John Sfakianos, MD, on moving immunotherapy earlier in NMIBC treatment pathway

In a recent interview with Urology Times®, John P. Sfakianos, MD, outlined the scientific rationale for combining systemic immunotherapy with BCG in the BCG-naïve non–muscle invasive bladder cancer (NMIBC) setting. As he explains, the foundation for this approach dates back nearly 2 decades, with immunohistochemistry and gene expression studies demonstrating increased PD-1 and PD-L1 expression in high-risk, non–muscle invasive bladder tumors.

Sfakianos also noted, “The interesting part is that the percentage of expression is somewhere between 20% to 25%, which is basically what we see in the response rates when we're adding or using the systemic checkpoint therapy.” Sfakianos is a urologic oncologist in the department of urology at the Icahn School of Medicine at Mount Sinai in New York, New York.

The use of immune checkpoint inhibitors has been assessed in the BCG-unresponsive setting and is now moving into the BCG-naïve setting. By pairing systemic immunotherapy with BCG upfront, investigators are aiming to enhance immune activation, improve clinical outcomes, and potentially prevent or delay the development of treatment resistance.

Specifically, these combinations are being explored across 4 trials: CREST (sasanlimab plus BCG), POTOMAC (durvalumab plus BCG), ALBAN (atezolizumab plus BCG), and KEYNOTE-676 (pembrolizumab plus BCG). Significant results have been reported from both CREST and POTOMAC, but patient selection remains a key challenge.¹

REFERENCE
1. Gabriel PE, Horowitz A, Guerrero-Ramos F, et al. Therapeutic Intensification Based on Immune Checkpoint Inhibitors in Non-Muscle Invasive Bladder Cancer: State of the Art and Future Perspectives. Cancers (Basel). 2025;17(21):3555. doi:10.3390/cancers17213555