Managing High-Risk NMIBC
Transcript: Navigating NMIBC treatment changes
Roger Li, MD, and Ashish Kamat, MD, MBBS, FACS
Podcast recorded October 2025. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
- [Ashish] Welcome to the podcast series, "Expert voices: Navigating non-muscle-invasive bladder cancer." Today's episode is titled, "The shifting landscape for treatment of non-muscle-invasive bladder cancer." I'm Ashish Kamat, and it's a distinct pleasure to be joined by Dr. Roger Li, who really needs no introduction to anyone who's doing anything in bladder cancer. Welcome, Roger.
- [Roger] Thanks so much, Ashish for having me.
- [Ashish] When it comes to discussing this topic, I can't think of anyone better than you, and in the next 20 minutes or so, we're gonna go through a whirlwind of different options and how we tailor therapies to patients, et cetera, et cetera. But first off, if you wanna enlighten us on generally, what are the things that you are considering when you approach a patient that is sent to you, say in consultation that has potentially BCG unresponsive, non-muscle-invasive bladder cancer?
- [Roger] Yeah, that's a great question. And you know, it's exciting times because we have so many different options at our disposal now for treating this disease space compared to even a few years ago. But you know, in general, I tend to consider the efficacy of the drug obviously, even though we're not supposed to be comparing complete response rates from trial to trial. But in general, I think because of the strict definition for the BCG unresponsive criteria and also how similarly these trials have accrued and also follow their patients, I tend to use the CR rates that have been reported by these large single arm studies as a guide for letting me know what the efficacy rates to expect on these treatment options are. And of course also along with that, the safety profile of the drug. So as we discussed that at IBCG retreat a couple of years ago, even though systemic immune checkpoint blockade has been approved for the space because of the systemic toxicity that's associated with it. You know, in contrast to the modest efficacy, we have to think twice about, you know, whether or not that particular treatment is suitable for some of our patients. And in addition to that also things like the logistics, the financial toxicity that's associated with some of the drugs that are available. So, you know, I really take all of those factors into consideration and finally have a frank conversation with the patient and see what it is that they have preferences towards and understand where they're coming from as well.
- [Ashish] And we'll dig deeper into all of those different aspects because that's clearly, you know, very important when we talk to patients. But first, you know, you talked about the clinical trial design, and of course we sort of recognise that the entry criteria for patients into trials for BCG unresponsive non-muscle-invasive bladder cancer were very strict for a valid reason. And that reason was because we were enrolling patients on a single arm study. And the guidance from regulatory bodies, such as the FDA, was that you could use those single arm studies for registration purposes only if the patients met those very strict entry criteria. But in the real world, Roger, what do you factor in? Do you factor in those very strict criteria for a patient sitting in front of you, or do you offer them a little bit more relaxed criteria? Or on the other hand, is it more strict because clearly you are offering more toxic therapy to the patient. So how do you actually decide clinically if the patient meets these criteria for being BCG unresponsive? And what's your general advice to people listening?
- [Roger] No, that's an excellent point that you bring up. You know, so certainly for the clinical purposes we have to make sure that patients are meeting the BCG unresponsive definition, but you know, in clinical practise, I really think about just whether or not the patients have received adequate BCG in the past and you know, obviously the type of disease recurrence that they had suffered. And, you know, not necessarily taking into account sometimes the length of time that's elapsed since the last time that they were diagnosed with BCG unresponsive disease. I mean, in fact, I think you yourself had led an effort years ago to qualify such patients for the clinical trial purposes as well. And I think the FDA has since adopted that stance that if you were to be one BCG unresponsive, you're always considered to be carrying the disease label, if you will, with you. And such patients are eligible for clinical trial purposes. But I think, you know, there is something to the adequacy of BCG provided as you and I had again conducted a study back when I was in fellowship demonstrating the prognostic implication of receiving adequate BCG with the induction plus the first maintenance course, versus those patients who had developed recurrent soon after the induction course with TA high grade or CIS, that clearly they had different progression-free survivals, they had different cystectomy free survivals, and that their outcomes are clearly drastically different. So, you know, I think even though since then there's also been additional data coming out of MD Anderson looking at patients who were potentially treated with additional BCG after they've received the adequate BCG. But I think in general, you know, the receipt of adequate BCG and then developing high grade recurrence this really puts patients in a category that's different than if they've done high grade recurrence after induction alone. And so I think for those reasons, you know, I really look at whether they received adequate BCG before developing high-grade recurrences to determine whether there'll be fitting of the next line of treatment if you will.
- [Ashish] Yeah, and I think just to summarise, you know, that point is very important because we need to make sure that patients who are labelled as BCG unresponsive and non-muscle-invasive bladder cancer, truly have had an adequate attempt of treatment of BCG, right? Because it's an immune therapy and if it's not given appropriately, you don't allow the immune system to get primed the appropriate immune cells. I mean, you are doing a lot of work in this space on the basic science translational aspect of things, but for our community urologists or those listening in, patients listening even, make sure that they have had an adequate chance to have their tumours respond to immunotherapy. And we know currently the best immunotherapy for bladder cancer or for any cancer really as far as response rates is intravesical BCG for many, many reasons. So I think that's a very important point. And then of course, the real world considerations come in. So, you know, talking about real world, obviously we have to consider cost, we have to consider other institutional characteristics and guidelines. And at a EAU 2025, there's a very interesting session titled "The price of success," right? And that's where the discussion sort of centred a little bit around the use of the elephant in the room, the non-FDA approved off-label use, doublet intravesical chemotherapy, and how that has in many ways become standard of care in at least North America with all these other drugs being studied. So tell me some of the thoughts as far as the practical clinical considerations that you think influence the use of this doublet intravesical chemotherapy with gemcitabine and docetaxel, both in your practise and in, you know, your colleagues that have sent you patients.
- [Roger] Yeah, so in general, I think doublet intravesical gemcitabine and docetaxel is a very effective drug both in the BCG exposed or unresponsive setting as well as, you know, from my limited experience now on the BRIDGE trial, also for the BCG-naive patients. You know, I just think that alike what we do in the muscle-invasive neoadjuvant setting as well as in the metastatic setting, we know that the multiple chemotherapy regimens tend to confer a higher efficacy rate than single agent cisplatin or other types of single age of monotherapy chemotherapy drugs. It just makes sense that when combined, you're gonna be able to get higher efficacy rates because of the different mechanism of action of the different chemotherapeutic agents. And the nice thing is, of course, as you and I know that like you're also able to limit the toxicity within the bladder when treated intravesically, unlike when these agents that are given systemically, you're really looking at compounding the systemic side effects of these drugs. So it's a really nice opportunity for us to use these. And on top of that, I think, you know, the cost component of it is also very important, especially when compared against some of the other alternatives. And so I think certainly Dr. O'Donnell from University of Iowa's pioneer this drug combination and has brought along with other institutions to light a lot of the data in the real world setting use using this drug, which looks, you know, to be honest, very comparable if not even better than some of the prospective trials that we've ran. But, you know, we have to obviously keep in mind that these are retrospective studies with their caveats, but nevertheless, you know, I think it's a regimen that's very familiar to academic urologists. That we have a lot of experience with in dealing with, the side effect profile that sometimes come up. And also the protocol for this intravesical doublet chemotherapy is well worked out in many academic settings. So it's just natural for us to use this as a defacto first line treatment in the BCR responsive setting. And, you know, we'll see what the results show from the BRIDGE trial, but I look forward to maybe it one day becoming an option in a naive setting as well.
- [Ashish] Yeah, and we're gonna have a separate, you know, episode of the series focusing on emerging options in this space. But briefly, and you know, not to put you on the spot, but just very briefly, where do you currently rank this intravesical gem/doce in your discussion paradigm with patients that don't want a radical cystectomy and don't qualify for a clinical trial?
- [Roger] Yeah, so I think because of our familiarity of administering this drug and also because of, you know, the cost component that we take into consideration, we actually use this as the defacto drug of choice for patients who initially developed BCG unresponsive CIS or papillary disease. And certainly, you know, we also make an effort to enrol patients onto exciting clinical trials. But nevertheless, I think we have adopted this truly in the academic setting as a defacto first line or therapy of choice.
- [Ashish] Yeah, and again, you know, you and I have chatted before, but just for our audience, if you could briefly tell us, does the factor of a patient having CIS influence your specific decision to use systemic or local therapy and specifically here we're talking about gem/doce. And also share with us a little bit why you think there has been such an adoption in the academic centres and not so much in the community centres.
- [Roger] Certainly, so I think having CIS components in the recurrent disease, that's a risk factor. And that's been shown time and again in previous trials and also in the latest iterations of the BCG unresponsive trials where you actually see higher efficacy rates. And, you know, keep in mind, you know, just for the audience that the measurement of the response rates in the CIS setting is really looking at complete response because you're always starting off with a disease burden at baseline because the CIS cannot be completely resected. Whereas for the papillary only cohort, you're looking at recurrence free survival rates because the papillary tumours are thought to be completely resected at baseline. So there is a distinction there, but nevertheless, looking at CR rates, along, you know, the one year course after BCG unresponsive disease as well as the recurrence free survival rate between the two groups, we've consistently have seen that multiple agents, including pembro, including atezo, including nadofaragene, and including N-803 have consistently shown that there's higher efficacy rates in the papillary only cohort. And I think, you know, so it's natural because these tumours are macroscopically seen on cystoscopy and they're completely resected so that you tend not to have these recurrences of unseen tumours at the time of the diagnosis. Making papillary only disease sort of a little bit easier to treat if you will. So, but we've also kind of talked about this topic at the retreat a couple of years ago for IBCG, whether or not for papillary only disease, that it's more fitted for a chemo ablative therapy where you can use a chemo ablative agents to completely treat the disease, whereas those immunotherapeutic agents may be better suited for the CIS agents because you're inducing the immune system to act against the disease that's present at baseline and beyond. And you know, we didn't really come to a consensus on that because the bottom line is I just don't think that there is enough data to support that. But nevertheless, you know, through the meta analysis that we've done with the IBCG group and just looking at the data across so many different trials, it's a very consistent theme that if you were to have CIS, the chances of recurrence are higher no matter what type of agent you were to use. So, you know, I do kind of consider that to a certain extent, but nevertheless, I feel like we want to choose the most efficacious agent for all of our patients. And so I think with intravesical gem/doce with the data that's been shown, you know, that's really again, my go-to choice for first line treatment in the BCG unresponsive setting. And then your second question was regarding?
- [Ashish] Why has it been used more in academic centres and not as much in the community?
- [Roger] Yeah, so, you know, my understanding is that it somewhat has to do with the reimbursement of docetaxel in the community setting. And I think that kind of plays into the choice that some community urologists, you know, may make in choosing their agent of choice, but certainly in the academic settings the decision stems from some of the financial implications of the drug choice that we make. So I think, you know, going by the efficacy and going by the costs, to me it's a clear choice that gem/doce is probably the best choice for, at least as now for patients with BCG unresponsive disease.
- [Ashish] So Roger, you know, of course there's emerging drug delivery systems, right? And those that might be able to incorporate chemotherapy into the drug delivery system. Do you think sustained release platforms are going to be something that are gonna change the way you recommend chemotherapy to patients? Do you think that, you know, there's any specific need there that you are anticipating?
- [Roger] Yeah, I think we could only go by what the data shows, and certainly intuitively, I think having a sustained release system will expose the cancer to more chemotherapeutic agents over time. And knowing that chemotherapy works by chemo ablative mechanism, it just stands to reason that such a system will probably increase the efficacy rate that we're seeing for some these patients. And going by what TAR-200 has shown in the BCG unresponsive CIS setting, at least as of now, the sustained durability that we're seeing with this drug at one year is certainly the highest out of all of the approved agents. So, you know, I think whether it be just based off of the mechanism of action of the drug, the delivery system, and also based off of the data, delivery system, certainly seems to have a major role in controlling the disease.
- [Ashish] So, you know, Roger, obviously everything we do is for the patients, right? And it's our role, and I know you do this well, guiding patients to the best possible treatment, but practically speaking, sometimes patients will see something on the news, they'll read something about the latest treatment and unfortunately will be misled. How do you address this in their overall role? I know it's a difficult question, but again, if a patient comes to you and says, hey, I've heard about this latest treatment, it has what looks to me to be the best efficacy, and you don't agree, how do you guide that patient without necessarily disappointing them?
- [Roger] Yeah, no, that's a great question because nowadays, as you know, a lot of the data for these trials that are very much available to patients and they are very well read before they come into clinic to see us and present to us actually what they think is the optimal treatment for them. Ashish, like what you taught me during fellowship, I go by the numbers, you know, I kind of present to them a lot of the data that's been shown in prospective studies studies and in the case of gem/doce, I present to them what's been shown in the real world well performed retrospective analyses. And then again because I think the BCG unresponsive NMIBC disease space was so well defined, you know, by the IBCG and others, that it is somewhat okay for us to kind of look across different trials to look at the, you know, the complete response rates in somewhat of a comparative way. So, you know, I would tend to present all of the numbers to the patients, certainly talk about the toxicity that I've observed personally as well as reported from the trials to the patients and, you know, combining the two together, see if that will sway their decision or not based on what I've presented. And also give them my honest opinion about what I think is the best choice for them.
- [Ashish] Roger, you know, this such an interesting topic. We could chat forever, but I really want to thank you for taking the time in joining us today. You know, I think as treatment options expand and we have, you know, future options available for patients, we'll have to have another visit to think about how the guidelines, including the IBCG guidelines can better reflect this whole complexity and diversity of care that we have currently ongoing, right? And in fact, everything you talked about. So Roger, thank you so much. Always a pleasure.
- [Roger] Always a pleasure chat with you, Ashish, especially on this topic. We've came so far since the day that you and I shared a clinic during my fellowship together, so it's exciting times and look forward to what the future has in store for all of us.
- [Ashish] Absolutely. Take care.
- [Roger] Thank you.
Developed by EPG Health. This content has been developed independently of the sponsor, Pfizer, which has had no editorial input into the content. EPG Health received funding from the sponsor to help provide healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content. This content is intended for healthcare professionals only.
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