Use of Rectal Diazepam to Prevent Bladder Spasms and Leakage of Medication During Intravesical Administration of Nadofaragene Firadenovec for Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer.

Abstract

Nadofaragene firadenovec-vncg is a US Food and Drug Administration-approved therapy for bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer. Bladder spasms and medication leakage during intravesical instillation are common and can affect treatment efficacy. We evaluated the effect of rectal diazepam pretreatment on bladder spasm incidence, retention of instilled medication, and 3-month recurrence rates. We retrospectively analyzed data from patients treated with nadofaragene firadenovec for bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer at Mayo Clinic from November 28, 2023, through September 30, 2024. Patients were stratified by pretreatment with rectal diazepam (10 mg) vs other strategies. Outcomes included bladder spasms, retention of instilled medication, and 3-month recurrence rates. Eighty-eight nadofaragene firadenovec instillations (45 patients) were evaluated. Rectal diazepam pretreatment was used for 25 instillations (28%) and associated with a 25% absolute risk reduction for nadofaragene firadenovec retention failure (4.0% vs 29% of instillations), as compared with other pretreatments (patient-level odds ratio, 0.22 [95% CI, 0.11-0.44]; <i>P</i> < .001). In addition, we observed a 24% absolute reduction in bladder spasm incidence (32% vs 56% of instillations) in the rectal diazepam group (patient-level odds ratio, 0.32 [95% CI, 0.13-0.82]; <i>P</i> = .02). Patients without medication leakage had a lower recurrence rate at 3 months (18% vs 38%), although this difference was not statistically significant (<i>P</i> = .3). One patient had fatigue attributable to rectal diazepam. Rectal diazepam pretreatment may reduce bladder spasms and improve nadofaragene firadenovec retention during intravesical instillation, thereby enhancing efficacy. Rectal diazepam could improve patient comfort and treatment outcomes, thus warranting further investigation through larger, prospective studies.