2026 AUA North Central Section Meeting: Updates in high-risk NMIBC

In this interview, Paras H. Shah, MD, a urologic oncologist at Mayo Clinic in Rochester, Minnesota, recaps bladder cancer research and clinical developments presented at the 2026 North Central Section Annual Meeting, with a focus on high-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). This interview was initially live streamed on the Urology Times® X account.

Shah discusses how the expanding availability of bladder-preserving therapies has created alternatives to radical cystectomy, although he emphasizes that cystectomy remains an important treatment option, particularly for patients who experience recurrence after salvage therapy or have disease with a higher risk of progression. He also addresses how the ongoing BCG shortage has contributed to an emerging population of BCG-exposed or BCG-experienced patients who may not meet established criteria for BCG-unresponsive disease but could benefit from clinical trial enrollment.

A key focus of the discussion is Shah's presentation of cystectomy-free survival and safety findings from cohort C of the phase 3 BOND-003 trial (NCT044552591), evaluating investigational cretostimogene grenadenorepvec in patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ.¹ He highlights cystectomy-free survival rates of 89.2% (95% CI, 81.3 to 93.9) at 12 months and 81.3% (95% CI, 71.8 to 87.8) at 24 months, noting that most patients (83.3%) who ultimately underwent cystectomy had non-muscle-invasive disease at the time of surgery. He also discusses the treatment's safety profile, including the absence of grade 3 or higher treatment-related adverse events in the cohort.

Additionally, Shah reviews the ongoing LEGEND trial (NCT04752722), which is evaluating the investigational nonviral gene therapy detalimogene voraplasmid (EG-70) in high-risk NMIBC.² He describes its mechanism of action, potential practical advantages related to drug handling and administration, and the distinct patient populations being evaluated in cohorts 2A and 3, including BCG-naïve patients with carcinoma in situ and patients with BCG-unresponsive papillary-only disease.

Looking ahead, Shah anticipates that treatment selection and sequencing for BCG-unresponsive NMIBC will become increasingly individualized as more therapies become available. He notes that the absence of head-to-head comparisons makes it difficult to establish the relative efficacy of currently available and investigational agents, meaning treatment decisions will likely reflect several factors beyond clinical outcomes, including treatment schedules, patient preferences, drug costs, and practice-level administration considerations.

Reflecting on the broader discussions and data presented at the 2026 North Central Section meeting, Shah emphasizes that advances in bladder preservation should not diminish the role of BCG or radical cystectomy. Although he expects additional options to emerge across BCG-unresponsive, BCG-naïve, and BCG-exposed disease over the next several years, he underscores the importance of discussing cystectomy when repeated bladder-preserving treatments may compromise patients' quality of life or fail to adequately control disease.

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REFERENCES

1. Tyson M, Joshi S, Shah P, et al. CYSTECTOMY-FREE SURVIVAL FOLLOWING CRETOSTIMOGENE GRENADENOREPVEC IN HIGH-RISK BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER WITH CARCINOMA IN SITU: RESULTS FROM THE PHASE 3 BOND-003 TRIAL (COHORT C). Presented at: 100th Annual Meeting of the North Central Section of the AUA. October 14 - 17, 2026. Wailea, HI. Poster 129

2. Shah PH, Guerrero-Ramos F, Manuel de la Morena Gallego J, et al. INTRAVESICAL DETALIMOGENE VORAPLASMID FOR HIGH-RISK (HR) NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC): LEGEND COHORTS 2A AND 3 TRIAL IN PROGRESS. Presented at: 100th Annual Meeting of the North Central Section of the AUA. October 14 - 17, 2026. Wailea, HI. Poster 230