Victor W. Nitti

Fourth international consultation on incontinence recommendations of the international scientific committee: Evaluation and treatment of urinary incontinence, pelvic organ prolapse, and fecal incontinence†‡§¶‖

P. Abrams , K.E. Andersson, L. Birder, L. Brubaker, L. Cardozo, C. Chapple, A. Cottenden, W. Davila, D. de Ridder, R. Dmochowski, M. Drake, C. DuBeau, C. Fry, P. Hanno, J. Hay Smith, S. Herschorn, G. Hosker, C. Kelleher, H. Koelbl, S. Khoury,* R. Madoff, I. Milsom, K. Moore, D. Newman, V. Nitti, C. Norton, I. Nygaard, C. Payne, A. Smith, D. Staskin, S. Tekgul, J. Thuroff, A. Tubaro, D. Vodusek, A. Wein, and J.J. Wyndaele and the Members of the Committees

DIAGNOSING BLADDER OUTLET OBSTRUCTION IN WOMEN

PURPOSE There are no universally accepted urodynamic criteria for diagnosing female bladder outlet obstruction. When accepted criteria for men are applied to women, the diagnosis of obstruction may often be missed, which is most likely due to differences in voiding dynamics. We propose video urodynamic criteria for diagnosing obstruction in women, and describe the urodynamic findings in those with and without obstruction. MATERIALS AND METHODS We reviewed the charts of 331 women who underwent multichannel video urodynamics for nonneurogenic voiding dysfunction. Of these women 261 (mean age 55.8 years) had evaluable voiding pressure flow studies with simultaneous video fluoroscopy of the bladder outlet during voiding. At video urodynamics cases were classified as obstructed if there was radiographic evidence of obstruction between the bladder neck and distal urethra in the presence of a sustained detrusor contraction. Strict pressure flow criteria were not used. Maximum flow rate, detrusor pressure at maximum flow rate, post-void residual, bladder capacity and the incidence of detrusor instability were compared between obstructed and unobstructed cases. RESULTS A total of 76 women met the criteria for obstruction (mean age 57.5 years), while 184 (mean age 55) did not. Causes of obstruction were dysfunctional voiding in 25 cases, cystocele in 21, primary bladder neck obstruction in 12, iatrogenic from incontinence surgery in 11, urethral stricture in 3, uterine prolapse in 2, urethral diverticulum in 1 and rectocele in 1. Obstructed cases had lower mean maximum flow rate (9 versus 20.2 ml. per second, p <0.0001), higher mean detrusor pressure at maximum flow rate (42.8 versus 22.1 cm. water, p <0.0001) and higher mean post-void residual (157 versus 33 ml., p <0.0001). There was no difference in bladder capacity (381 versus 347 ml.) or incidence of detrusor instability (45 versus 41%). CONCLUSIONS Using the proposed video urodynamic criteria obstructed cases had significantly higher voiding pressures, lower flow rates and higher post-void residual than unobstructed cases, as expected. However, absolute values, especially for voiding pressure, are not as dramatic in women as in men. Pressure flow studies alone may fail to diagnose obstruction but simultaneous imaging of the bladder outlet during voiding greatly facilitates diagnosis.

Efficacy and Safety of OnabotulinumtoxinA for Idiopathic Overactive Bladder: A Double-Blind, Placebo Controlled, Randomized, Dose Ranging Trial

PURPOSE Treatment options for patients with overactive bladder refractory to anticholinergics are limited. We assessed the dose response across a range of doses of onabotulinumtoxinA (BOTOX®) in patients with idiopathic overactive bladder and urinary urgency incontinence whose symptoms were not adequately managed with anticholinergics. MATERIALS AND METHODS In a phase 2, multicenter, randomized, double-blind study, 313 patients with idiopathic overactive bladder and urinary urgency incontinence experiencing 8 or more urinary urgency incontinence episodes a week and 8 or more micturitions daily at baseline received 50, 100, 150, 200 or 300 U intradetrusor onabotulinumtoxinA, or placebo. Symptoms were recorded using a 7-day bladder diary. The primary efficacy variable was weekly urinary urgency incontinence episodes and the primary end point was week 12. RESULTS Demographics and baseline characteristics were balanced across the treatment groups. Durable efficacy was observed for all onabotulinumtoxinA dose groups of 100 U or greater for primary and secondary efficacy measures, including the proportion of incontinence-free patients. When the dose response curves were analyzed, doses greater than 150 U contributed minimal additional or clinically relevant improvement in symptoms. This finding was also reflected in health related quality of life assessments. Dose dependent changes in post-void residual urine volume were observed and the use of clean intermittent catheterization was also dose dependent. The only adverse events significantly greater with onabotulinumtoxinA than with placebo were urinary tract infection and urinary retention. CONCLUSIONS OnabotulinumtoxinA at doses of 100 U or greater demonstrated durable efficacy in the management of idiopathic overactive bladder and urinary urgency incontinence. A dose of 100 U may be the dose that appropriately balances the symptom benefits with the post-void residual urine volume related safety profile.

Results of a Randomized Phase III Trial of Mirabegron in Patients with Overactive Bladder

PURPOSE Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects. Mirabegron, a β3-adrenoceptor agonist, may offer an effective and well tolerated alternative treatment for overactive bladder. MATERIALS AND METHODS A randomized, double-blind, placebo controlled trial was conducted in the United States and Canada. After a 2-week placebo run-in period, adults with overactive bladder symptoms for 3 or more months were randomized 1:1:1 to receive placebo, 50 or 100 mg mirabegron once daily for 12 weeks. Efficacy data were collected via patient completed diaries and quality of life assessments. Co-primary efficacy end points were changes from baseline to final visit in mean number of incontinence episodes per 24 hours and micturitions per 24 hours. Key secondary micturition and incontinence end points were also evaluated. Safety assessments included treatment emergent adverse events, laboratory assessments, vital signs, electrocardiograms and post-void residual volume. RESULTS Compared to placebo, 50 and 100 mg mirabegron groups demonstrated statistically significantly greater mean decreases (95% CI) from baseline for incontinence episodes (-1.13 [-1.35, -0.91], -1.47 [-1.69, -1.25] and -1.63 [-1.86, -1.40]) and micturitions (-1.05 [-1.31, -0.79], -1.66 [-1.92, -1.40] and -1.75 [-2.01, -1.48]) per 24 hours (p <0.05). Significant improvements in all key secondary end points were observed for both mirabegron doses vs placebo. The incidence of frequently reported treatment emergent adverse events (hypertension, urinary tract infection, headache, nasopharyngitis) was similar in the mirabegron and placebo groups. Dry mouth was reported for 1.5%, 0.5% and 2.1% of patients in the placebo, 50 and 100 mg mirabegron groups, respectively. CONCLUSIONS Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects.

The etiology of post-radical prostatectomy incontinence and correlation of symptoms with urodynamic findings.

PURPOSE We evaluated men with post-radical prostatectomy incontinence to determine the incidence of intrinsic sphincter deficiency and bladder dysfunction, and the contribution of each to incontinence. In addition, we determined if subjective symptoms of stress urinary incontinence and urge incontinence correlated with urodynamic findings of intrinsic sphincter deficiency and bladder dysfunction, respectively. MATERIALS AND METHODS A total of 60 consecutive patients (mean age 64.8 years) were prospectively evaluated with multichannel video urodynamics. All patients were evaluated at least 6 months postoperatively and had achieved a stable level of continence. Patients characterized incontinence as stress or urge related, and stress urinary incontinence was graded from 0 to 3. Intrinsic sphincter deficiency was defined as incontinence associated with increased intraabdominal pressure and was further assessed by Valsalvas leak point pressure. Bladder dysfunction included urodynamic findings of detrusor instability or decreased compliance. RESULTS Intrinsic sphincter deficiency was demonstrated in 54 patients (90%). Some component of bladder dysfunction was seen in 27 patients (45%), including detrusor instability in 24 and decreased compliance in 3, but incontinence was actually a result of bladder dysfunction in only 16 (27%). Incontinence was due to intrinsic sphincter deficiency alone in 40 patients (67%), intrinsic sphincter deficiency and bladder dysfunction in 14 (23%), and bladder dysfunction alone in only 2 (3%). Incontinence was not demonstrated on video urodynamics in 4 patients (7%). Of the 57 men who complained of stress urinary incontinence 54 demonstrated intrinsic sphincter deficiency for a positive predictive value of 95%. The 3 patients without stress urinary incontinence did not demonstrate intrinsic sphincter deficiency for a negative predictive value of 100%. Positive and negative predictive values for urge incontinence were 44 and 81%, respectively. CONCLUSIONS Incontinence after radical prostatectomy is associated with intrinsic sphincter deficiency in the overwhelming majority of patients. Bladder dysfunction rarely is an isolated cause. When present on urodynamic tests bladder dysfunction may not always be a significant contributor to incontinence. The symptom of stress urinary incontinence (or its absence) accurately predicts the finding (or absence) of intrinsic sphincter deficiency on urodynamics. Urge incontinence is not as reliable in predicting incontinence due to bladder dysfunction.

OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial

Purpose: Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics. Materials and Methods: Eligible patients with overactive bladder, 3 or more urgency urinary incontinence episodes in 3 days and 8 or more micturitions per day were randomized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100 U or placebo. Co‐primary end points were the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a positive response on the treatment benefit scale at posttreatment week 12. Secondary end points included other overactive bladder symptoms and health related quality of life. Adverse events were assessed. Results: OnabotulinumtoxinA significantly decreased the daily frequency of urinary incontinence episodes vs placebo (−2.65 vs −0.87, p <0.001) and 22.9% vs 6.5% of patients became completely continent. A larger proportion of onabotulinumtoxinA than placebo treated patients reported a positive response on the treatment benefit scale (60.8% vs 29.2%, p <0.001). All other overactive bladder symptoms improved vs placebo (p ≤0.05). OnabotulinumtoxinA improved patient health related quality of life across multiple measures (p <0.001). Uncomplicated urinary tract infection was the most common adverse event. A 5.4% rate of urinary retention was observed. Conclusions: OnabotulinumtoxinA 100 U showed significant, clinically relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated.

Contemporary Management of Postprostatectomy Incontinence

CONTEXT In recent years, despite improvement in the surgical technique, the prevalence of postprostatectomy incontinence has increased due to a rise in the number of radical prostatectomies performed annually. OBJECTIVE The aim of this review is to evaluate contemporary noninvasive and invasive treatment options for postprostatectomy incontinence. EVIDENCE ACQUISITION In August 2010, a review of the literature was performed using the Medline database. EVIDENCE SYNTHESIS All articles concerning noninvasive and invasive treatment for postprostatectomy incontinence were included. CONCLUSIONS No randomised controlled trials exist to compare currently used noninvasive and invasive treatments for postprostatectomy incontinence. Pelvic floor muscle training is recommended for the initial treatment of stress urinary incontinence (SUI). Additionally, antimuscarinic therapy should be applied for urgency or urge incontinence. For decades, the artificial urinary sphincter was the reference standard for persistent SUI. Nowadays, male slings are an alternative for men with mild to moderate postprostatectomy SUI.

Correlation of Valsalva Leak Point Pressure with Subjective Degree of Stress Urinary Incontinence in Women

PURPOSE We correlated symptoms of stress urinary incontinence in women with intrinsic urethral function, as measured by Valsalva leak point pressure. In addition, we assessed the effects of urethral hypermobility, baseline resting abdominal pressure, patient age and menopausal status on Valsalva leak point pressure. MATERIALS AND METHODS We evaluated 64 consecutive women (mean age 50 years, range 20 to 79) with complaints of stress urinary incontinence. Initially the patient history was obtained and the subjective degree of stress urinary incontinence was graded as 1, 2 or 3 according to the SEAPI-QMN classification. Multichannel video urodynamics were then performed. At a volume of 150 to 200 ml. (or half bladder capacity when functional capacity was less than 150 ml.) filling was stopped. Resting, coughing and progressive Valsalva maneuvers were performed to determine Valsalva leak point pressure and the presence of urethral hypermobility. Valsalva leak point pressure was defined as the minimum total vesical pressure required to cause urinary incontinence in the absence of a detrusor contraction. Urodynamics were completed and detrusor instability or stress induced instability was noted. RESULTS Of the 64 women 52 (81.3%) had stress urinary incontinence. The exact test for trend demonstrated a statistically significant difference in the number of patients with a Valsalva leak point pressure of 90 cm. water or less (p = 0.0002) and 60 cm. water or less (p = 0.0002) among the 3 symptom groups. There was no correlation between Valsalva leak point pressure and resting vesical (which equals abdominal) pressure, patient age or menopausal status, or urge incontinence or detrusor instability among the 3 groups. CONCLUSIONS The subjective degree of stress urinary incontinence can predict intrinsic urethral function as measured by Valsalva leak point pressure. Higher grades of stress urinary incontinence have a higher likelihood of a low Valsalva leak point pressure. Many women with grade 2 or 3 stress urinary incontinence have a Valsalva leak point pressure of 90 cm. water or less despite urethral hypermobility and they may have a component of intrinsic urethral deficiency.

Artificial Urinary Sphincter Versus Male Sling for Post-Prostatectomy Incontinence—What Do Patients Choose?

PURPOSE Early outcomes of the male sling to correct post-prostatectomy incontinence have been promising in select patients. Long-term data are lacking to determine whether the male sling is as effective as the artificial urinary sphincter, which is the current gold standard. Because the male sling offers the significant advantage of avoiding a mechanical device but without established success, we determined the patient preference for the male sling vs the artificial urinary sphincter. MATERIALS AND METHODS We reviewed the charts of 133 men with post-prostatectomy incontinence who underwent the first procedure to correct incontinence. After urodynamics the surgeon recommended an artificial urinary sphincter or a male sling and patients were told the artificial urinary sphincter satisfaction rate and shorter term data on the male sling. Patients with high grade post-prostatectomy incontinence (pad weight greater than 400 gm/24 hours) were recommended to receive an artificial urinary sphincter, those with moderate post-prostatectomy incontinence (pad weight 100 to 400 gm/24 hours) were recommended to receive an artificial urinary sphincter or a male sling and those with mild post-prostatectomy incontinence (pad weight less than 100 gm/24 hours) were recommended to receive a male sling. RESULTS A total of 84 male sling (63%) and 49 artificial urinary sphincter (37%) procedures were performed. The surgeon recommendation was an artificial urinary sphincter in 63 men (47%) and a male sling in 46 (35%). A total of 24 men (18%) were given the option of either procedure. All patients recommended to receive a male sling chose it. When an artificial urinary sphincter was recommended, 75% of patients chose it, while 25% chose a male sling. When given a choice, 92% of patients chose a male sling and 8% chose an artificial urinary sphincter. CONCLUSIONS Most patients adhere to the surgeon recommendation. When men with post-prostatectomy incontinence are offered the choice of an artificial urinary sphincter vs a male sling, the opportunity to avoid using a mechanical device is preferable to undergoing a well established procedure. Men who strongly wish to avoid a mechanical device are willing to go against the surgeon recommendation for an artificial urinary sphincter.

Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies.

To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.