Bradley McGregor, MD, discusses BCG–immunotherapy data in high-risk NMIBC

BCG has long been the standard of care for patients with high-risk non–muscle invasive bladder cancer (NMIBC) based on pivotal data from more than 25 years ago demonstrating that induction followed by maintenance therapy reduces recurrence. However, historical outcomes also revealed significant limitations: approximately 30% of patients had persistent disease, and nearly 40% were considered BCG-refractory within the first few years. These shortcomings have driven efforts to improve outcomes beyond BCG alone.

In a recent interview with Urology Times®, Bradley McGregor, MD, discussed recent data on emerging treatment regimens in high-risk, BCG-naïve NMIBC. McGregor is a genitourinary medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts.

One promising strategy in this space has been the addition of immune checkpoint inhibitors to BCG, supported by evidence that PD-1/PD-L1 expression increases in BCG-refractory disease. This strategy is being explored in multiple phase 3 trials—namely ALBAN (NCT03799835), CREST (NCT04165317), and POTOMAC (NCT03528694).

Notably, CREST and POTOMAC included arms that replaced BCG maintenance with checkpoint inhibition. Both trials showed that this approach was inferior to standard BCG induction plus maintenance, underscoring the critical importance of maintenance BCG. When checkpoint inhibitors were added to both induction and maintenance BCG, results were mixed. ALBAN showed no benefit (hazard ratio, 0.98) in event-free survival,¹ while CREST and POTOMAC demonstrated more favorable hazard ratios (both, 0.68), translating to a 5% to 7% improvement in disease-free survival (EFS) at 3 years.^2,3

According to McGregor, differences in patient selection and BCG exposure likely contributed to these outcomes. ALBAN enrolled fewer patients with T1/Ta disease, more patients with CIS, and delivered fewer BCG instillations on average. Importantly, these findings do not appear to reflect differences in drug activity, as pembrolizumab and atezolizumab show comparable efficacy in CIS after BCG failure, McGregor explained.

Further, while checkpoint inhibition offers EFS gains, it also introduces substantial toxicity, with grade 3 or higher immune-related adverse events occurring in 10% to 30% of patients. Ultimately, these trials highlight both the durability of modern BCG therapy and the need for better biomarkers to identify patients most likely to benefit from intensified treatment strategies.

REFERENCES

1. Roupret M, Bertaut A, Pignot G, et al. ALBAN: A phase III, randomized, open-label international study of intravenous (iv) atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) vs BCG alone in BCG-naïve high-risk, non-muscle-invasive bladder cancer (NMIBC). Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA110. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA107.html.pdf

2. 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).

3. De Santis M, Palou J, Nishiyama H, et al. Durvalumab (D) in combination with Bacillus Calmette-Guérin (BCG) for BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC): Final analysis of the phase III, open-label, randomised POTOMAC trial. Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract LBA108. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA108.html.pdf