Botulinum toxin type A (BTX-A) has been shown to reduce incontinence and other symptoms of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO) and to improve quality of life [1-3]. The standard US FDA-label treatment protocol for BTX-A is injection at 20 sites x 0.5 mL (100 U) for OAB and 30 sites x 1.0 mL (200 U) for NDO. We hypothesized that utilizing fewer injection sites might improve safety, tolerability, and compliance without negatively impacting efficacy or reducing the interval between treatments.

In this pilot retrospective study, we reviewed records of patients with OAB or NDO who underwent intradetrusor injection of BTX-A in our center from January 2014 to September 2020. Due to the nature of the study design, obtaining ethical approval or informed consent was not a requirement. Initially, our patients were receiving 100 U of BTX-A in 10 mL of sterile saline, injected into 20 detrusor sites (the standard per-label treatment). Nonresponders underwent dose escalation. Soon after, our treatment protocol evolved to 100 U in 10 mL of saline at 3 intradetrusor sites and then to 100 U in 6 mL of saline at just 1 detrusor site. Briefly, our single-site procedure involves identifying a relatively avascular site of the mid posterior wall of the detrusor muscle, into which the mixture of BTX-A and saline is injected slowly.

The primary efficacy outcome was defined as improvement of >50% according to patient self-assessment 2 weeks after treatment. A second endpoint was the interval between treatment sessions; this was set at 6 months, but patients were allowed to shorten or extend the interval based on their response to therapy. Safety assessments entailed monitoring and evaluating adverse events, including urinary tract infections (UTIs), post-void residual volume, and clinically significant bleeding. In addition to evaluating treatment response, each assessment also included measuring post-void residual volume and performing urinalysis. Outcomes were analyzed by the number of injection sites, using mixed-level generalized linear models to account for repeat treatment of some patients.

Overall, 169 patients received BTX-A treatment of OAB or NDO during the study period. Patients whose treatment sessions consisted of 100 U of BTX-A were included in the analyses (n = 152). The mean age of the study population was 64 years, and all patients were female. Ninety-three percent had OAB (n = 142), and 7% had NDO (n = 10). There were 3 treatment sessions at 20 sites, 320 treatment sessions at 3 sites, and 27 treatment sessions at 1 site. The proportion of sessions for which patients reported improvement of >50% was 33% with the 20-site protocol, 93% with the 3-site protocol, and 85% with the single-site protocol. The mean intervals between treatments (± standard deviation [SD]) were 6.8 ± 0.2 months for the 3-site group and 7.3 ± 0.4 months for the single-site group, both of which are longer than the 6 months recommended for the traditional 20-site protocol. The primary efficacy endpoint (patient-reported improvement of >50%) did not differ significantly by the number of sites. There were no meaningful differences between the OAB and NDO groups with respect to efficacy or interval.

UTIs occurred in 67%, 11%, and 9% of the 20-site, 3-site, and 1-site treatment sessions, respectively (Figure 1). The number of injection sites per session correlated significantly with the incidence of UTI (P = .041) and with treatment interval (P = .032). Average post-void residual values (± SD) were 181 ± 127 mL, 109 ± 6 mL, and 93 ± 17 mL for the 20-site, 3-site, and 1-site cohorts, respectively (Figure 2). No patient required de novo catheterization. However, 1 patient in the 20-site cohort experienced bleeding that required catheterization and overnight hospitalization.

These findings indicate that using fewer injection sites per treatment session (1 or 3 sites rather than 20) does not reduce the efficacy of BTX-A therapy for OAB or NDO. Moreover, a longer treatment interval may be achievable with the 1- and 3-site regimens. Safety outcomes also appear superior, demonstrated by the lower incidence of UTI and smaller post-void residual volume with the 1- and 3-site regimens. Protocols with fewer injections per treatment have the potential to improve patient satisfaction and long-term compliance with treatment. Additional research is needed to confirm the findings.

There was no significant difference in efficacy between standard and modified BTX-A protocols for treatment of OAB or NDO. The incidence of adverse events (UTIs and elevated residuals) was significantly lower with fewer injection sites. No significant bleeding occurred among the 347 treatments in which a modified protocol was used. These data suggest that protocols with fewer injection sites have the potential to improve patient adherence to therapy by reducing the risk of bleeding, UTI, and discomfort, which ultimately may improve long-term patient satisfaction with BTX-A therapy. Adequately powered, randomized, controlled, multicenter studies are warranted to further explore the potential benefits of protocols that involve a reduced number of injection sites


Note: An abbreviated version of this abstract was presented at the Winter Meeting of the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction, February 25-27, 2021.

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