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BackTable / Urology / Article
Intravesical Therapy for Bladder Cancer: Current Standards & Emerging Options
Sam Strauss • Updated May 14, 2025 • 36 hits
Intravesical therapy remains a mainstay of treatment for patients with low and intermediate-risk non-muscle invasive bladder cancer (NMIBC), particularly in cases where there is high risk of recurrence. While transurethral resection of bladder tumor (TURBT) is essential for initial control and staging of NMIBC, many patients require additional therapy to reduce the likelihood of disease recurrence. Bacillus Calmette-Guérin (BCG) and gemcitabine are among the most commonly used intravesical agents, each with distinct efficacy profiles and side effect considerations.
Treatment planning typically involves weighing tumor grade, recurrence history, and logistical factors ranging from drug availability to cost, and administration setting.
Newer therapies are expanding the intravesical toolkit and shifting the landscape toward more individualized, bladder-sparing strategies. UGN-102, a chemo-hydrogel designed for low-grade intermediate-risk disease, offers a non-surgical alternative to repeat TURBT. TAR-210, another new drug delivery platform, delivers sustained-release erdafitinib for patients with FGFR mutations, while gene therapy Adstiladrin introduces a novel approach for patients with high-risk, BCG-unresponsive disease. These innovative therapies are offering new solutions to patients who previously had few non-surgical treatment options, and reshaping how physicians manage NMIBC and recurrent bladder cancers.
This article features excerpts from the BackTable Urology Podcast. You can listen to the full podcast below.
The BackTable Urology Brief
• Intravesical therapy is commonly used following TURBT to reduce recurrence in low and intermediate-risk NMIBC.
• Bacillus Calmette-Guérin (BCG) and gemcitabine remain the primary agents used in most intravesical treatment regimens.
• Patient selection for intravesical therapy depends on tumor grade, multifocality, recurrence history, and side effect tolerability.
• UGN-102 is a chemo-hydrogel formulation of common chemotherapeutic agent mitomycin C designed for low-grade intermediate-risk disease as a non-surgical option.
• Adstiladrin is an FDA-approved gene therapy for high-risk, BCG-unresponsive NMIBC, delivered via adenoviral vector.
• TAR-210 is a sustained-release intravesical agent delivering erdafitinib for FGFR-altered bladder cancer.
Table of Contents
(1) Standard Intravesical Approach for Non-Muscle Invasive Bladder Cancer
(2) Targeted and Non-Surgical Options in Non-Muscle Invasive Bladder Cancer
(3) New Options for High-Risk, Refractory Non-Muscle Invasive Bladder Cancer
Standard Intravesical Approach for Non-Muscle Invasive Bladder Cancer
Reducing recurrence of NMIBC following TURBT in patients with low or intermediate-risk disease often relies on intravesical therapies. Gemcitabine, a chemotherapy alternative, is often used as an agent for these therapies with low-risk patients, or those with an intolerance to BCG. Bacillus Calmette-Guérin (BCG) remains the most commonly used first-line agent, particularly for intermediate-risk or early high-risk disease. The decision to initiate therapy – and which agent to use – depends on tumor characteristics, recurrence patterns, and patient-specific considerations such as immunocompetence and comorbidities.
Repeat TURBT is frequently recommended in cases where high-grade pathology is present or when muscle is absent in the initial specimen. Even in low-grade tumors, re-resection may be indicated if there is concern about staging accuracy or incomplete removal. Postoperative installation of gemcitabine is commonly performed after TURBT for low-risk disease, with evidence supporting its ability to reduce short-term recurrence if given within 6 hours.
BCG remains an effective option, but not all patients tolerate it well, and national shortages have limited its availability in some settings. In such cases, gemcitabine is often substituted, either alone or in combination with docetaxel. These regimens are chosen based on institutional experience, patient tolerance, and risk stratification. While these therapies are well-established, patient selection and logistical execution remain essential to optimizing outcomes.
[Dr. Aditya Bagrodia]
I generally will give them all options, but at the end of the day, if you were my dad or my brother, whoever would probably just monitor and look in three months if they ask, "What would you do, doc?" Maybe it's the TA, the low-grade, small focus of high-grade, T1 low-grade that always is a bit of a weird entity, first off, a little bit challenging to believe just given the incidents. Anything of T1 low-grade? What do you guys think about that?
[Dr. Amir Salmasi]
For me, I highly recommend that the patient receives adjuvant treatment. Maybe not for three years as a swab trial, maybe at least one year, and then highly recommend to elect from the Gem/Doce versus BCG. Again, we have a trial and you're our local PI, the bridge trial, push for it. I highly recommend even there's a small high-grade capillary to consider the adjuvant treatment.
[Dr. Betsy Koehne]
I would also use intravesical adjuvant treatment for that situation. I think also would depend on whether we were in a more acute BCG shortage time or whether there was BCG, about whether I would go with chemotherapy or BCG in that situation, but then also the patient's tolerance with Gem/Doce of having multiple installations and just spending longer in clinic. That's also something that I bring up with them when considering that.
[Dr. Aditya Bagrodia]
Is it fair to infer that if BCG were abundantly available, BCG would be the preferred intravesical option for a TA high-grade tumor? It would for me.
[Dr. Betsy Koehne]
Yes.
[Dr. Aditya Bagrodia]
The trial would be the preferred option, preferred, preferred. In the guidelines, it says intravesical immunotherapy or intravesical chemotherapy. If you're using chemotherapy, is this single agent gemcitabine? Is it Gem/Doce? Is it something else?
[Dr. Amir Salmasi]
For me it is Gem/Doce. I don't believe in the single-agent chemo as adjuvant treatment. Only single-agent just for a perioperative time, but for induction and maintenance, I highly also recommend the maintenance of the combination of the Gem/Doce.
[Dr. Betsy Koehne]
I would also try to use at least combination Gem/Doce if we're doing chemotherapy for a high-grade tumor.
[Dr. Aditya Bagrodia]
Maybe taking a step back, if it was a multifocal low-grade or a larger low-grade that puts you in intermediate risk, is that intravesical chemotherapy single agent or is it combination?
[Dr. Betsy Koehne]
I would typically start with a single agent if they wanted to do intravesical chemo. You can always go up from there, but I think that's in the space where-- you're not usually going to lose any ground in terms of progression risk, so I think it's reasonable to start with less.
[Dr. Amir Salmasi]
You mean single agent as a preoperative treatment or just like you do as induction?
[Dr. Aditya Bagrodia]
No, like weekly gemcitabine, it's like a multifocal low-grade. Betsy, I would agree with you. If they had like multifocal low-grade and they wanted to be aggressive and proactive, I would say, okay, we can do six weeks of induction gemcitabine and then monthly gemcitabine. Even that can be a bit of a debate depending on how everything went with the first go around for a low-grade.
If they progress, maybe we won't focus so much on that because I think that can progress to higher-grade tumors. That leads us into the whole conversation of BCG refractory disease. How about three months cysto and they didn't receive anything and now they've got multifocal low-grade tumors? Perhaps just for the sake of time, we completely resect those, whether that's a biopsy resection in the clinic or a trip to the OR. Now what? Now they're squarely in intermediate risk however they sort it out, right? Betsy, maybe we'll start off with you.
[Dr. Betsy Koehne]
If they hadn't had intravesical gemcitabine yet, I would just start with that. I rarely use Mitomycin C. I think I just grew up in the urology world where people were scarred by that, so I don't usually use it, although I have more recently seen people using it and saying that it's going okay. Then otherwise after that would see if we had a clinical trial open for another agent. Typically, I would just start with intravesical monotherapy gemcitabine if they hadn't had that yet.
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Targeted and Non-Surgical Options in Non-Muscle Invasive Bladder Cancer
Recent advances in drug delivery systems have introduced intravesical therapies designed to improve accessibility, reduce the need for multiple surgeries, and offer longer dwell times for improved tumor contact. UGN-102, a reverse thermal gel formulation of mitomycin C, is one such option developed for patients with low-grade, intermediate-risk NMIBC. The gel is instilled in liquid form and solidifies at body temperature, allowing for prolonged exposure in the targeted area. Early studies show promising efficacy in avoiding repeat TURBT, particularly for patients with multifocal or recurrent tumors who are not ideal surgical candidates.
TAR-210 – another innovative delivery system – uses a sustained-release intravesical platform to deliver FGFR targeted drug erdafitinib directly to the urothelium. It is intended for patients with FGFR-altered NMIBC, and while the therapy is still investigational, the approach offers the potential for targeted treatment without systemic toxicity. These delivery mechanisms expand the role of intravesical therapy beyond traditional chemotherapy, offering non-surgical solutions with improved tolerability and patient adherence.
As more patients seek bladder-sparing options or present with recurrence in the context of comorbidities or high surgical risk, the value of these therapies continues to grow. Their success, however, still depends on appropriate patient selection, appropriate genetic profiling, and a clear understanding of long-term outcomes—many of which are still under active investigation.
[Dr. Amir Salmasi]
…I think the most important thing is risk stratification. As you said, the BCG is not going to work for people with a low-risk bladder cancer. We should stop overutilization of the BCG for a low risk. I think that's the first step, to get appropriate risk stratification. Based on that, then guidelines comes into play that BCG is not the treatment of choice for every bladder cancer.
[Dr. Aditya Bagrodia]
Okay. Let's talk a little bit about the trial. You mentioned targeted therapies, FGFR3 inhibitors, you mentioned chemoablation. Maybe we can at least spend a moment about that. Any familiarity with UGN-102? Does either of you all want to give us a little quick walkthrough what that is, how it's instilled?
[Dr. Amir Salmasi]
I can talk about the UGN. The delivery system is like a thermogel called RTGel. This gel when is in the cold temperature is a liquid, but it goes to body temperature, it just performs a gel and it stays longer time. Instead of just drain right away, it takes about six or eight hours the body get rid of this gel. When we put the mitomycin in this gel, we administer through the catheter into the bladder, it stays longer time, and over the six, eight hours, patient urinates and eliminates the drugs. The concept comes towards like a chemoablation.
We said if the people has like a small multifocal or immediate risk bladder cancer, are we worth that we give this treatment or we should go and surgical remove it? There was a two trial, they used like a Phase 3 trial. One of them was ATLAS trial. That was a randomized trial that compared to people receiving UGN-102, and if they had a recurrence, they go to take a transurethral resection. One was like a UGN plus/minus TUR and the control arm was just a TUR with no adjuvant treatment.
At three months, complete response rate in these two groups was similar, but the long term in 15 months, the people that receive UGN upfront had like a 72% response rate versus 50% of the people with the TURBT. There was some problem with this trial because they stopped early, the sponsor, because they want to try with different agent. It's not powered based on this patient that they recruited, but overall showed that a signal towards a better outcome of the people receive this UGN upfront, then they go TUR.
The other thing was like the people with the TURBT arm did not receive any adjuvant treatment. They did another trial, they envision was like a Phase 3, but single-arm, that all the people just received the UGN-102, and in three months, if they have a complete response, they follow it. Anytime they have a recurrence, start of a care, TURBT adjuvant treatment. Based on that also, they showed that very high complete response rate in three months after the UGN-102.
I think that it's going to be approved early in 2025 for the people with the intermediate risk bladder cancer that has like a multifocal small and then we think that maybe we don't want to bring for some reason to the operating room, or we discuss the patient or patient prefers that. One of this trial use UGN-102.
[Dr. Aditya Bagrodia]
…I think it's exciting. It's really nice that there are companies paying attention to this relatively niche disease state. Betsy, maybe I could just ask you to give us a little flavor for some of the trials that have you excited about next options for our patients.
[Dr. Betsy Koehne]
Amir mentioned earlier the erdafitinib pretzel, the TAR-210, which you also mentioned earlier, so about 60% to 80% of low-grade non-muscle invasive bladder tumors will have an FGFR2 or 3 alteration which we think is an oncogenic driver. Those are susceptible to erdafitinib. They initially looked at this in the THOR-2 study. There was an exploratory cohort in which patients had an oral dose of erdafitinib. That was a trial in which they left a marker tumor, so they did a TURBT, but left one of 5 to 10-millimeter tumor and then looked at follow-up. They had pretty good rates of response, but there was toxicity as it was a systemic treatment.
So far, I think at ESMO in 2023, they just had results from about 15 patients, but they had 87% with a complete response. It's a very early response rate, but I think that mechanistically it's exciting just that it's a great example of us learning more about the biology of the disease and applying a more targeted treatment. Hopefully, this would be very different mechanism. Maybe something will give us more lasting results.
New Options for High-Risk, Refractory Non-Muscle Invasive Bladder Cancer
Treatment options have historically been somewhat limited for patients with high-risk, BCG-unresponsive NMIBC. Radical cystectomy remains the gold standard, but not all patients are candidates for surgery due to age or comorbidities. There are also a significant number of patients who decline for personal reasons, or quality of life concerns. For this patient population in particular, the recent FDA approval of Adstiladrin presents a notable expansion of treatment options. Adstiladrin (nadofaragene firadenovec) is a gene therapy delivered via intravesical instillation, that may offer a non-surgical alternative to radical cystectomy. The therapy uses a non-replicating adenovirus vector to deliver the human interferon alfa-2b gene into bladder epithelium, promoting a local immune response designed to control tumor growth.
Adstiladrin is administered once every three months via catheter, with most patients receiving four doses over the course of a year. In clinical trials, the treatment demonstrated sustained positive response rates in patients with bladder carcinoma in situ, with or without papillary disease, and offered a well-tolerated alternative to cystectomy. While longer-term data is still being collected, early results suggest meaningful disease control for appropriately selected patients.
Gene therapy approaches like Adstiladrin provide exciting new options for patients who may not be eligible for other treatments. These advances offer hope for maintaining quality of life while minimizing disease progression risk, particularly for those seeking bladder preservation in the setting of an aggressive prognosis.
[Dr. Amir Salmasi]
…Adstiladrin now also has an adjuvant setting for the intermediate-risk bladder cancer. If he patient has an intermediate risk, they receive quarterly of Adstiladrin that is an adenovirus that induces interferon, one of the elements of the immune response in the bladder. They had good results and the BCG unresponsive. Now they're bringing to the earlier stage and the intermediate risk. That one also patients like there's a randomized trial and if people on the control arm develop recurrence to cross over, they can receive the Adstiladrin. It's another interesting new trial, will be exciting trial.
[Dr. Aditya Bagrodia]
It kind of makes sense, right? It's like you start out with the BCG unresponsive and then it's BCG naïve for high risk, and now it's more like intermediate risk. It's a crazy thought. It's exciting that you have these tools in your toolkit for people with maybe non-life threatening but recurrent and highly inconvenient bladder cancer. It's also like a trip that they could be receiving medications that are literally like gazillions of dollars. I guess as things mature and perhaps get out of their period of being proprietary, et cetera, it's really cool to see these things and meet patients where they're at.
It's worth asking, I'm curious, have you guys ever done a cystectomy for recurrent low-grade bladder cancer?
[Dr. Betsy Koehne]
No, never.
[Dr. Aditya Bagrodia]
It's like you don't want to do that at all costs. I said BCG for low-grade seems wrong and a cystectomy for low-grade seems awful, but I don't discount how psychologically and physically challenging. Sometimes people get a TURBT and they're off for like a month and it's like a whole thing. It's nice to see these options. Here it is, we've been an hour talking about low-risk and intermediate-risk bladder cancer and want to be respectful of y'all's time. Perhaps, as we wrap up, any parting thoughts for the listenership?
[Dr. Betsy Koehne]
I would just echo what you're saying. I think even though for us as clinicians, and even though it doesn't really distress me very much about finding a low-grade or recurrent low-grade tumors, but I'm always reminded with my patients that it is something that is distressing for them. Just the recurrence and the anxiety around recurrence and the procedures, which even though we do them all the time, can still come with complications. It'd be great if there were no more super recurrent low-grade tumors. I hope that that's where we're going in the future.
Podcast Contributors
Dr. Elizabeth Koehne
Dr. Betsy Koehne is a urologist at the University of WIsconsin-Madison School of Medicine in Madison, Wisconisin.
Dr. Amir Salmasi
Dr. Amir Salmasi is a urologist at UC Sand Diego Health in San Diego, California.
Dr. Aditya Bagrodia
Dr. Aditya Bagrodia is an associate professor of urology and genitourinary oncology team leader at UC San Diego Health in California and adjunct professor of urology at UT Southwestern.
Cite This Podcast
BackTable, LLC (Producer). (2024, December 6). Ep. 204 – Managing Low & Intermediate Risk Bladder Cancer [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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