Expert discusses how CREST, POTOMAC highlight trade-offs in NMIBC treatment

In this video, Daniel A. González Padilla, MD, a urologist with Clínica Universidad de Navarra in Madrid, Spain, discussed the clinical implications of recent trials evaluating immune checkpoint inhibitors combined with BCG therapy for patients with high-risk non–muscle-invasive bladder cancer (NMIBC), focusing on the CREST and POTOMAC studies and their impact on treatment decision-making.

In the CREST trial, investigators evaluated BCG induction and maintenance therapy combined with subcutaneous sasanlimab administered monthly for 2 years. The study demonstrated an absolute improvement of approximately 7% in high-grade recurrence-free outcomes compared with BCG alone. Notably, results appeared particularly favorable among patients with carcinoma in situ (CIS), a subgroup that is historically difficult to treat. Recurrence-free survival in this population reached about 90% at 3 years compared with 67% in the control arm. However, González Padilla emphasized caution in interpreting these findings because the trial included a relatively small number of CIS cases—roughly 50 patients per arm—raising the possibility that the observed benefit may partly reflect chance rather than a definitive effect.

The POTOMAC trial explored the addition of durvalumab (Imfinzi) to BCG therapy and provided insight into the potential synergy between intravesical immunotherapy and systemic immune checkpoint blockade. Adding durvalumab for 1 year alongside continued BCG maintenance produced a modest absolute benefit of 4.4%. Importantly, outcomes were poorest when durvalumab was used without sustained BCG maintenance, suggesting that checkpoint inhibition appears effective only when combined with ongoing BCG therapy. These findings reinforce the central role of BCG maintenance as the backbone of treatment.

Despite encouraging efficacy signals, González Padilla stressed that BCG alone already keeps roughly 75% of patients disease-free at 3 years, increasing to about 82% with added immunotherapy. However, approximately 25% of patients receiving checkpoint inhibitors experienced grade 3 or 4 immune-related adverse events, including life-threatening complications requiring hospitalization. Because recurrence still occurs in a substantial proportion of patients, clinicians must carefully balance modest efficacy gains against toxicity risks. He emphasized that shared decision-making is essential, as patients must weigh potential benefits against adverse effects and the possibility of ultimately requiring radical cystectomy or clinical trial participation.