This is the first time a combination of surgical therapies was applied to treat mixed urinary incontinence (MUI). In a single operation, Botulinum toxin (Botox®) and bulking agent (polyacrylamide hydrogel, PAHG, Bulkamid®) were injected against the urgency (UUI) and stress (SUI) components of MUI. An elderly and frail population group may benefit from the short intervention that – in contrast to conservative and medical treatments – does not require a long-term therapy adherence. Conversely, such a combination therapy may carry the risk of potentiating adverse events, e.g. postoperative voiding dysfunction, urinary tract infection or de novo urgency. To find out, we prospectively investigated safety, efficacy and sustainability of this novel combination approach in a small study population.

This prospective, investigator-initiated observational trial was conducted at a single tertiary urogynecological center. Fifty-five women with therapy-refractory, stress-dominant MUI were treated with botulinum toxin (median 50 units) and PAHG (median 2.0 ml) in one surgical procedure. UUI and SUI parameters were separately assessed after 4 and 12 months and MUI outcome was calculated by combining UUI and SUI outcomes. Objective cure was defined by no UUI episode/24 h for UUI and a negative cough test for SUI. Subjective cure of UUI or SUI was defined by a UUI-VAS or SUI-VAS score reduction of ≥90% (describing the improvement of quality of life), or by an ICIQ-UI SF score ≤5 (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form). Complications were monitored throughout the study. Continuous data were analyzed by the paired Wilcoxon signed-rank test with significance level 0.05.

Patients’ median age was 75 years, the median body mass index was 28.5 kg/m2. Twenty-two percent had one, 64% had two or more severe comorbidities. Fifty-six percent had a previous incontinence surgery and 44% a previous prolapse surgery. A general anesthesia or the discontinuation of anticoagulation was not necessary. For UUI, SUI and MUI, objective cure rates were 53%, 73% and 42%, and subjective cure rates were 52%, 71% and 50% at 4 months. At 12 months, objective cure rates were 56%, 73% and 50%, and subjective cure rates were 42%, 78%, and 40%. Subjective cure determined by ICIQ-UI SF was 60% at 4 months and 47% at 12 months. The median ICIQ-UI SF score improved from 15.4 at baseline to 4.8 and 5.5 at the 4 and 12-month follow-ups. All follow-up values were significantly different from baseline (p <0.001). All complications were transient and included 22% clean intermittent catheterization immediately after surgery, 33% post-void residual volumes >100 ml at 14 days, and 13% symptomatic urinary tract infections within the first postoperative month.

Outcome was similar or even better than in other PAHG studies. None of the patients required a repeat injection within the 12-month follow-up period. This was a significant difference from other studies where 8%-77% required a reinjection (1). We assume that the novel PAHG injection technique with 4 instead of 3 depots at the same level of the urethra made a significant contribution to the long-term success by stabilization of the bladder neck. – The botulinum toxin effect was also similar or better than in other studies. Only 4% of the patients required a second botulinum toxin injection prior to the 12-month visit, compared to 71.5% who wanted a repeat injection within the first postoperative year (2). Thus, the botulinum toxin effect lasted longer than the previously published 4 to 10 months. The combination with PAHG could be responsible for this long-term success. We hypothesize that the PAHG depots prevented urethral funneling and blocked the entrance of urine into the proximal urethra. Consequently, trigger points in the bladder neck were not stimulated, and the sensation of “urgency” was not elicited. – The urinary retention rate due to PAHG was higher than in other studies (1). However, this must not be a disadvantage, since also other clinicians found an association between transient postoperative urinary retention and a successful outcome. High residual urine volumes two weeks after botulinum toxin injection were also transient and comparable to other studies with botulinum toxin therapy (3). Symptomatic urinary tract infections in the first postoperative month were slightly higher than after PAHG therapy alone (1), but similar to after botulinum toxin therapy alone (2,3). All urinary tract infections were uncomplicated and without upper urinary tract involvement.

The new combination therapy of MUI with botulinum toxin and PAHG was effective, sustainable and safe with great advantages for the examined patient group. In particular, frail, elderly and multimorbid patients after unsuccessful incontinence surgery (salvage population) or patients with other previous urogynecological operations benefit from this single short procedure without general anesthesia and without discontinuation of anticoagulation.

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