Comparative Neoplasm Risk of Mirabegron and Antimuscarinic Therapy in Overactive Bladder: A Multicenter Target Trial...

Background/Aims: Mirabegron, a selective β3-adrenergic receptor agonist used to treat overactive bladder (OAB), can promote adipose tissue browning and alter systemic metabolism, raising interest in its potential relationship with cancer development. However, clinical evidence regarding cancer risk remains limited and inconsistent. We compared the risks of obesity-related and site-specific cancers between patients with OAB initiating mirabegron and those initiating antimuscarinic medications. Methods: We conducted a multicenter emulated target trial using the TriNetX Global Collaborative Network. Adults aged ≥20 years with OAB or related symptoms who newly initiated mirabegron or an antimuscarinic medication were included using a new-user, active-comparator design. Patients with pre-existing malignancy were excluded. Propensity score matching was performed 1:1, and a 1-year lag period after treatment initiation was applied for cancer outcomes to reduce potential reverse causation from occult malignancy. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) under an intention-to-treat analog. Results: A 365-day lag/landmark period was applied before propensity-score matching. Patients with a recorded neoplasm or death during this period, or without follow-up extending through day 366, were excluded. Subsequent 1:1 propensity-score matching yielded 106,500 patients in each treatment group. Mirabegron initiation was not associated with the composite of obesity-related neoplasms compared with antimuscarinic initiation (HR, 1.011; 95% CI, 0.954-1.071). The individual neoplasm outcomes also showed no significant between-group differences. However, among patients eligible for the 1-year landmark mortality analysis, mirabegron initiation was associated with higher subsequent all-cause mortality (HR, 1.083; 95% CI, 1.044-1.124). Exploratory negative-control analysis of Hodgkin lymphoma showed no significant association. Conclusions: Among patients with OAB, mirabegron initiation was not associated with a significant difference in overall obesity-related neoplasm risk compared with antimuscarinic initiation. The observed associations with all-cause mortality should be interpreted cautiously given the observational design, multiple comparisons, and potential residual confounding. These findings are hypothesis-generating and require confirmation in prospective studies.