Novel Therapeutics and Personalized Therapies in NMIBC

An expert-led discussion featuring Gordon Brown, DO, and a panel of urology specialists—Tim Richardson, MD, Bryan Mehlhaff, MD, Chris Pieczonka, MD, and Eugene Cone, MD—explores the evolving landscape of non-muscle invasive bladder cancer (NMIBC), focusing on patient identification, risk stratification, operational challenges in clinical practice, and emerging therapeutic options. Key topics discussed in this first segment include the impact of recent trial data on treatment strategies, the role of TUR quality and pathology in guiding care, and the potential for precision-guided therapies in NMIBC.

Watch the next part of this series: Treating BCG-Refractory Disease and Explaining NMIBC Treatment Options to Patients

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Dr. Brown:
Hi, welcome everybody. My name’s Gordon Brown. I’m joined here today by four of my colleagues, Dr. Tim Richardson, Dr. Bryan Mehlhaff, Dr. Chris Pieczonka and Dr. Gene Cone. We’re going to talk about some current updates in non-muscle invasive bladder cancer. Welcome everybody.

So, thanks for spending the next kind of 45 minutes or so with us to kind of walk through some of the patient identification issues, change in treatment landscape, some recent trial results. But I want to hear first from everybody. What are some of the highlights that you see in a changing landscape of the management of folks with non-muscle invasive bladder cancer we’ve seen in the last six to 12 months? Tim, why don’t we start with you?

Dr. Richardson:
Well, there’s a lot of them, number one. It’s kind of scary to think about how many of them are out there in our practice. And with all these exploding treatments and how things are changing rapidly, it takes me back to when prostate cancer changed. And so we’re going to have to be nimble and quick on our feet to change how we operationalize things in our practices. And currently, I would estimate most urology practices, everyone in the practice treats bladder cancer and that may not be the case moving forward with so many changes in therapeutics coming out.

Dr. Pieczonka:
I hearken back to the days when I thought I knew a lot of stuff about prostate cancer and we had created advanced prostate cancer clinics and some of my colleagues around the country have had bladder cancer clinics. And as we started to, I think we’re going to get into some of the research here in a little bit, but I think that the landscape and the number of patients that are there for non-muscle invasive bladder cancer dwarfs what we see for advanced prostate cancer. And I think how we operationalize this and like what Dr. Richardson was saying, who’s going to be the purveyor there? Are we going to have advanced bladder cancer specialists? Are we going to have products that may be more urology friendly and don’t have to be the specialist upon all the specialists? So I think it’s going to be a really exciting time over the next couple of years.

Dr. Mehlhaff:
I also think there’s a lot of work to be done. We started advanced prostate cancer, you realize the variance in care and all the options. And I think that variance in care with bladder cancer is potentially exponentially larger. I think if I asked my patients, is your patient high risk, low risk, they would probably tell me whether they’re high grade or low grade. And this whole concept of risk is not really sunk in yet. And you saw that a lot when we tried to operationalize BCG. Like anybody who was supposed to get BCG, we centrally referred that and then you were like, oh my gosh, the variance in care of just giving BCG was enormous.

Dr. Brown:
Yeah, I think it’s actually a great point, Bryan. When we look at trying to account for or quantify the variables that go into management of patients with high risk, superficial disease, prior exposure to vesicle therapies, quality of the TUR, surveillance cystoscopies, upper tract evaluations, those kinds of things, we’ll walk through the data a little bit here, but those become real operational challenges over a large organization. Right? So whether it be 10, 15, 100 urologists, trying to have everybody rowing in the same direction really is something that’s going to be important going forward here. Gene, do you have any thoughts on how we can achieve some of those kind of more standardized pathways of care, one, and two, how we might be looking for these patients in our practices going forward now that we have the potential of really new novel therapeutics?

Dr. Cone:
Yeah, absolutely. So, I think that the advanced prostate cancer clinics are a great comparator to look at. I think that you need to have centralized processing, some bladder cancer champions who are really involved in the space, understand all the data, and this is a different space in advanced prostate cancer because with advanced prostate cancer, you don’t worry about the quality of a biopsy or the quality of a diagnosis. With bladder cancer, the quality of the initial TUR really matters and can set the stage for the patient’s clinical journey going forward. So one of the things that I think is probably going to become pretty imperative in this space is that one of the bladder cancer champions does a cystoscopy after the TUR, whether it’s four weeks or six weeks later, to make sure that it really was a complete resection of high quality before you initiate some of these very expensive therapeutics.

Dr. Mehlhaff:
We also have to clean up a little bit of the pathologic reads on those two RBTs. Did you tell me was muscle present or not? Did you tell me, yeah, it’s a high-grade tumor, but did you also mention the CIS or not? I think we’re going to have to drive our pathologists to do a better job.

Dr. Cone:
Yeah. And I think the presence or absence of CIS is something that we started really discussing with our pathologists about a year ago because all of a sudden it was impacting their therapeutic options. And previously we saw that they were very rarely calling CIS unless it was the only pathology that was present. And now I think they’re doing a better job about calling T1 with CIS, TA with CIS, but it’s still a battle.

Dr. Brown:
Yeah, I think having them really look for that CIS patient population is going to be important here. You talk about patient ID and we talk about trying to prospectively identify these folks and risk stratify them effectively. Are we at a point where, or will we be at a point in not too distant future where we may be able to more personalize therapeutic choices for these patients, where based on either tumor-driven characteristics or based on genetic testing or a variety of different endpoints that we can look at that we’re able to say, look, we might be considering X versus Y therapy either in the de novo setting of high-risk non-muscle invasive disease or the BCG refractory setting. Any thoughts about that, Gene?

Dr. Cone:
Yeah, I think that a lot of it is going to depend on the publications for some of the upcoming therapeutics and what they’re allowed to say in the publications about substratification of response for TA and T1 and CIS. And I know that’s an area that there’s some back and forth from a regulatory standpoint about what type of sub-analyses they’re allowed to do. But for a practicing urologist, that would be the single most helpful data to have at top value because that way if you’re not doing more advanced testing, any urologist can stratify into those categories. And then I think as FGFR testing becomes more common, RB testing, we’ll have more and more data points to hopefully put the patient in the right basket.

Dr. Brown:
So when you say you’re talking about papillary versus CIS components versus FGFR positive versus negative patients in the intermediate or other patient populations, right, might help us.

Dr. Cone:
Yes. Yeah.

Dr. Pieczonka:
I think the way this is headed is different than prostate cancer because in prostate cancer, the truth be known is we really don’t have any precision-guided therapy. We think we do, but PARP therapy is probably the closest we have to it, and that’s not really precision-guided and I think there’s going to be an opportunity in the next couple of years if the data bears out to really have something precision-guided like the LUG people do. They have, you look at their box in their toolbox and they have, I don’t know, seven or eight different precision-guided therapies and we just don’t have that quite yet.