Emerging bladder-sparing treatments for high risk non-muscle invasive bladder cancer

Bladder cancer (BC) is a significant global health concern, with non-muscle invasive bladder cancer (NMIBC) comprising 75% of cases at diagnosis. High-risk NMIBC (HR-NMIBC) poses a significant therapeutic challenge due to its high recurrence and progression rates despite Bacillus Calmette-Guerin (BCG) therapy. Radical cystectomy remains the gold standard for BCG-unresponsive cases but is often met with considerable morbidity and patient reluctance. This has driven research into alternative bladder-sparing therapies (BSTs). Emerging BSTs include immune checkpoint inhibitors like pembrolizumab and novel agents such as nadofaragene firadenovec and nogapendekin alfa inbakicept (IL-15). These therapies have demonstrated promising response rates in clinical trials, offering potential for disease management while preserving bladder function. Gene therapies and targeted agents like CG0070 and EG-70 are also gaining traction for their innovative mechanisms. However, most data are derived from early-phase, single-arm studies, necessitating larger, randomised trials for validation. Device-assisted strategies, including hyperthermic and electromotive drug delivery systems, show potential to enhance intravesical therapy efficacy. Despite advancements, challenges remain in balancing efficacy, safety, and cost-effectiveness within diverse healthcare settings. This narrative review highlights the evolving landscape of BSTs for HR-NMIBC, emphasising the need for robust clinical evidence to refine patient selection and optimise outcomes.