Bladder Cancer Takes Center Stage With Breakthrough Advancements at AUA 2025

The American Urological Association (AUA) 2025 Annual Meeting has kicked off, and for oncologists specializing in bladder cancer, several key presentations are offering compelling insights into potential shifts in treatment paradigms. Among the most eagerly awaited updates were findings from pivotal studies addressing both Bacillus Calmette Guérin (BCG)-naive and BCG-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC).

When asked about what the most exciting updates at AUA 2025, Jason Hafron, MD, CMO, chief medical officer and director of clinical research at Michigan Institute of Urology, highlights the phase 3 CREST study (NCT04165317) for managing BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC).¹ This randomized trial evaluated the addition of sasanlimab (PF-06801591), an anti–PD-1 monoclonal antibody, to the standard BCG induction and maintenance therapy.

Results showed that the combination significantly improved event-free survival (EFS), reducing the risk of high-grade recurrence, progression, persistent CIS, or death by an impressive 32% compared with BCG alone (HR 0.68; 95% CI, 0.49-0.94; 1-sided P = .0095). At the 24-month mark, nearly 85% of patients in the combination arm were event-free, a notable advantage over the approximately 80% in the BCG-only arm. This benefit persisted at 36 months, suggesting a durable impact of the combined approach.

For patients facing the challenge of BCG-unresponsive NMIBC, Mark D. Tyson, MD, MPH, a urologic oncologist at the Mayo Clinic in Phoenix, Arizona, highlights promising data from 2 distinct studies. The phase 3 BOND-003 trial (NCT04452591) focused on intravesical cretostimogene grenadenorepvec (CG0070) in patients with carcinoma in situ (CIS).² The results were encouraging, demonstrating a 75.5% complete response rate in the overall cohort (95% CI, 66.3%-83.2%; n = 83). Even at 12 and 24 months, a significant proportion of patients maintained this response, offering the potential for durable remission in a setting where treatment options are limited. The high local to central concordance in response assessments further bolsters the reliability of these findings.

Tyson also discusses cohort 2 of the phase 2b SunRISe-1 study (NCT04640623), which investigated TAR-200, an intravesical gemcitabine-releasing system.³ In patients with high-risk NMIBC, including those with CIS, who were ineligible for or refused radical cystectomy, TAR-200 demonstrated an exceptional 82.4% complete response rate (95% CI, 72.6-89.8). Importantly, over half of these responders maintained this response at 1 year without needing further treatment.

The median duration of response of nearly 26 months suggests a prolonged benefit (95% CI, 8.3-not estimable). Furthermore, the study reported a favorable safety profile, with predominantly low-grade urinary adverse events and a low rate of treatment discontinuation.

REFERENCES:

1. Shore ND, Powles T, Bedke J, et al. Sasanlimab in combination with Bacillus Calmette-Guérin improves event-free survival versus Bacillus Calmette Guérin as standard of care in high-risk non-muscle invasive bladder cancer: Phase 3 CREST study results. J Urol. 2025;213(5S).

2. BOND-003 Cohort C- phase 3, single-arm study of intravesical cretostimogene grenadenorepvec for high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ. J Urol. 2025;213(5S).

3. Necchi A, Daneshmand S, Simone G, et al. Practice-changing, Paradigm-shifting Clinical Trials in Urology: TAR-200 monotherapy in patients with bacillus Calmette-Guerin–unresponsive high-risk non–muscle-invasive bladder cancer carcinoma in situ: 1-year durability and patient-reported outcome. Presented at: 2025 American Urological Association Annual Meeting. April 26-29, 2025. Las Vegas, NV.