Changing Chemotherapy Delivery in BCG-Unresponsive Bladder Cancer

Ongoing shortages of Bacillus Calmette-Guérin (BCG) and a push toward bladder-preserving options have driven interest in new intravesical drug delivery systems for non–muscle invasive bladder cancer (NMIBC).

CancerNetwork® spoke with Goutham Vemana, MD, chair of the Department of Urology at Allegheny Health Network (AHN) in Pittsburgh, Pennsylvania, about AHN’s launch of the gemcitabine intravesical system (Inlexzo; formerly TAR-200), making AHN the first health system in western Pennsylvania to offer the therapy. The FDA approved the system in September 2025 for adult patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors, based on cohort 2 of the phase 2b SunRISe-1 trial (NCT04640623), which showed a complete response rate of 82%.¹ The device is placed during an outpatient procedure and continuously releases chemotherapy over a 21-day cycle, with most patients completing 8 cycles over 6 months.²

Vemana discussed how the system’s continuous-release mechanism changes bladder drug exposure compared with standard gemcitabine instillations, what the in-office workflow looks like for urology and advanced practice teams, barriers to access and how AHN’s navigation programs address them, as well as opportunities for closer collaboration between urology and medical oncology. In addition, he highlighted strategies for managing local urinary adverse effects (AEs) over a multi-week indwelling course, how BCG supply constraints are reshaping real-world decision-making, and where research stands on biomarkers to guide treatment selection.

CancerNetwork: How does the mechanism of the delivery system alter drug kinetics, and what clinical advantages does this sustained drug exposure offer over standard gemcitabine instillations?

Vemana: Starting from what standard gemcitabine instillations look like historically: these are intravesical treatments where a catheter is placed, and we instill about 2g of gemcitabine into the bladder. It typically dwells in the bladder for 1 to 2 hours, based on patient tolerability, longer is better, and the goal is to coat the surface of the bladder in this chemotherapy to treat and prevent bladder cancer recurrences.

You tend to get a peak-and-trough pattern: a high dose of the drug administered into the bladder, but it is only exposed for a short period of time. The advantage of the gemcitabine intravesical system, TAR-200, is that it is constantly emitting gemcitabine at a steady state for a couple of weeks, so the bladder is exposed to the treatment over a much longer period. Studies have shown that this yields better depth of penetration of the drug into the layers of the bladder. One important finding from these studies is that despite this depth of treatment, the drug does not absorb systemically; it is not being absorbed into the bloodstream. You get this maximal advantage of therapy over a long period of time without systemic exposure, and that is why the efficacy is better.

What does the clinical workflow look like for the system, and how are urology, medical oncology, and advanced practice providers [APPs] coordinating placement, 3-week retention monitoring, and removal cycles within the outpatient setting?

This is more reliant on the urologist than some of the other treatments. The typical intravesical therapies are often done by our nursing staff or medical assistants [MAs], placing catheters and instilling the medication. In a large system like ours, patients come into our cancer centers for those types of treatments. The TAR-200 treatments are coming back to the urologists, because while some of our APPs can help place the devices, an APP or urologist has to remove the device and insert the new one, and usually you need someone who can perform a cystoscopy to do that.

The workflow is a little more involved. It is not terribly complex for most urology practices, but it is more involved for the patient. You are not just instilling the medicine and walking away; you have to take the old device out, put a new device in, and you are doing that about every 3 weeks. As far as how we are integrating this with other providers, many urology practices are extremely busy, and doing this every 3 weeks for the initial treatment phase, which is 8 treatments in a row, can be cumbersome for physicians to handle alone.

It is important that we train our APPs to do some of these treatments and alternate. We are still figuring out how we will incorporate that, but as the volume of these treatments increase, or as future treatments expand, we will need to involve our physician assistants [PAs] or nurse practitioners in some of these remove-and-replace procedures.

For patients with high-risk BCG-unresponsive NMIBC who are candidates for bladder-sparing therapies, what barriers to accessing treatment exist, and how is AHN leveraging patient assistance and navigation programs to ensure equitable access and overcome reimbursement challenges?

Some of the barriers are logistical for patients. We see a lot of patients across western Pennsylvania, and fortunately, for a large system like ours, we have multiple office sites throughout the region that can offer these treatments, which helps. There are some nuances with insurance and coverage and where treatments can be administered. in a network like ours, there are certain places where we are allowed to administer these treatments, which does restrict us somewhat. Some private practice urology groups are doing this in their offices without too much difficulty. Insurance coverage is always a concern, but many groups have not experienced too many problems. When I have talked to urology colleagues at national meetings who have started these treatments, they have not found too many barriers to reimbursement. For patients with limited finances, there are many foundations that companies like Johnson & Johnson work with, along with patients, to help minimize the financial toxicity of these treatments.

How can urologists and medical oncologists collaborate more effectively to increase awareness of this drug delivery system, and where does it fit relative to systemic immunotherapies or clinical trial options?

Collaboration is extremely important. Patients, whether in our system or others, are being referred, and they are not always seeing the urologist first. It is not uncommon for a patient, even with [muscle-invasive bladder cancer (MIBC)], to see a medical oncologist before they see us. Fortunately, in a group like ours, our medical oncologists are tightly integrated with us, and we have multidisciplinary conferences where we discuss these technologies.

They are aware of these types of treatments and have helped us bring some of them into the network by working with our oncologic pharmacy. We have pretty good access in a system that may not be as tightly integrated as AHN. It is important to interface with primary care doctors, but mainly with medical oncology providers, since if they are not seeing patients directly, those patients will be referred to an oncologist or urologist for these issues. Keeping a good, productive relationship and letting colleagues know we have these new treatments on board is key.

Given that the system remains in situ for weeks at a time, what local urinary adverse effects [AEs] are you most concerned about, and how can multidisciplinary care teams proactively manage these to preserve patient quality of life and optimize treatment completion rates across all cycles?

Even with the historic intravesical therapies, like BCG and gemcitabine/docetaxel, patients experience treatment toxicity, mostly lower urinary tract symptoms: bladder pain, frequency, urgency, sometimes hematuria, and infection. These are the most common [AEs]. For a device that dwells in the bladder for weeks at a time, emitting a steady state of chemotherapy, some patients can experience a bit more of these [AEs], though everybody is different; we tend to see a bit more frequency and urgency. It is also important to know that many of the patients receiving these treatments have had a lot of prior treatment, so they may not be representative of the patients enrolled in the studies. Some of these patients’ bladders have already been sensitized to intravesical therapy from earlier lines of treatment.

This idea of bladder sensitization is real. To bring together a multidisciplinary team to minimize these symptoms, it is important that office staff, support staff, [medical assistants], nurses, and [physician assistants] understand the possibility of these symptoms, and understand the patient population they are treating. It is important to spend more time counseling patients on what they may or may not experience.

Hydration is extremely important with these indwelling devices, so we counsel patients to stay well hydrated. We can also pretreat patients, starting anticholinergic therapy about a week before treatment begins, using beta-3 agonists, sometimes phenazopyridine [Pyridium], or other agents like Uribel, and sometimes patients need extra pain medication to get through treatment. You might need to do more upfront management for the first couple of cycles, and patients tend to tolerate it better after that. A lot of it comes down to educating patients and spending extra time with them, because we really want people to start these treatments and finish the multiple rounds of therapy to get the most efficacy from them.

The global supply constraints surrounding BCG have forced urologists to ration doses, prioritize high-risk subpopulations, or use off label intravesical chemotherapy regimens, such as a combination of gemcitabine and docetaxel. How drastically has this supply volatility altered real-world clinical decision-making, and do novel drug delivery platforms offer a path toward permanently decoupling disease management from BCG availability?

BCG availability, or the lack of it, has been a huge problem for urologists in the US, and limited access can compromise patient care. BCG is a widely used, well-accepted treatment for this disease, and there is [an] expectation from patients that they will receive it; patients are shopping [across hospital systems] to try to get BCG. We are now in a situation where patients have access to more information, and perhaps more alternative options. I get a lot of referrals from outside of Pittsburgh…for alternative therapies because patients cannot get BCG, and some outside providers are not quite as aware of these newer options. It leads to a lot of anxiety for patients when they feel they cannot get the treatment the studies say they should be getting.

Even though we are often using gemcitabine and docetaxel, which is an excellent therapy as well, some of these patients are getting it because they could not get BCG, and if they [progress on] that, it is getting them to modern treatments like TAR-200 potentially a bit earlier, or in a different sequence. Before these treatments were available, there was more anxiety, because patients would often say, “If I cannot get BCG and gemcitabine and docetaxel [failed me], what can I do? There is only pembrolizumab [Keytruda]," and not all medical oncologists were comfortable delivering that. Sometimes the efficacy data were not as strong as we would like.

What clinical biomarkers, patient-specific characteristics, or disease features do you rely on when choosing between systemic therapy, novel intravesical agents, or radical cystectomy?

That is frequently raised at national conferences: who is right for what treatment? What we are talking about is tailored therapy, and it is still not well understood who will respond to a treatment like TAR-200 vs gemcitabine and docetaxel, BCG…or the other options available. There are some emerging biomarkers, like urinary tumor DNA, circulating tumor DNA, and other molecular markers we are looking at, but while these markers can indicate disease burden, whether local or systemic, they do not consistently tell us which patient will respond to which therapy. While we have a surge of new treatments, many of these studies are single-arm studies, so there is no head-to-head comparison to guide patient selection.

There is a trial that has finished accrual called the phase 3 BRIDGE trial [EA8212 (NCT05538663)], which is comparing BCG to gemcitabine and docetaxel, but those results will not be published for a couple more years. Even for that comparison, we do not yet know if gemcitabine and docetaxel is truly equivalent to BCG…Right now, none of these markers are giving us reliable information to tailor treatment for individual patients.

References

1. U.S. FDA approval of INLEXZO™ (gemcitabine intravesical system) set to transform how certain bladder cancers are treated. News release. Johnson & Johnson. September 9, 2025. Accessed September 9, 2025. https://tinyurl.com/4zjz22z7
2. AHN urology expands bladder cancer treatment options with innovative INLEXZO therapy. News release. Allegheny Health Network. June 16, 2026. Accessed August 4, 2026. https://tinyurl.com/5tbnpa8t