The Role of the Pharmacist in Treating Non–Muscle Invasive Bladder Cancer

Bladder cancer is the sixth most common cancer in the US, affecting more than 84,000 people annually.^1,2 Approximately 75% of new diagnoses, or about 64,000 annual cases, are non–muscle invasive bladder cancer (NMIBC). NMIBC is significantly more common in White men compared with other races. The majority of cases occur in individuals aged 55 years or older.³

NMIBC represents a spectrum of disease confined to the bladder’s inner layers (urothelium or lamina propria) and not invading the detrusor muscle.⁴ High-risk NMIBC typically includes high-grade tumors, carcinoma in situ (CIS), multiple or larger tumors, or recurrence.⁴

Current Treatment Modalities

The standard initial treatment involves transurethral resection of bladder tumor (TURBT), followed by intravesical therapy with BCG.^4,6-8 TURBT is an invasive procedure and is usually performed under general anesthesia. Oftentimes, patients require repeated procedures, increasing cumulative morbidity and resource use.^4,6-8 BCG is a live attenuated form of Mycobacterium bovis and is the most widely used intravesical agent.^6,8

However, a subset of patients relapse or progress, resulting in BCG-unresponsive disease.^4,6 For these patients, radical cystectomy is often recommended, but many patients are ineligible due to comorbidity or age, or they decline surgery due to quality-of-life considerations.^4,6 There are significant unmet medical needs for effective, bladder-sparing therapies in BCG-unresponsive NMIBC, especially CIS with or without papillary disease.⁴ Current bladder-sparing treatment options include systemic immunotherapy with pembrolizumab (Keytruda; Merck), gene therapy with nadofaragene firadenovec (Adstiladrin; Ferring Pharmaceuticals), or immunomodulatory therapy using nogapendekin alfa inbakicept-pmln (Anktiva; ImmunityBio) plus BCG.^4,7,8

Despite recent advancements, the unmet need in NMIBC remains due to a high number of nonresponders, limited effectiveness, and low durable response rates in many patients.^9-13 Current bladder-sparing options fail for many patients with NMIBC because the immune microenvironment is often nonreactive or suppressive, tumor biology varies widely between patients, intravesical delivery limits drug contact and penetration, adaptive resistance develops even after initial success, and anatomical challenges further hinder complete response.^9-13 These are some reasons why research is shifting toward combination regimens, better intravesical delivery systems, and biomarker-guided therapy selection to improve bladder preservation outcomes.^9-13

In patients with low-grade, intermediate-risk disease or instances where BCG is not suitable, intravesical chemotherapy, such as mitomycin C, epirubicin, or gemcitabine, may be used.^14,15 Following TURBT, a single dose of intravesical aqueous gemcitabine has been used off-label for years in NMIBC but shows limited sustained efficacy due to its rapid clearance from the bladder.⁴ Evidence supporting the use of off-label gemcitabine in these patients is based on small mixed cohorts, oftentimes retrospective, and demonstrates complete response rates ranging from 28% to 47% with durability seldom greater than a year.⁴

Different manufacturers have also studied techniques to extend the exposure of treatment with mitomycin and increase its effectiveness, including the use of electromotive gradient to increase transport into the bladder, and the use of hyperthermic and mitomycin/gel combinations.^6,15 Traditional intravesical chemotherapy involves instilling a drug solution into the bladder, holding it for a short period before it is expelled, which limits drug contact time. This led manufacturers to develop new formulations and delivery systems that prolong local exposure and enhance efficacy while minimizing systemic absorption.^8,14 Two examples are mitomycin intravesical gel (Zusduri; UroGen Pharma) and gemcitabine intravesical system (Inlexzo; Janssen Biotech).^8,15

A nonsurgical alternative enabling sustained exposure of mitomycin to the urothelium is Zusduri, a reverse thermal gel (RTGel) formulation for intravesical instillation.^8,15 RTGel for intravesical instillation is a liquid at room temperature that transforms into a gel at body temperature, allowing it to stay in the bladder longer and provide sustained local drug release.^8,15 Through its gelation properties, Zusduri delivers uninterrupted chemotherapy directly into the bladder, allowing the potential opportunity to decrease recurrence, delay time to possible retreatment, and reduce dependence on repeated TURBT.^8,15 The recommended dose of Zusduri is 75 mg (56 mL) once weekly for 6 weeks, instilled via urinary catheter.¹⁵

On September 9, 2025, the FDA granted approval for Inlexzo for adult patients with BCG-unresponsive NMIBC with CIS, with or without papillary tumors.^16-18 This includes patients who are ineligible for, or decline, radical cystectomy.^16-18 Previously known as TAR-200, Inlexzo is designed to deliver sustained, local release of gemcitabine directly into the bladder over time rather than via standard intravesical instillation.^4,8,18 The system is placed via a catheter in an outpatient setting, and no general anesthesia is required.^17,18 Treatments are repeated for up to 14 cycles, or until disease recurrence, unacceptable toxicity, or other stopping criteria.^16-18 The first 8 doses are given every 3 weeks continuously, then one cycle every 12 weeks for the next 6 doses.^16-18 The rationale is that prolonged exposure of the bladder lining (urothelium) to gemcitabine may improve drug penetration and increase tumor cell kill, especially in cases where BCG has failed.^4,16.17 By localizing exposure, systemic toxicity is reduced.^4,16,17

Inlexzo is the first FDA-approved drug-releasing intravesical system for this indication.¹⁷ In a meaningful advancement, Inlexzo is differentiated in its continuous delivery of gemcitabine over 3 weeks via a drug-eluting silicone insert that allows for sustained urothelial exposure and curtails systemic uptake.^4,18 Study results illustrated outcomes not previously seen with conventional off-label use of intravesical gemcitabine, including a significantly greater complete response rate.^4,16-18 The approval represents more than just a new treatment option: It signals a broader shift toward innovative, localized drug delivery systems that may reshape management of certain cancers.^4,16,17 By combining the proven efficacy of gemcitabine with a sustained release intravesical platform, Inlexzo addresses a long-standing gap in care for patients. ^4,16,17

The Role of the Pharmacist in Facilitating Treatment with Intravesical Therapies and Implications for Practice

Pharmacists play a pivotal role in supporting evidence-based practice and the safe and effective use of intravesical therapies for patients with NMIBC. The pharmacist performs a critical role in the multidisciplinary care of patients, where both procedural and pharmacological components intersect, and their expertise bridges clinical and operational aspects of care.

Pharmacists will be involved in formulary decisions, preparation and handling logistics, verifying dosing protocols, and confirming treatment cycles are appropriately scheduled. Their knowledge ensures the appropriate drug reconstitution and stability while maintaining sterile compounding conditions to reduce the risk of contamination and exposure. The pharmacist’s involvement is particularly crucial in navigating complex storage, disposal, and safety procedures, especially for live or hazardous agents, which require strict adherence to protocols that may be unfamiliar to other health care professionals.

Beyond technical preparation, pharmacists provide essential pharmacological insights that optimize therapy outcomes. They assess patient-specific factors—such as renal function, prior treatment response, and risk of systemic absorption—to recommend dose adjustments or alternative regimens. Monitoring for adverse effects—such as urinary symptoms, infections, or rare grade 3 or higher events—is another key responsibility. Pharmacists should collaborate closely with providers to manage adverse effects and provide supportive care when needed. Educating patients on what to expect from intravesical systems, the insertion process, and the importance of follow-up assessments is essential to support adherence and reduce anxiety.

Staying current with emerging and unique drug delivery systems for NMIBC is important for pharmacists to ensure optimal therapeutic outcomes and support evidence-based clinical decisions. As experts in medication management, they must understand Inlexzo’s novel delivery system—a sustained intravesical gemcitabine formulation—and its indication for patients with CIS, with or without papillary disease, who are ineligible for or decline cystectomy. Though the device is inserted by urologists, pharmacy teams are responsible for confirming product availability, understanding dosing intervals, and coordinating care with the clinical team. Pharmacists must also possess a thorough understanding of both the delivery mechanism and therapeutic properties of RTGel therapies such as Zusduri to ensure proper preparation, administration, and counseling.

Pharmacists also help address access and reimbursement challenges, assisting with prior authorizations and connecting patients to support programs. By contributing to shared decision-making and facilitating bladder-preserving care, pharmacists ensure that patients derive the maximum benefit from innovative therapies.

The approval of new treatment options is likely to change the treatment paradigm for patients with NMIBC unresponsive to BCG, especially those who cannot or will not undergo radical cystectomy. For pharmacists, staying current on evolving guidelines, assuring safe use, managing adverse effects, educating patients, and supporting multidisciplinary teams will be essential for integrating new therapies into practice. As the field of uro-oncology continues to evolve, new treatments demonstrate the potential for preserving both the bladder and the patient’s quality of life through precision, patient-centered approaches.

Conclusion

The evolving treatment landscape seeks to prioritize preserving the bladder, lessen procedural burden, and offer more convenient options for patients. Continued collaboration among urologists, oncologists, pharmacists, and patients will be critical to realizing the full benefits of emerging therapies.

In the treatment of NMIBC, the pharmacist’s role in intravesical therapy is indispensable, blending procedural precision with pharmacological expertise. By ensuring the correct preparation, safe handling, and clinical appropriateness of intravesical agents, pharmacists support the broader oncology team in delivering effective, individualized care. Their contribution not only enhances treatment safety and efficacy but also strengthens the implementation of best practices across clinical settings, reinforcing the pharmacist’s evolving role as a key collaborator in cancer care.

REFERENCES

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13. Filon M, Schmidt B. New treatment options for non-muscle-invasive bladder cancer. Am Soc Clin Oncol Educ Book. 2025;45(2):e471942. doi:10.1200/EDBK-25-471942

14. Joice GA, Bivalacqua TJ, Kates M. Optimizing pharmacokinetics of intravesical chemotherapy for bladder cancer. Nat Rev Urol. 2019;16(10):599-612. doi:10.1038/s41585-019-0220-4

15. Zusduri. Prescribing information. Urogen; 2025. Accessed October 8, 2025. www.urogen.com/download/pdf/zusduri_prescribing.pdf?_gl=1*132ss2f*_gcl_aw*R0NMLjE3NTk4NjUzMjQuRUFJYUlRb2JDaE1JOW9XYW11bVNrQU1WQTlQQ0JCM0NtUm1NRUFBWUFTQUFFZ0tkeXZEX0J3RQ..*_gcl_au*MjEyNjY4MzI5MC4xNzU5ODY1MzI0

16. FDA approves gemcitabine intravesical system for non-muscle invasive bladder cancer. FDA. September 9, 2025. Accessed October 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gemcitabine-intravesical-system-non-muscle-invasive-bladder-cancer

17. US FDA approval of Inlexzo (gemcitabine intravesical system) set to transform how certain bladder cancers are treated. News release. Johnson & Johnson. September 9, 2025. Accessed October 8, 2025. https://www.jnj.com/media-center/press-releases/u-s-fda-approval-of-inlexzo-gemcitabine-intravesical-system-set-to-transform-how-certain-bladder-cancers-are-treated

18. Inlexzo. Prescribing information. Johnson & Johnson; 2025. Accessed October 8, 2025. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INLEXZO-pi.pdf