Dr Lotan on the Future Research Directions in BCG-Unresponsive NMIBC

“This is a rapidly evolving field. We had [nogapendekin alfa inbakicept plus BCG] approved [for patients with NMIBC in 2024], we will probably have 2 new drugs approved in 2025, and maybe another the following year. [However,] we still have a lot to learn.”

Yair Lotan, MD, professor, urology, chief, urologic oncology, Jane and John Justin Distinguished Chair in Urology, UT Southwestern Harold C. Simmons Comprehensive Cancer Center; medical director, Urology Clinic, UT Southwestern and Parkland Health and Hospital System, discusses the evolving treatment paradigm for patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) and future research directions in this field.

Patients with BCG-unresponsive NMIBC often seek bladder-preserving alternatives to radical cystectomy, Lotan begins. This preference is particularly relevant for older and medically complex patients who face higher risks associated with major surgery, he explains. However, even younger, healthier patients frequently prioritize bladder preservation to maintain urinary and sexual function, Lotan notes.

Bladder-preserving NMIBC management strategies are advancing rapidly, Lotan emphasizes. In 2024, nogapendekin alfa inbakicept-pmln (Anktiva) received FDA approval for the treatment of patients with BCG-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ (CIS) with or without papillary tumors. He adds that there could be 2 additional BCG-unresponsive NMIBC drug approvals in 2025 and possibly more in subsequent years. Despite these advancements, most research in this disease has relied on single-arm trials rather than head-to-head comparisons, Lotan says. This limits the ability to draw definitive conclusions about the relative efficacy of new therapies, he explains. Challenges such as population heterogeneity, variations in treatment approaches, and diagnostic nuances in detecting CIS further complicate assessments, he notes.

Although the availability several treatment agents for patients with NMIBC represents a significant step forward, it is crucial for urologists to remain informed about emerging therapies and to discuss these options with patients, Lotan states. This shared decision-making approach empowers patients to make informed choices that align with their clinical and personal priorities, he concludes.