Interventional procedure overview of botulinum toxin type A injection into the urethral sphincter for idiopathic chronic non-obstructive urinary retention

Efficacy summary

Success rate

In an RCT of 73 patients with medically refractory DV or DU comparing the effects of botulinum toxin type A (from now, botulinum) with normal saline urethral sphincter injections, there was an analysis of 62 patients who completed 1 month of follow up. This found that the overall success rate for both groups combined (defined as reduction of PPBC by more than or equal to 2) was 44%. Also, there was no statistically significant difference in success rate between patients who had botulinum injections and those who had saline placebo injections (37% [14/38] compared with 54%, [13/24], p= 0.114). Subgroup analysis showed that there was no statistically significant difference in success rate for the patients with DV (botulinum 44% [7/16] compared with placebo 68% [10/15], p= 0.200) and the patients with DU (botulinum 32% [7/22] compared with placebo 33% [3/9], p=0.935). The success rates after a second botulinum injection increased from 29% to 57% among patients with DV and from 25% to 50% among patients with DU (Jiang 2016).

In a case series of 27 patients with idiopathic low detrusor contractility treated with botulinum injection into the urethral sphincter, there was an overall success rate was 89% (24/27; Kuo 2007a).

In a case series of 66 patients who had 50 units (n=33) and 100 units (n=33) of botulinum into the urethral sphincter, there was no statistically significant difference in the overall success rate between the 2 doses (85% [28/33] compared with 91% [30/33], p=0.452; Kuo 2007b).

In a retrospective case series of 81 patients with non-neurogenic DV (55 with midurethral DV, 19 with distal urethral DV, and 7 with bladder neck dysfunction and midurethral DV), treated with botulinum injection into the urethral sphincter, the treatment was successful in 68% (55/81) of patients and failed in 32% (26/81) of patients. Treatment success was defined as an improvement of VE by 10% and patient-reported global response assessment by more than or equal to 1% (Jiang 2021).

Clinical outcomes

IPSS

In the RCT analysis of 62 patients, statistically significant improvements from baseline in IPSS-V, IPSS-S, IPSS-T were seen in the botulinum injection and placebo groups after first EUS injections at 1-month follow up (p<0.05). Patients who had botulinum injections had statistically significantly less improvement in IPSS-V, IPSS-S and IPPS-T than patients in the placebo group. Subgroup analysis showed that the outcomes were similar between the DV and DU groups after first injection. There was a statistically significantly greater reduction in IPSS-T in the placebo group than in the botulinum group in patients with DV (p= 0.026). In patients with DU, the placebo group had statistically significantly greater reductions in IPSS-V and IPSS-T than the botulinum group (p=0.036 and 0.002). Repeated botulinum injection into the urethral sphincter in the botulinum group (n=19) resulted in improvement in IPSS-V, IPSS-S, IPSS-T in patients with DV and DU (Jiang 2016).

In a case series of 10 patients with a primary disorder of urethral sphincter relaxation (Fowler's syndrome) treated with 100 units of botulinum injection into the external urethral sphincter, the mean symptom scores on the IPSS questionnaire improved from 25.6 to 14.1. Also, the mean 'bother' score on IPSS reduced from 6.1 to 3.5 at 10-week follow up (Panicker 2016).

PPBC

In the RCT analysis of 62 patients, statistically significant improvements from baseline were seen in both botulinum and placebo groups at 1-month follow up after first injection (p<0.05). Repeated botulinum injections into the urethral sphincter in the botulinum group (n=19) resulted in improvement in PPBC in patients with DV and DU (Jiang 2016).

In a retrospective analysis of 56 patients with refractory idiopathic external urethral sphincter dysfunction who had botulinum injections into the external urethral sphincter, patients with DV (n=23) had no statistically significant differences in treatment improvement rates compared with patients with PRES (n=33). The rates of good subjective outcomes (65% [15/23] compared with 64% [21/33], p=0.903) and objective outcomes (74% [17/23] compared with 67% [22/33], p=0.562) were not statistically significantly different between the 2 groups at 1-month follow up (Ou 2021).

Recovery of detrusor function

In the case series of 27 patients, there was recovery of detrusor contractility in 48% (13/27) of patients (7 with DV and low detrusor contractility with concomitant PRES, 3 with DHIC and 3 with DU) and no recovery in 52% (14/27) of patients. Detrusor contractility recovery was defined as an increase in Pdet and Qmax and reduced PVR volume). Patients with recovery could void without abdominal straining, but patients without recovery continued to void with increased abdominal pressure (Kuo 2007).

Duration of treatment effect

In the case series of 27 patients, patients with recovery of detrusor contractility (n=13) had a statistically significantly longer duration of treatment effect than those without recovery (n=14; 14±7.6 months compared with 4.6±2.5 months, p<0.001; Kuo 2007).

In the case series of 66 patients, the mean duration of treatment effect was statistically significantly shorter in the 50 units botulinum injection group than the 100 units group (6.4±3.6 months compared with 8.4±3.4 months, p= 0.022; Kuo 2007b)

QOL

In the RCT analysis of 62 patients, QOL statistically significantly improved from baseline in both botulinum injection and placebo groups at 1-month follow up after first injection (botulinum group from 4.5±1.9 to 3.0±1.9 and placebo group from 5.4±0.9 to 2.4±1.9, p<0.05 compared with baseline or before injection). Compared with placebo, botulinum injection into the urethral sphincter resulted in statistically significantly less improvement in QOL (p<0.01 between the groups after treatment). Repeated botulinum injection into the urethral sphincter (n=19) resulted improvement in QOL index in patients with DV and DU (p<0.05; Jiang 2016).

In the case series of 27 patients, 10 out of 13 patients with recovery of detrusor contractility had an excellent outcome. QOL index assessed using a questionnaire (with a scale ranging from 0 to 6) improved by more than 2 points and reduction in PVR by more than 50%. Three patients had an improved outcome (QOL index improved by 1 point with improvement of urodynamic parameters). Of these who reported no recovery (n=14), 1 had an excellent outcome, 10 had an improved result and 3 had a failed result (no improvement in QOL; Kuo 2007).

In the case series of 66 patients with voiding dysfunction (of any aetiology) treated with botulinum injection into the external urethral sphincter (100 units and 50 units), the overall treatment results were excellent in 61% (20/33) and 70% (23/33) of patients respectively. 'Excellent' was defined as a more than 2-point improvement in the QOL index, 50% or more reduction in PVR and 25% or more reduction in MUCP. The overall treatment results were improved in 30% (10/33) and 15% (5/33) of patients respectively. 'Improved' was defined as an improvement in the QOL index of 1 point, 50% or more reduction in PVR or 25% or more reduction in MUCP. Treatment failed in 9% (3/33) and 15% (5/33) patients respectively. 'Failed' was defined as no improvement in QoL regardless of the urodynamic improvement (Kuo 2007b).

Urodynamic parameters

In the RCT analysis of 62 patients, after first injections in both groups, there was a statistically significant increase (p<0.05) in Qmax (botulinum group from 5.3±5.7 to 9.8±9.5 and placebo group from 6.3±5.1 to 9.5±6.6) and in VE (botulinum group from 29.6±28.3 to 44.1±35.3 and placebo group from 34.4 ±34.2 to 56.1±36.4). But there was only a statistically significant improvement in VV in the botulinum group (from 119.9±82.2 ml to 191.0±140.1 ml) and only a statistically significant improvement in PVR in the placebo group (from 279.3±246.9 to 146.6±160.5, p<0.05). There were no statistically significant differences in changes in the other VUDS parameters (Pdet cm/H₂0, CBC) between the botulinum and placebo groups after the first injection. Subgroup analysis showed that, in patients with voiding dysfunction (n=31), there were only statistically significant improvements in VUD parameters in the botulinum group, including Pdet (from 40.3±23.0 cmH₂O to 31.6±22.3 cmH₂O), Qmax (from 6.4±5.4 ml/sec to 11.1±10.1 ml/sec) and VV (from 119.9±82.2 ml to 191.0±140.1 ml). In patients with DU (n=31), there were statistically significant improvements in Qmax in both groups (botulinum group from 4.5±6.0 ml/sec to 8.8±9.1 ml/sec, and placebo group from 3.4±3.7 ml/sec to 10.6±9.2 ml/sec) and VE (botulinum group from 20.8±28.5 to 39.4±36.0 and placebo group from 17.0±31.5 to 61.6±40.7). In the DU group, reduction in PVR, was statistically significantly greater in the placebo group (from 415.0±304.0 ml to 131±169.1 ml) than in the botulinum group (from 350.0±174.6 ml to 293±233.1 ml, p=0.046 between the groups after treatment). There were no statistically significant changes in VUD parameters after repeated botulinum injections (Jiang 2016).

In the case series of 27 patients, there was a statistically significant reduction in the PVR (from 328±134 ml to 31±35 ml, p<0.05 compared with baseline or before injection) and a statistically significant increase in the Qmax (from 4.7±5.6 ml/sec to 13±6.6 ml/sec, p<0.05 compared with baseline or before injection) in patients with and without recovery of detrusor contractility after urethral injections of botulinum . Pdet statistically significantly reduced (from 47±39 cmH20 to 32±27 cmH20, p<0.05 compared with baseline or before injection) in patients without recovery but statistically significantly increased it in patients with recovery (from 7.4±9.2 cmH20 to 24±13.1 cmH20, p<0.05 compared with baseline) (Kuo 2007).

In the case series of 66 patients, there were statistically significant reductions in urodynamic parameters (Pdet, PVR, MUCP), and a statistically significant increase in Qmax with both doses of botulinum (50 units and 100 units) after treatment compared with baseline. But no statistically significant differences were noted between groups after treatment (Kuo 2007b).

In the case series of 10 patients, with 100 units of botulinum injection into the urethral sphincter, there was an improvement in Qmax (from 8.12 ml/sec to 15.8 ml/sec), a decrease in PVR (from 260 ml to 89 ml) and an improvement in the mean static UPP (from 113 cmH₂O to 90 cmH₂O), at 10-week follow up (p value not assessed; Panicker 2016).

In the retrospective case series of 81 patients with DV, patients with a successful treatment outcome after botulinum injection into the urethral sphincter had a statistically significant change in urodynamic parameters (decrease of Pdet, PVR volume and bladder outlet obstruction index, and an increase in VE) at follow up compared with the treatment failure group (Jiang 2021).

In the retrospective analysis of 56 patients, for both patients with DV (n=23) and patients with PRES (n=33), botulinum injections into the EUS resulted in statistically significantly improved Qmax (DV: 7.3 to 10.2 ml/sec, p<0.01; PRES: 7.4 to 10.2 ml/sec, p<0.05) and VE (DV: 0.47 to 0.59 ml/sec, p<0.01; PRES: 0.43 to 0.60 ml/sec, p<0.01) after the injections. Also, there was a statistically significant decrease in FS (p=0.023), US (p=0.004) and CBC (p=0.044 in the DV group than the PRES group after the injections (Ou 2021).