Webinar: Treating Non-Muscle Invasive Bladder Cancer by Risk Level

February 18, 2026

Description: A patient-focused conversation with Dr. Katie Murray about how doctors determine the best treatment options for non–muscle invasive bladder cancer. She explains risk stratification in simple terms and talk about current treatments for BCG-unresponsive disease, as well as clinical trials offering hope for the future.

Year: 2026

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Full Transcript of Webinar: Treating Non-Muscle Invasive Bladder Cancer by Risk Level

Patricia Rios:  

And I want to welcome you to the Bladder Cancer Advocacy Patient Inside Webinar Series. My name is Patricia Rios, Director of Education Advocacy, and your host for today’s webinar on Treating Non-Muscle Invasive Bladder Cancer by Risk Level.

Bladder Cancer Risk Stratification categorizes non-muscle invasive bladder cancer or NMIBC into low, intermediate, and high risk groups. Today, our guest speaker, Dr. Murray, is going to explain how doctors use risk stratification to guide treatment decisions for non-muscle invasive bladder cancer. Dr. Murray is currently a professor in the Department of Urology at NYU Langone Health and Grossman School of Medicine. She also serves as the chief of urology services at NYC HHC Bellevue Hospital. Dr. Murray received her undergraduate degree from Westminster College, followed by medical school at A.T. Still University. She completed her residency in urology at the University of Kansas, followed by a Society of Urological Oncology Fellowship at Memorial Sloan Kettering Cancer Center in New York City. Dr. Murray has published over 80 peer-reviewed journal articles as well as book chapters, and we are thrilled to have her here today to cover such an important topic. And with that, I’m going to hand over the screen to Dr. Murray to start her presentation.

Dr. Katie Murray:

Thank you so much, Patricia, and thank you, Allison, and thank you everybody for being here. And special thanks to BCAN actually for sponsoring this and putting together such a cool group of people to talk about something that’s so near and dear to our hearts with bladder cancer. Treating non-muscle invasive bladder cancer by risk level and risk stratification.

Dr. Katie Murray:

Here are my disclosures.

Dr. Katie Murray:

Let’s start where it’s easy, meaning you have a diagnosis of bladder cancer. And the very first thing that becomes important for us to recognize as patients and physicians is this muscle invasive bladder cancer or non-muscle invasive bladder cancer? What does that mean? The bladder has multiple layers starting from the inside out. And the differentiating factor in oftentimes how we treat bladder cancer determines if patients have this, is it invading into the muscle wall layer or is it not?

And so tonight we’re really focusing on those patients in that group of people with NMIBC, which is the majority of bladder cancers. Over 70% of bladder cancers are diagnosed in this non-muscle invasive bladder cancer setting. You see this schematic here. And so essentially we’re talking about those that have this carcinoma in situ where the cancer cells are just on the inside lining, the urothelial lining of the bladder, tumor stage A, and tumor Stage I. You can see there that muscle layer, the lighter pink layer is the tumor Stage II into the muscle. We’re not going to talk about T2 or T3 disease from a bladder cancer standpoint.

Dr. Katie Murray:

How do you get a risk level assigned? This is really important. When somebody has a new diagnosis of bladder cancer, the very most important thing I tell people, or I guess the very first is it cancer or is it not? The unfortunate answer is yes, we’re dealing with a bladder cancer. The second question is it invasive into the muscle or not? Okay. Tonight we’re talking about that that’s not invasive into the muscle. The next thing that becomes very important to us is what is the grade of the cancer? You have these irregular looking cells, the cancerous cells that the pathologist sees in the specimen under the microscope. And we say, “How ugly do they look? Are they low grade cancer or are they high grade cancer?” And then the question after grading becomes, what is the stage of the cancer? Is it that carcinoma in situ or that CIS, is it tumor stage A or is it tumor Stage I? And that is where those things come into high importance and then we are allowed to risk stratify.

A few other things that come into play when we think about risk stratification is the size of a tumor within a person’s bladder, the number of tumors. Is it just one single tumor or was there a tumor in several locations? And the timing, meaning is this a cancer that has happened in the past and we’re unfortunately dealing with a recurrence? And if we are dealing with a recurrence, in what kind of timeframe did that happen? Really this chart is kind of the real meat of non-muscle invasive bladder cancer. This is the AUA’s risk stratification for NMIBC. And so what’s really important, even when I think about teaching students or patients or even my trainees and residents, I say, “If you put your eyes and you realize what comprises patients with low risk disease and you understand what comprises those with high risk disease, the rest of the people fall in the middle.”

If we quickly think about that, low risk disease are these first time patients with low grade tumors that are small, less than three centimeters, a single tumor less than three centimeters. Intermediate risk is a patient who’s had a history, unfortunately, has had a low grade TA tumor in the past, and now they have had a recurrence of that tumor within a year, a single low grade tumor that’s larger than three centimeters, a bladder that has several or multifocal tumors that are low grade, or a small high grade tumor stage A tumor. And then finally, that high risk population, any patients with a high grade tumor Stage I, that would be one less than that muscle invasive. Any patient with recurrent high grade TA disease, large high grade TA tumors in any patient who’s had BCG in the past and ends up with a high grade recurrence, any patient with carcinoma in situ, and then some other more rare that we won’t really get into, but variant histology, lymphovascular invasion of the tumor, or involvement of the prostatic urethra at the time of biopsy.

Dr. Katie Murray:

And so why is risk stratification actually really important for us to understand or what does that actually mean? I’m very cautious when I think about this in very forward-thinking when I’m treating patients and I say, “This patient has a low risk non-muscle invasive bladder cancer or an intermediate risk non-muscle invasive bladder cancer because they had a tumor greater than three centimeters or because they had a recurrence within one year.” To kind of give me a reminder of why they fell in that categorization. But why is the categorization really important? It’s because it impacts what we do, meaning its determination of the risk is determining our risk of recurrence. How likely is it this cancer is going to come back? And then the risk of progression. We’re dealing with a non-muscle invasive bladder tumor. What’s the risk that it becomes a more invasive, such as muscle invasive or T2 bladder cancer, or even further than that, that it becomes metastatic bladder cancer, bladder cancer that is spread outside the bladder into lymph nodes or just some other location.

And determining that risk of progression and recurrence really allows us to say, how aggressive do we need to be in treating this person or this disease? And then with that treatment, how closely do we need to watch them? How often do we need to be surveilling this bladder because of that risk of recurrence or progression? And that’s usually via cystoscopy. I put on here CT scan also can be done occasionally with ultrasounds or MRIs at the same time.

Dr. Katie Murray:

What does that chart look like? If we just break this down into low, intermediate, and high risk, and remember this is all comers, so this doesn’t necessarily mean you, but we look at the five-year risk of ending up with recurrent disease and the five-year risk of ending up with progressive disease into metastatic or muscle-invasive bladder cancer.

You can see here right off the bat that obviously one of our biggest concerns when we’re dealing with non-muscle invasive bladder cancer is the risk of recurrence. That risk of recurrence goes up between low, intermediate to high risk. You can almost say 40, 60, close to 80% as a quick reminder for that five-year recurrence risk. That five-year progression risk, you can see here why we are much more worried about the watching closely potentially in patients with high-risk disease and the risk of progression versus, for example, low-risk disease. We’re talking 5% or less, and then as high as 40% in those patients with very high-risk non-muscle invasive bladder cancer. These numbers are the reason that we may be more aggressive with giving people intravesical therapies in the bladder, such as BCG or chemotherapies or newer agents that we talk about, but it also might be the reason that we may do a cystoscopy more often, of course, in a patient with high-risk disease versus a patient with low-risk disease.

Dr. Katie Murray:

Very familiar with this is the first step in actually determining the risk stratification of a bladder tumor is a transurethral resection of bladder tumor. And surgeons call this or urologist, we call it a little bit different for all of us. Some will call it a transurethral secondary bladder tumor. You may hear people call it a TURB, then you may hear them call it a TURBT. Some may call it a TURBT. And so differing ways, surgeons may describe it as shaving off or scraping off a tumor on the inside lining of the bladder. And then the other thing that’s of utmost importance in patients is that to get a true diagnosis, it does require a TURBT, and that’s under a general anesthetic.

Dr. Katie Murray:

Let’s look a little bit closer at that low-risk disease. Again, if we quickly think about this, this is first-time patients with low-grade TA, small tumors, single tumors. What is the treatment for that? The treatment recommendations based on the AUA guidelines is the patient undergo a resection of that bladder tumor, and they may be offered a single administration of a postoperative chemotherapy at the time of TURBT. The studies say that that’s within the first 24 hours. The most common time that happens is we take a patient to the operating room, we remove the tumor with a TURBT. And in the recovery room, when they wake up, you have a catheter in your bladder and you’re getting a single dose installation of a Gemcitabine or Mitomycin C.

And what is the reason for that? It’s to reduce a relative risk reduction of recurrence of about 35%. What does that mean in real person terms? It means we can decrease the risk of recurrence, which if you remember, it was that 30 to 40% risk of recurrence at five years. We can reduce that up to 15% at four years. In theory, really kind of cutting down that risk of recurrence if we give this single postoperative dose of chemotherapy. This is different than what we’re going to talk about moving forward here as we talk about induction therapy. That is more of a six-dose course of a chemotherapy or an intravesical therapy. And then these people, of course, need ongoing follow-up.

Dr. Katie Murray:

What does that follow-up look like for this low-risk population? Of course, you have the TURBT, we give the chemotherapy, you come back to see me in my office and we’re talking about, “Hey, bad news, this came back as cancer. Good news is that it came back as a low grade small tumor that falls in this low risk categorization. And our biggest concern is the risk of recurrence, so because of that, we’re going to keep an eye on your bladder with ongoing cystoscopies.” The recommendation is to do a cystoscopy in the first three months in follow-up after that initial TURBT. If that cystoscopy is negative for a recurrence, then the guidelines would recommend that we repeat that at six to nine months down the road.

My personal preference is, as I often do that at that nine-month timeframe, that gets us to a solid 12 months or gets us on this yearly plan. And so if it’s negative at that year, then the recommendation is the patient have a yearly cystoscopy for five years in follow-up. After five years without any evidence of recurrence, then it really is a discussion between the provider and the patient or shared decision-making upon the need of ongoing cystoscopy. Things that might play into that shared decision-making is tolerability of a cystoscopy. Smoking being a big risk factor for bladder cancer. Is the patient still smoking? That may increase the risk. And so really drive that need for ongoing follow-up beyond five years. Is there a family history? Was this tumor found because of blood in the urine or was it found incidentally on a scan for some other reason? And that may influence how long you want to do those ongoing cystoscopies.

Of course, at any point in time a patient has a recurrence, then they would switch to the intermediate risk categorization. If you have a history of low grade, you were in this low risk

categorization and one of these repeat cystoscopies shows a recurrence of low-grade disease, we kind of start fresh and you get re-risk stratified at that point in time and make the determination of what the treatment is for follow-up from there. And then the other thing that’s important from a surveillance or a follow-up standpoint, anytime a recurrence happens, the clock restarts. You’d have that follow-up cystoscopy in three months, if negative, following up from there, and then yearly five years thereafter. One thing that is important for this is there’s no recommendations for patients to have upper tract or evaluation of their kidneys or ureters in those patients that fall in the low risk categorization.

Dr. Katie Murray:

Let’s move on to intermediate risk. A lot of patients fall in this intermediate risk categorization, estimates of over 50% of patients with NMIBC will fall in this intermediate risk categorization. A reminder of what that is, patients with recurrent low-grade TA disease, so that low-risk patient that had a recurrence, big low-grade TA tumors, greater than three centimeters, multiple low-grade TA tumors, or those smaller single focus of a high-grade TA tumor. And so what’s important really, if you remember back of what we talked about, that risk of recurrence was quoted at about 50 to 60% in this risk categorization, the risk of progression of around 5 to 7% in this patient group. And so because those numbers are a bit higher than our low-risk population, we do talk about being a bit more aggressive in this population. Our guidelines would tell us that we should consider, meaning have a discussion with the patient and consider utilizing induction therapy, whether that be with BCG or an intravesical chemotherapy pending the risk.

Dr. Katie Murray:

Now, reminder that I put in here, and this is where intermediate risk can be a little bit difficult or a little bit confusing, is that if you look here, the first three of this intermediate risk categorization are patients with low-grade tumors. The last one in the AUA guidelines really does include this mixed bag of patients with small first-time occurrence of high-grade TA tumors. Remember, the intermediate risk is a mixed bag. And so there might be a scenario where the patient falls in the intermediate risk categorization via AUA guidelines, but they had a high grade tumor, a tumor stage A, and that the recommendation may be for that patient because they had high grade disease to undergo induction BCG therapy. Very rarely, especially in today’s world with the BCG shortage, are we utilizing BCG induction or maintenance on patients with these other categorizations of intermediate risk, i.e. these patients with low grade intermediate risk diseases, our first three bullet points here.

Dr. Katie Murray:

And so what I wanted to do in this presentation is really break it down group by group and talk about these risk stratifications and what have we done historically, what the options are, and then what we’re looking at in today’s world and it’s 2026 in this really new exploding world of bladder cancer. For the first time, we do have an FDA approved agent for a subset of patients with intermediate risk non-muscle invasive bladder cancer. That newly approved agent is Intravesical Mitomycin Reverse Thermal Hydrogel technology, or known by the trade name of Zusduri. What is that? It’s a once weekly installation for six weeks of a chemotherapeutic.

Now, interestingly, this does not have to be after a patient has a TURBT or a biopsy. It was FDA approved as a primary treatment for patients with recurrent low-grade TA disease. That first bullet point of what puts patients in an intermediate risk categorization, recurrent low-grade disease, if they have that cystoscopy in the office and recognize a recurrence, they could go to the operating room for a repeat TURBT or can use this Intravesical Mitomycin Hydrogel as a primary treatment induction course once a week for six weeks.

What were the results of the trial that got Zusduri approved by the FDA? And it was based upon complete response so a patient had this therapy after being considered in the intermediate risk categorization, and they had a follow-up cystoscopy at three months, and 78% of patients had a complete response, and so had no tumor remaining at three months. 79% of those patients remained free of recurrence at 12 months, and 70% of those patients were deemed free of tumor at a follow-up of two years. Now, if we remember back in our minds, the risk of recurrence over that four to five-year timeframe is around 50 to 60% for this patient population.

Dr. Katie Murray:

Whether patients we decide to proceed with a Zusduri treatment or another intravesical or ongoing surveillance, the important thing is that I tell my patients, “You’re never free of me,” meaning we get to be friends and we have to closely watch inside the bladder.

Intermediate risk is a little bit closer follow-up. And so these patients are seen with a cystoscopy in the office every three to six months for two years, every 6 to 12 months during year three and year four, and then yearly thereafter. And then a reminder that anytime there’s a recurrence, the clock resets. It goes back to square one. And then the other thing that’s recommended for patients with intermediate risk or often considered recurrent low grade TA tumors that upper tract evaluation or evaluation on CT scan or MR urogram, looking at the kidneys and the ureters should be done every 12 to 24 months or every one to two years.

Dr. Katie Murray:

All right, let’s really dive in here, time is flying, and really talk about high risk disease. There’s a big chunk of people that fall into this high risk categorization, unfortunately, and it is where the mainstay of our BCG therapy and our ongoing new approvals for patients. In patients with high risk disease, who are these patients? Again, as a reminder, high grade tumor Stage I, big high grade tumor stage A tumors, patients with multiple high grade TA tumors, patients who have a recurrence of high grade tumor, and those patients with carcinoma in situ. Our guidelines say that you should administer a six-week course of induction BCG therapy for these patients. Now, if we remember back, this is a little bit of vocabulary, but in our intermediate risk categorization, it said clinician and patients could consider utilizing an induction course of chemo or BCG, but in high risk stratification in NMIBC, it is clinicians should administer six-week course of induction BCG therapy.

The original guidelines say when patients have a response or if it responds to intravesical BCG therapy, they should have continual ongoing maintenance therapy based upon the availability of BCG for up to three years. Now, as many of you out here recognize and have read about or your physicians have told you, we’ve been in an era where we’ve definitely had this crunch of availability of BCG therapy, and so many of our guidelines have actually kind of condensed that down and said in patients who respond well to induction course chemotherapy should have one year of maintenance therapy in follow-up.

Dr. Katie Murray:

When we think about this, I think it’s super important to look at new data and things that are coming out there. BCG, when it works, it can work quite well for patients. It’s been the mainstay of high-grade non-muscle-invasive bladder cancer for many, many years.

And so what has happened over the past several years is we’ve asked ourselves the question, and patients have asked us this question, is BCG can work, but can we make it better? Can we make it better for high-risk patients for NMIBC? I have three trials listed here that have been hot in the news and recently of trying or attempting to do just that, make BCG better than what it already works. And so the first one is the Crest trial. It is a trial that basically, if you think about it in quick terms, it compared patients getting induction and one year of maintenance BCG plus Sasanlimab, which is a subcutaneous anti-PD-1 injection versus BCG therapy induction and maintenance on its own and followed these patients and out to 36 months.

They did see that there was an improvement in event-free survival, so recurrence-free survival or overall survival. 82% of patients who had this combination therapy had no recurrence versus 75% of patients had no events who had BCG induction and maintenance alone. Now, the other thing that’s very important to recognize is obviously we see here that 7% difference, but when we think of any therapy and especially a new therapy, we have to say, “Okay, there’s an advantage, but at what risk does that come at?” And so if we look at the grade three, which are the first serious adverse reactions, the adverse reaction of grade threes were 29% in those patients who had the addition of Sasanlimab versus 6%. I’m going to talk the same way through these remaining two trials.

The Potomac trial was induction in maintenance BCG plus Durvalumab versus BCG alone. Again, quite similar results at 36 months, 82% versus 77%, quite similar in our adverse reactions of 21% versus 4%. And then the last trial being the Albans trial, induction and maintenance BCG plus Atezolizumab or Tecentriq versus BCG induction and maintenance alone. And there was no difference in this trial in event-free survival or high grade recurrence-free survival. And we can see here the grade three adverse reactions in this population.

Dr. Katie Murray:

High risk we’ve kind of talked about and because of that risk of not just recurrence, but that risk of progression in this patient population, our surveillance protocol is a bit more stringent. And so patients who fall in that high risk categorization should have a cystoscopy every three to four months for two full years, and then every six months during year three and year four, and then yearly thereafter, and then a CT or MR urography every year to two years again in this patient population.

And so it’s very common for patients to go through this.

Dr. Katie Murray:

And a big thing that we talk about in today’s world is BCG unresponsive disease. We just looked at these newer updated numbers from these trials that were comparing against induction and maintenance BCG for one year and saw that the risk of recurrence or the event-free survival of BCG alone was about 75 to 77%. But what does that tell us? That tells us that there are a group of people that BCG, that the cancer just does not respond to BCG. What does that mean? And so BCG unresponsive cancer has become really a term that we use often. And so patients may see in your clinical notes or in your chart, BCG unresponsive carcinoma in situ or BCG unresponsive non-muscle invasive bladder cancer. And so this is essentially these patients that have a recurrence of high grade T1 within three months after BCG, you can see here TA or T1 less than or equal to six months after the completion of BCG therapy, or carcinoma in situ less than equal to 12 months after BCG therapy.

Dr. Katie Murray:

What now? You’ve had BCG followed the guidelines. Unfortunately, we didn’t fall in that categorization and BCG didn’t work for my cancer. I tried really hard to… I wanted it to work. And so the first thing that your surgeon’s going to talk to you about, a urologist is going to say, “I have a really good cure for that and it’s guideline recommended. And that would be to do a radical cystectomy and take a person’s bladder out.”

Dr. Katie Murray:

Of course, our patient centeredness says we’re looking for something else and looking for something more. But essentially, I couldn’t do this presentation without bringing up the impact of cystectomy versus these ongoing intravesical therapies in patients with BCG unresponsive disease, basically looking at patient reported outcomes in patients who have had their bladder removed versus their bladder staying intact

Dr. Katie Murray:

Called the CISTO trial as we see here.

Dr. Katie Murray:

And what we did identify in this trial, which I think is important in looking at these group of patients with carcinoma and CIS is

Dr. Katie Murray:

that quality of life, overall physical functioning and some things can favor radical cystectomy, bladder sparing, bowel health, sexual health, overall functioning, progression seat-free survival favored that bladder sparing. I throw that out there and then no difference in patients with overall physical functioning, physical functioning by age, urinary health, cancer-specific survival, or overall survival. Radical cystectomy is a very reasonable option and guideline-based for patients with BCG unresponsive cancer.

Dr. Katie Murray:

But what have we recognized over time is that our patients have come to us and said, “Okay, Dr. Murray, that is fine. I realize that that is a definitive way to remove my bladder, but I don’t want that. I want to keep my bladder. What can I do to keep my bladder?” And so I have listed here, and we’re going to spend a few minutes talking about each of these, and then I’m happy to, again, take questions towards the end, but quickly run through the agents for doing just that, keeping your bladder. Pembrolizumab, the first approved Nadofarogene, N-803 plus BCG, TAR-200, the Gemcitabine drug delivery device, those four options are all FDA approved, and then retrospective studies of utilization of intravesical Gemcitabine-Docetaxel chemotherapies.

Dr. Katie Murray:

And so we see here these are going to be shared, so I’m not going to go through this because we’re going to go through each of these a little bit fairly quickly individually, but we can see here these are all fairly new therapies. And so the long-term complete response is not here for all of the therapies, but something that I think is important and very patient-centered is that bottom line of looking on cystectomy-free rates. The incidence of patients being on these therapies and continuing to keep their bladder intact, which is what people desire.

Dr. Katie Murray:

Let’s quickly start here. Pembrolizumab is PD-1. It’s the first FDA-approved agent, but not highly utilized due to adverse reactions and a low complete response with around 19% complete response compared to other agents. That five-year data shows about 10% complete response at five years. And there definitely can be some benefits of this in that it isn’t systemic IV therapy, so it doesn’t require a patient to hold their bladder if there’s any issues with catheterizations or specific reasons that make giving therapies in the bladder more difficult. Pembrolizumab could be an option for patients.

Dr. Katie Murray:

How about Nadofarogene? Nadofarogene firadenovac is a non-replicating recombinant adenoviral vector that copies this interferon alpha-2B gene into the cancer cells. It’s the second agent that was approved for BCG unresponsive carcinoma in situ. It’s very tolerable. It’s given once every three months to an intact bladder, of course. Patients must hold that in their bladder. It does have a higher complete response at one year at about 25 to 44% for CIS versus papillary disease, but it has attrition just like these other patients, but at five years, over 71% of patients have their bladder intact still on the inside of their body.

Dr. Katie Murray:

N-803 is the third agent that’s approved or third agent that was approved by the FDA that has even a higher complete response rate at one year with a bit less attrition. There’s some goods and bads here.

And that is good, is extremely familiar to urology clinics because it is co-administered along with BCG and urology clinics are quite familiar and patients are familiar with the dosing regimen and schedule of BCG and have extensive experience with that. But the downside of that is that it has to be given along with BCG. And we do live in an era where sometimes the attaining BCG can be complicated for patients or for practices in general in being able to do that.

Dr. Katie Murray:

With the fourth then approved agent by the FDA, the most recently approved in the last four or five months is TAR-200 or Inlexzo. And basically it’s the fourth approved agent, has a high complete response rate, has some durability, but like many of the others, it has some attrition and continues to wane over time. They do have a randomized controlled trial that’s completed for papillary disease. A big advantage of this is that patients, this is administered. It is a chemotherapy, it’s administered in a urology office, so it’s quite familiar from a side effect profile to urologists, but it doesn’t require any compounding or chemotherapeutics, but it is a device that’s inserted into the bladder. It’s a drug eluding “pretzel,” as you can see here, the size of that a little bit bigger than the size of a quarter, maybe a half dollar size here in the United States that we would be familiar with.

And it is a device that goes in the bladder. It is not permanent. It has to be removed every three weeks. That is a removal of the device with a cystoscopy and a replacement of the device with a catheter every three weeks for six months, and then every three months for an additional six doses, about a 13% grade three or grade four adverse reaction.

Dr. Katie Murray:

And so when we think about this, time flies and there’s so many things to talk about and so much excitement, but I think what’s really important for us to recognize as urologists and for you all out there to recognize as patients and caregivers and people that are dealing with loved ones and family members with bladder cancer is that we have options now. We’re doing the very best that we can at present time, but essentially in today’s world, our current paradigm is BCG. And if that does not work for the cancer or the cancer outsmarts it, we move on to second line or third line therapies in clinical trial, and then a patient has to go on to radical cystectomy.

What do we hope for in the future or what is our near future paradigm as we look at these new agents that’s been approved, that we utilize BCG or BCG, some alternative to BCG,

essentially a frontline therapy, whether that be BCG or an intravesical chemotherapy. And if the cancer doesn’t respond to that, we have options for second line, potentially third line and fourth line therapies, and really kind of kick that can down the road of requiring a radical cystectomy. Now, what’s extremely important for me to bring up here is that I just listed out four agents that have been FDA approved in the last five years for BCG unresponsive non-muscle invasive bladder cancer. But questions that we don’t know is how well these agents might work before or after one another, how they would be potentially sequenced in different patients, which one should come first or which one should come second.

And we never want to lose that window of opportunity for cure, meaning part of the reason we do all of the aggressive things we do for patients with high-risk disease is because of that risk of recurrence in 60% of people, but also because there is that risk of progression of over up to 10, 20, in some reports, even up to 30 or 40% of patients have progression of disease with high-risk disease. And we do not want to be doing therapies inside the bladder and lose an opportunity to cure someone of bladder cancer and miss that opportunity to do that because we’re trying to spare the bladder. Finding that fine line between sequencing these newly approved therapies and learning how to sequence them for different patients is our new future paradigm. I think this is what many of us are using in today’s practice because we do have more than one option now in BCG unresponsive disease.

But really to get to these futures, like I said, we have to limit toxicities, we have to not lose that curative window, limit progression, and then really limit recurrence at the same time. What’s our real hope and desire when we look at this is this extended future paradigm, I’ll give thanks to Max for providing this slide, but is that we might be able to predict what patient is going to respond most appropriately to an intravesical immunotherapy such as BCG or may need BCG plus an additional immunotherapy as in the BCG-naive setting or patients that may respond better to one of these antiviral immunotherapies or an intravesical chemotherapy. We might be able to say, “Okay, the patient in front of me right now, we have a biomarker that predicts you should have therapy A, B, C or D, or these therapies are not going to be beneficial and we should think about doing an early cystectomy or removing the bladder.” And then the desire is that that really reduces our risk of recurrences and our need for these ongoing salvage therapies, that there’s a different personalized medicine therapy for each of our patients.

This is not even come close to approaching everything that we want to approach for or get to here as we think about non-muscle invasive bladder cancer, but I hope this really kind of laid a baseline as to why when you’re in your friend group and you’re out to dinner and you have friends with bladder cancer, why one person might get an intravesical chemotherapy and somebody else might end up with an intravesical BCG therapy or an induction and maintenance and ongoing therapies.

Dr. Katie Murray:

And so this is not by any means conclusive, but it’s really just an idea of kind of looking ahead of how many new things are coming out, really looking at this personalized therapy and what we can do

Dr. Katie Murray:

next over the years to come for patients with non-muscle invasive bladder cancer, because that’s what we owe to you guys.

Patricia Rios:

So there’s a question in the chat about the EAU risk stratification. Could you talk about what that is and if they vary at all, and what are your thoughts around the EAU guidelines?

Dr. Katie Murray:

Yeah. I think that’s an excellent question. Obviously, we have limited time, and so we didn’t go into that, but it’s a discussion that we have in the urology world all the time. And so one of the most important things, I think, at least in my mind, one difference in the EAU guidelines is that all patients with high grade tumor fall in a high risk categorization. And that’s a little bit different than the AUA where we have those first time small high grade TA tumors that fall in that intermediate risk categorization. That’s one big difference. And then the other thing that I think is important to recognize in the EAU guidelines is they do substratify the high risk population into a very high risk population. And so that can be patients who have a variant histology. A traditional bladder cancer is urothelial cell carcinoma, but they may have a component of another type.

And sometimes we start talking about cell types, we talk about squamous cell carcinoma, we can talk about a micropapillary variant and some of these other variant histologies. And really that is based upon our worry and our risk of progression of disease in that patient population. It’s a group of patients that we might worry a bit more and might fall on the higher side of that risk of progression from that. That also accounts, if you think about the AUA guidelines, you’ve noticed in many of these follow-ups and these surveillances, it gives a little bit of wiggle room. It might say for the first year or the first two years, the cystoscopy is every three to six months, or in the high risk it was every three to four months. And so it allows a little bit for that wiggle room and that patient physician discussion of what that is, meaning if you have a variant histology, we might watch you a little bit make sure we do that every three months instead of the every four months from that situation. They’re very similar with a few minute differences.

Patricia Rios:

Great. Thank you for explaining that. Cystoscopies continue to be sort of the gold standard and patients are wondering, are there any sort of replacements for that, especially for follow-up, particularly as it relates to urine biomarkers? Any thoughts on that?

Dr. Katie Murray:

Yeah, so it seems like a dream world, and that the answer to that should be magically yes. Urine is such a great way, and it’s so easy to attain in our clinic. Unfortunately, at present time, there’s many biomarkers in exploration, and there’s some companies out there, and your physician may actually even utilize some in practice, but a majority of times they’re still being utilized all in adjunct to cystoscopy. Nothing has had enough sensitivity and specificity to say, “You don’t have to have a cystoscopy anymore, and we trust this urine-based test to say, yes, you have a recurrence, or no, you don’t have a recurrence.” A majority of them in today’s world all use as adjunct. I would like to say that that’s my future dream world, is that I don’t have to do all these surveillance cystoscopies, but the evidence just isn’t there yet.

Patricia Rios:

Thank you. I think that’s a hope and dream for all of us.

Dr. Katie Murray:

That’s right.

Patricia Rios:

Speaking of test, we have a question relating to the MRI urogram versus the CT urogram. Is one more sensitive than the other?

Dr. Katie Murray:

Yeah. No, I think as long as you’re getting one of those scans, and part of it becomes a little bit of your own institution or your own practice, because there are differences in CT machines and MR machines across different practices and how sensitive or specific that they might be or how well they can image. Probably more important than saying which one you’re going to get is really staying consistent, meaning if you’ve done CT scans, continuing that CT scan so we can always compare back to the past is more important than one being better than another.

Patricia Rios:

That’s helpful. Okay. Now related to BCG and the shortages, how do you select how or which patients will get versus something else?

Dr. Katie Murray:

Yeah, so I think that’s a huge challenge. And I’ve talked to so many of my friends in how we do this. And I think it is where we just talked about the European guidelines versus the AUA guidelines, and it does give this ultimate even higher risk. And so my real goal is to be able to get induction BCG in every single patient who falls in that high risk categorization and I think that’s the highest risk of recurrence and the highest risk of progression. And then the evidence for the ongoing maintenance therapy is not quite as strong as the induction therapy. Getting that induction in has been prioritized at our practice over the ongoing maintenance, which is also why that maintenance schedule has been kind of condensed down to that one-year timeframe in many, many practices from that standpoint.

But I didn’t even have time tonight and I thought about doing it, but talking about trials that are going head-to-head against BCG that are not based upon BCG. I talked about the three trials that combined a PD therapy along with BCG, but for example, the ongoing or the now closed, but waiting for results of the BRIDGE trial, which is comparing BCG to an intravesical chemotherapy such as intravesical Gemcitabine-Docetaxel to say, “If we don’t have BCG, which has been the standard forever, can we use an intravesical chemotherapy and are the results as good or could they be better?”

Patricia Rios:

That kind of goes well with the second question then. I don’t know if the information is available. There is a question about GemDoce as a second-line therapy compared to the newly approved second-line treatments that you mentioned, particularly for intermediate risk. Do we have any information about that?

Dr. Katie Murray:

Yeah, so it’s really comparing a little bit of apples and oranges. And so what we don’t have in any of these trials is we don’t have any evidence where we said, “Okay, we took all of these patients and we said, ‘You get this one, you get this one and you get this one.'” And we’re not supposed to say, “Okay, we did this trial and this was the results of this drug, this was the results of this one, this was the results of this one,” and try to pick what’s best. The simple answer is no, we don’t have that answer, but we’re humans, and so it’s hard for us to not look at those numbers. The one thing that often gets brought up about intravesical Gemcitabine-Docetaxel, which is widely utilized across the United States, especially in academic urology practices as a second line to BCG therapy is it’s been tried and true.

We’ve used intravesical chemotherapies for quite some time after BCG therapy, but all of the results with intravesical or majority of the results we have with intravesical chemotherapy is based upon our own experiences and reporting on that retrospectively, meaning treating a bunch of patients and then looking back and seeing what the results have been of that GemDoce. Again, I mentioned already once, but the BRIDGE trial is a very exciting trial that we’ll read out, but not until another year or so, but it compared patients new bladder cancer, high-grade disease either got intravesical chemotherapy with the GemDoce or intravesical BCG therapy. We’re really excited about that as a urology community.

Patricia Rios:

Yes, we’ll be excited to hear what those results say.

Dr. Katie Murray:

Yes.

Patricia Rios:

There was a question about biomarkers earlier on, but do you mind explaining what biomarkers are? What are they looking for? Is it the tumor itself, the urine, the blood? What is, I guess, the biomarkers?

Dr. Katie Murray:

Sure. I think a biomarker, if you think about it in traditional terms, essentially a biomarker is looking for a cancer, and that can be in any way, shape, or form. And so if we think about it technically, you might say our cystoscopy is a biomarker. Now this is getting really technical because it’s trying to marker out the cancer and say yes or no, there is a cancer. When we identify or we find something, and what we’re looking for in a biomarker is for that biomarker to, if it’s positive to say, there is definitely a cancer in this person, if I test a urine biomarker and it’s positive, then it says, “Katie, there is a cancer there and you have to find it.” If that biomarker is negative, that I would have complete confidence saying, “You do not have cancer. The chances of that are extremely low.” That’s essentially what a biomarker is trying to do.

Patricia Rios:

Great, thank you. There was questions about CIS, C-I-S, and whether the new treatment options that you share, how do they respond to CIS type tumors?

Dr. Katie Murray:

Yeah, so interestingly, and like I said, there’s so short of time, but all of the FDA approved agents, so that would include the Pembrolizumab, Nadofarogene, N-803 plus BCG, and Inlexzo are all very specifically delineated out by the FDA that these are FDA approved for BCG unresponsive carcinoma in situ tumors with or without concomitant papillary disease. The numbers that you look at across the board in that table are those carcinoma in situ population.

Patricia Rios:

Thank you. And so there seems to be a lot of questions in the chat related to GemDoce treatment, and so questions around efficacy, surveillance, cystoscopies. Could you provide more information around that treatment option, particularly as it relates to, I guess, the intermediate risk?

Dr. Katie Murray:

Okay. The important thing, the one thing I will say, and this kind of came up a question, I think I saw it somewhere else in the chat as well, is the reminder that irrelevant of what your schedule is and what therapy you’re undergoing, if that’s BCG or GemDoce or any other of these newer approved FDA agents, that follow-up pattern of the follow-up cystoscopies, CT scans, MR urograms does not change. I often explain it to people is you may be getting your intravesical chemotherapy on this timeline, but you also have this other kind of calendar going of how often you need to have your cystoscopy. Intravesical GemDoce is the retrospective data essentially that is inclusive of an induction course of the two chemotherapies together into the bladder. That’s a six-week induction course, and assuming a complete response, patients would go on a maintenance course of GemDoce, and that’s one single installation in the bladder every single month for 11 additional doses, so for 11 months. And so while that’s happening, so they get six doses and then monthly maintenance.

And then a reminder, you’re getting that monthly maintenance, but you’re also seeing your urologist and not just the nurses or MAs in clinic, and you’re getting a cystoscopy every three to four months per the guidelines. There’s kind of two things happening at once. You’re getting your therapy and you’re getting your surveillance. They may not always coincide on the same day.

Patricia Rios:

Thank you. Gosh, we have so many questions. I’m looking at the clock.

Dr. Katie Murray:

I know. I’m going through as well. I’m like, “Oh my goodness.” Okay.

Patricia Rios:

Thank you, Dr. Murray. Okay. Let’s take this one around full dose for BCG versus half a dose. Is there a difference?

Dr. Katie Murray:

Yep. I don’t have any prospective data that’s ever proven to say full dose versus half and third doses. What we believe is the BCG elicits an immune response. And so eliciting that immune response and having that ongoing dosage with the maintenance BCG is really what’s upmost important. And so based upon that science and the fact that we do have a shortage and we’re trying to get as much BCG to have that ongoing response in patients as possible, many practices are doing half dosing or I should say split dosing in using one vial. And instead of doing the whole entire dose into a single patient, that might be split and using half of the dose. And so half dosing or even quarter dosing, one third dosing in the maintenance regimen that is not very much utilized in the induction course because that induction priming with the immune system with BCG is really the mainstay, that once a week for six weeks, full dose.

Patricia Rios:

Thank you. Well, I’m looking at the time end, so what I want to offer is to our listeners today. Thank you so much for joining us. You have such great questions. And what we’ll try to do is gather these questions and invite Dr. Murray back for another presentation or part two, and we can continue to build that presentation around these questions. What I will say is that also related to, I think there were a lot of questions about when this new plant Merck is opening, so that hopefully will address some of the BCG shortages. And so continue to stay updated with BCAN. We are in communication and we’ll share any updates as we receive them.

With that, Dr. Murray, what I would like to ask, I mean, there was so much information, very rich content today. What would be the takeaway message that you want our listeners to leave with today?

Dr. Katie Murray:

Yeah. Yeah, thanks so much for having me. And I think really it gets very confusing of realizing that risk stratification and why one person might be getting one thing and somebody else is getting something else, but really understanding and trying to ask your provider the question, “What is my risk stratification?” And that’s important for you to know because it tells you your risk of recurrent disease, it tells you your risk of this disease progressing. And then based on those two numbers determines how aggressive you need to be in the treatments that you give and how aggressive you need to be in making sure that you have that follow-up surveillance with those cystoscopies, so with the urologist. I think it’s okay. Ask your surgeon, what is the risk stratification? Because they may not just come out and blanketly say it as simply as, “As you fall in intermediate risk so because of that, I’m going to do this.” They might just say, “You need BCG or I’m going to do this therapy.” And I think it’s okay to ask those questions.

Patricia Rios:

That is an excellent takeaway. Well, thank you so much, Dr. Murray, for joining us today and for the comprehensive presentation. We hope to have you back real soon.