Optimizing Outcomes for High-Risk, Non-Muscle-Invasive Bladder Cancer with PD-(L)1 Inhibitors

Transurethral resection of bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) is the standard of care for high-risk, non-muscle-invasive bladder cancer (NMIBC). Despite its effectiveness, many patients face issues such as recurrence, progression, and intolerance to the treatment, highlighting the need for alternative options.

Recent clinical trials have focused on the use of Programmed cell death (ligand) 1 (PD-(L)1) inhibitors, which have shown clinical benefits in phase 1/2 trials for patients with BCG-unresponsive NMIBC. Preclinical and early clinical studies suggest that BCG upregulates PD-L1 expression in bladder cancer cells, and when combined with a PD-(L)1 inhibitor, a potent antitumor response is activated.

Several PD-(L)1 inhibitors are currently in phase 3 trials, exploring their efficacy in combination with BCG for BCG-naïve, high-risk NMIBC patients. The potential of these inhibitors is significant, but it is crucial to monitor for immune-related adverse events (irAEs) to ensure the safety and efficacy of the treatment.

Alternative administration routes, such as subcutaneous and intravesical, are being considered to facilitate adherence and access to treatment. The outcomes of combining PD-(L)1 inhibitors with BCG in NMIBC are highly anticipated, with a focus on addressing treatment resources, optimal management of irAEs, and the necessary education and training for clinical practice.

The exploration of PD-(L)1 inhibitors represents a promising direction in the treatment of high-risk NMIBC, offering hope for improved outcomes for patients facing this challenging condition.