How immunotherapy and trials are redefining the treatment of bladder cancer

Neal D. Shore, MD, FACS

On April 26, 2025, Urology Times® hosted a Clinical Forum program during the American Urological Association 2025 Annual Meeting in Las Vegas, Nevada. During the event, experts in bladder cancer care discussed the evolving treatment landscape, highlighting innovations in intravesical therapies, systemic immunotherapy, and trial-driven strategies aimed at improving outcomes for patients with non–muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). The event was moderated by Neal D. Shore, MD, FACS, the medical director of START Carolinas, formerly the Carolina Urologic Research Center, in Myrtle Beach, South Carolina. What follows is a summary of this discussion.

This summary was generated by artificial intelligence and edited by humans for clarity.

This Clinical Forum event entailed a comprehensive overview of current issues, developments, and future directions in bladder cancer treatment, particularly emphasizing advancements in intravesical therapy, systemic treatment options, and clinical trial activity. The dialogue featured multiple experts sharing insights about both NMIBC and MIBC, highlighting the evolution of therapeutic strategies along with the challenges faced by clinicians.

One significant topic discussed was the emerging landscape of immunotherapy and targeted treatments for bladder cancer. The participants mentioned ongoing clinical trials investigating the efficacy of PD-1 inhibitors, such as pembrolizumab (Keytruda), in various settings including as a treatment modality for bladder cancer. Notably, there was mention of a trial incorporating PD-1 inhibitors into BCG therapy regimens, reflecting a move toward integrating systemic immune modulation with established intravesical therapies. This is seen as part of a broader shift aiming to improve outcomes in both BCG-responsive and BCG-unresponsive NMIBC, especially in patients who are not candidates for radical cystectomy.

The discussion referenced specific trials involving novel agents and delivery systems. Nadofaragene firadenovec-vncg (Adstiladrin) a form of gene therapy, and UGN-102, a reverse thermal gel formulation that enhances mitomycin dwell time, were cited as investigational options that expand the therapeutic arsenal. The mention of TAR-200, an intravesical device delivering chemotherapy directly into the bladder, underscored the focus on refining local treatment delivery. The pharmacological innovations seek to improve response rates while minimizing systemic toxicity and treatment burden. These agents and devices are evaluated as future options that could potentially change the standard of care, especially for patients with high-risk NMIBC or those with bladder-sparing preferences.

Clinical trials played a prominent role across the discussion, serving as the basis for many of the treatment strategies under consideration. Participants described how they handle trial recruitment in their practice settings, emphasizing the importance of multidisciplinary teams and navigators who review pathology reports and identify candidates for clinical study. There was an acknowledgment that although bladder cancer research has historically lagged behind other genitourinary malignancies, recent years have seen a significant increase in dedicated bladder cancer symposia, phase 3 trials, and novel therapeutic approaches. The expansion of research activity is framing a new era where bladder cancer is attracting greater clinical and academic attention.

The dialogue also touched on the nuances of bladder-sparing approaches vs traditional radical cystectomy. When discussing T2 disease involving location and tumor focus, participants considered factors such as patient comorbidities, bladder capacity, and patient preferences. The importance of systematic adherence to guidelines was acknowledged, although there was an understanding that practice variation exists, with some clinicians less stringent in following guidelines strictly and opting for individualized patient management.

Further, the discussion explored the complexities around defining BCG unresponsiveness and the importance of shared decision-making in NMIBC management. The role of multidisciplinary teams was emphasized, with urologic oncologists, medical oncologists, and other specialists collaborating to determine the best course for patients. It was recognized that in community settings, treatment may differ due to resource availability or familiarity with novel therapies, but the importance of multidisciplinary consultation remains a constant theme.

The issue of clinical trial selection and patient recruitment was also addressed. Experts noted that navigating the landscape of ongoing trials requires dedicated coordination, often involving pre-clinic meetings and careful case review. Such efforts aim to match patients with appropriate experimental therapies, including investigational agents targeting various molecular pathways. The overall tone suggested that active participation in clinical research is crucial for advancing bladder cancer treatment, and that the new surge of trials offers hope for better outcomes.

Finally, the speakers reflected on the progress made over recent years, especially since the resurgence of bladder cancer research following the introduction of checkpoint inhibitors around 2017 and 2018. The recognition of bladder cancer as an area of increasing research activity is illustrated by the volume of recent symposia, phase 3 trials, and innovative treatment modalities, contrasting with the previously limited attention afforded to this disease compared to prostate cancer. Overall, the discussion portrayed a field in transition, with ongoing trials and emerging therapies poised to reshape the management paradigm for bladder cancer, driven by a growing understanding of tumor biology and immune mechanisms.

In conclusion, the Clinical Forum underscored the importance of clinical trials and multidisciplinary collaboration in advancing bladder cancer care. Innovations such as intravesical drug delivery systems, gene therapies, and systemic immune checkpoint inhibitors are at the forefront, promising to improve outcomes and expand options for patients, especially those seeking bladder preservation. Despite the progress, challenges remain in standardizing practice, defining trial eligibility, and ensuring access across different practice settings. The conversation revealed a landscape poised for significant change, with ongoing research forming the backbone of future therapeutic breakthroughs.