I’m going to go if I’m going to get X, Y, and Z therapies over the next 12 months, for example. That wasn’t driven by me, that was driven by my nurse practitioner. So it all kind of full disclosure, but it really is a nice way for them to understand what their expected burden of visit is, when they’re going to get a scope, when they’re not, when they’re going to get a potential scan, when they’re not. And so I think that that helps them formulate a plan or a vision for at least a calendar year in their mind what they’re to expect, assuming they continue to respond. Has anybody thought about doing anything along those lines?

Dr. Pieczonka:
That’s a great idea. We do that in our research patients. One of the ways that we sell a research patient on a study is that we take the worry off their shoulders and they’ll know exactly what they’re going to be doing. And we do not do that on our commercial patients. I really like that idea actually, because that way the patient knows what they’re going to get and they know that the bladder cancer space is going to be something fairly intense in terms of follow-up, no matter how you look at it.

Dr. Mehlhaff:
You’ve already explained the regimen of cystoscopies and there’s a program, so I think you can build on that same program, I like that, too.

Dr. Pieczonka:
That’s a great idea. Yeah.