Optimizing treatment with intravesical drug-releasing systems in NMIBC

As treatment options expand for patients with non–muscle invasive bladder cancer (NMIBC), intravesical drug-releasing systems (iDRS) have emerged as a novel approach to delivering sustained chemotherapy directly within the bladder. Among these is the gemcitabine intravesical system (Inlexzo), which was approved in September 2025 for adult patients with BCG-unresponsive non–muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors.

The gemcitabine intravesical system represents a novel addition to the treatment landscape, offering continuous drug exposure over a defined treatment cycle while reducing the need for repeated instillations. Data indicate that 77% of the drug from the gemcitabine intravesical system is released within the first week of the 3-week treatment cycle, suggesting important implications for patient tolerability and treatment benefit.¹ However, as with any indwelling intravesical therapy, its use introduces practical considerations around patient selection, tolerability, and adverse event management.

A recent expert panel paper provides practical guidance for urologists on optimizing the use of iDRS systems, with a particular focus on adverse event mitigation and procedural best practices. Drawing from both clinical trial experience and real-world adoption, the recommendations emphasize proactive patient counseling, careful assessment of baseline urinary symptoms, and standardized approaches to managing common toxicities associated with intravesical drug delivery.²

In the following interview, David Morris, MD, FACS, president of Urology Associates of Nashville in Tennessee, discusses how these principles apply in clinical practice. He highlights key strategies for counseling patients receiving the gemcitabine intravesical system, approaches to managing lower urinary tract symptoms and other adverse events, and considerations for maintaining patients on therapy long enough to achieve meaningful clinical benefit.

Urology Times: What are some of the general principles or prophylactic measures that urologists should consider when counseling patients who are receiving these systems?

Morris: For patients who are going to have a drug-releasing system placed in their bladder, it's important that we [provide] some upfront expectations and counseling to the patients. I like to think of at least grading out what the patients’ preexisting lower urinary tract symptoms are. If they have a lot of storage and irritative symptoms, they need to be counseled that they could be prone to having issues with any devices placed in the bladder.

Outside of that, the basics are [how we would counsel patients with] overactive bladder or people with indwelling stents, and that's remaining well-hydrated, trying to avoid caffeine, or [trying to avoid] bladder irritants in their diet. Then sometimes we will tell patients that if they're really bothered, we can add in medications that may assist with quieting the bladder urothelium.

Urology Times: How does upfront assessment, such as screening for LUTS, influence patient selection and your ability to keep patients on therapy long enough to receive meaningful benefit?

Morris: Many of these patients have already been beat up with intravesical therapy, and they may have baseline lower urinary tract symptoms, both in men and in women. Many of them are already on medications for overactive bladder, so it's trying to judge how bothersome their storage symptoms are. They do have to withhold the device in their bladder for a period of several weeks to allow the drug elution out into the urine, and it comes down to patient bother. If they're willing to give it a try, I think it's a reasonable thing to do even in patients with baseline lower urinary tract symptoms. If someone has urge incontinence throughout the day and is unable to hold any urine within their bladder, then at that point, it's probably that they're going to have difficulty with any intravesical therapy.

Urology Times: How does the reported 77% rate of drug from the gemcitabine intravesical system being released within the first week of the 3-week treatment cycle¹ factor into your recommendations for this treatment option?

Morris: The fact that most of the drug is eluted during the first week makes me feel better if someone is unable to tolerate it and we have to remove it. That was extremely rare within the study; over 90% of patients are able to keep the product in without having treatment-related adverse events. Placements were also 99% successful in clinical trials in the development of this drug-releasing system. I'm not particularly worried about patients having to get it removed, but at least that does make you think that even if they're not able to keep it in the full 3 weeks, they're able to get some benefit from having drug within their system.

Urology Times: What has the real-world evidence shown about the rate of adverse events with these systems, and how does that compare to the safety profile seen in clinical trials?

Morris: The real-world data and the clinical trials show that these therapies are well-tolerated. Almost all of the [adverse events] from the clinical trials are grade 1 and grade 2, and most frequently what we'd expect: frequency of urination, dysuria, burning, some urgency of urination, and intermittently, hematuria. There were some patients in the study [who had urinary tract infection] UTI, and certainly in the real world, any manipulation is going to [make patients] prone to UTI. The guidance would be to follow whatever would be your standard protocol for catheterization or manipulation of the bladder; you can use antibiotics around the time of a placement or an exchange of one of these devices.

Urology Times: How does the panel recommend patients with dysuria, UTI, and hematuria are managed?

Morris: A lot of it is still upfront counseling to the patient and what expectations are, so that they are aware that the symptoms they're having do not mean that the drug is causing a problem. It's almost an expected [adverse] effect of the treatment. Focusing back in on the easy things, hydration, avoiding bladder irritants, often adding in overactive bladder [medications], or urine cultures or appropriate antibiotics if somebody has a UTI. Some of the anti-spasmodics or [urinary analgesics], like Phenazopyridine (AZO; Pyridium), can be utilized over the counter. Things like AZO can help with some bladder irritation, especially if they're having pain related to the spasms.

The end resort is taking the device out. In the study, it was also an option if patients were having tolerance issues, to skip a cycle, let their bladder quiet back down, and then reintroduce the drug product. I do think all cards are on the table. Most of it can be managed upfront with some counseling that it's expected and it's not a problem that needs to lead to a stop of the therapy. As long as patients are aware of that upfront, they're often able to tolerate and get through this induction phase. The maintenance phases are fairly short, too.

Urology Times: When symptoms such as dysuria or overactive bladder persist despite initial management, how do you determine when to escalate evaluation vs when is it appropriate to pause or resume iDRS treatment after symptom resolution?

Morris: For symptoms that are more persistent and bladder retraining and hydration have not been effective, you could consider cultures. If they're not showing anything, you can evaluate with cystoscopy. That can be part of removing the device, but it also lets us evaluate if the bladder is particularly inflamed or irritated from the device. It could be something that then could be removed. You can have a holiday without something within the bladder. In certain circumstances, you could try steroid doses in a short cycle to help with inflammation or overactive bladder [medications such as] anticholinergics or beta 3 agonists. Those are all medication cocktails that can be utilized if someone's having persistent symptoms. If you've gone through all those steps, and it's really just not getting better, and it's intolerable from a patient standpoint, take it out, let the patient try to recover, and if they get back to where they're less bothered, then you can talk about reintroduction.

Urology Times: When a patient requires early device removal because of adverse events, how do you assess whether they still have derived meaningful therapeutic benefit?

Morris: Ultimate therapeutic benefit is the disease-free interval, both in terms of having a complete response or clearance of your bladder and how long you can maintain that. There’s no way to tell patients, “This is the amount of benefit you've gotten.” It hopefully pays out, just as it did in the clinical trial, that it's a longer duration until you have a recurrence. It's no different than any of the intravesical therapies we've used historically, like BCG induction, where if you have to stop after 4 or 5 doses, the answer for the patient is we won't know your therapeutic benefit until we see how long it takes for you to have a recurrence. In the studies, there were patients who were not able to get every cycle, but that doesn’t mean that they weren't able to have durable benefit.

Urology Times: Is there anything else that you wanted to add?

Morris: The publication is a grouping of the experiences of heavy implanters, both from the trial and moving into the real-world experience. That trial program goes back years. There are patients who've been through hundreds of placements in some of the clinical trial programs across all of the platforms; any of these intravesical drug-releasing systems all have very similar toxicity exposure. Urologists are very comfortable managing these [adverse] effects. They're similar to patients who have stents in place. We have a whole cadre of different techniques to try to minimize their day-to-day bother from those intravesical therapies.

Patients also tend to be a bit more tolerant of something that's delivering a treatment for cancer. [This is] different than someone who's getting a stent out next week, and they say, "I just want it out now." They're willing to tolerate a bit more if you can say that this is a cancer therapy and we have this prescribed regimen that we're trying to get through this number of weeks of treatment. Patients are then sometimes willing to say, "All right. It's a chemo-eluting device. I'm willing to try to tolerate it and tough it out, because I know that it's going to be the best for my cancer response."

REFERENCES

1. Inlexzo. Johnson & Johnson. Accessed April 2, 2026. https://www.inlexzohcp.com/

2. Pradere B, Schuit M, Guerrero-Ramos F, et al. Side effect management and procedural best practices with indwelling intravesical drug-releasing systems in the treatment of bladder cancer: recommendations from expert panels. Curr Opin Urol. 2026;36(1):123-133. doi:10.1097/MOU.0000000000001350