Rodney A. Appell

Female Stress Urinary Incontinence Clinical Guidelines Panel Summary Report on Surgical Management of Female Stress Urinary Incontinence

PURPOSE The American Urological Association convened the Female Stress Urinary Incontinence Clinical Guidelines Panel to analyze the literature regarding surgical procedures for treating stress urinary incontinence in the otherwise healthy female subject and to make practice recommendations based on the treatment outcomes data. MATERIALS AND METHODS The panel searched the MEDLINE data base for all articles through 1993 on surgical treatment of female stress urinary incontinence. Outcomes data were extracted from articles accepted after panel review. The data were then meta-analyzed to produce outcome estimates for alternative surgical procedures. RESULTS The data indicate that after 48 months retropubic suspensions and slings appear to be more efficacious than transvaginal suspensions, and also more efficacious than anterior repairs. The literature suggests higher complication rates when synthetic materials are used for slings. CONCLUSIONS The panel found sufficient acceptable long-term outcomes data (longer than 48 months) to conclude that surgical treatment of female stress urinary incontinence is effective, offering a long-term cure in a significant percentage of women. The evidence supports surgery as initial therapy and as a secondary form of therapy after failure of other treatments for stress urinary incontinence. Retropubic suspensions and slings are the most efficacious procedures for long-term success (based on cure/dry rates). However, in the panels opinion retropubic suspensions and sling procedures are associated with slightly higher complication rates, including longer convalescence and postoperative voiding dysfunction.

Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: A pooled analysis

OBJECTIVES To examine the safety, efficacy, and tolerability of tolterodine in four randomized, double-blind, parallel, multicenter, 12-week studies of patients with overactive bladder. METHODS Two of the four studies compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily) and placebo, one study compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily), and one study compared two dosages of tolterodine (1 and 2 mg twice daily) to placebo. Efficacy was determined from micturition diaries and patient perception of their bladder condition. Safety and tolerability were assessed from adverse events and laboratory measures. RESULTS A total of 1,120 patients were randomized and treated at 134 centers. For the primary efficacy variable, the number of micturitions/24 hours, pooled results showed a significant decrease from baseline for the 1 mg tolterodine (P < 0.001), 2 mg tolterodine (P < 0.001), and 5 mg oxybutynin (P < 0.01) groups, compared to placebo. Both tolterodine doses and oxybutynin significantly decreased incontinence episodes/24 hours and significantly increased volume voided/micturition, compared to placebo. Tolterodine at a dose of 2 mg twice daily and 5 mg oxybutynin twice daily were significantly more effective in improving patient perception of bladder condition than placebo. Tolterodine at a dose of 2 mg and 5 mg oxybutynin were equivalent in their effectiveness. Tolterodine at doses of 1 mg and 2 mg were tolerated significantly better than oxybutynin when adverse events, dry mouth (both frequency and intensity), dose reductions, and patient withdrawals were considered. CONCLUSIONS Although oxybutynin is highly effective, its clinical utility is limited by systemic side effects that lead to frequent discontinuation of treatment or dose reductions. Patients receiving tolterodine should not experience these limitations and instead will get safe and long-term effective treatment for their condition.

Prospective, Randomized, Double-Blind Study of the Efficacy and Tolerability of the Extended-Release Formulations of Oxybutynin and Tolterodine for Overactive Bladder: Results of the OPERA Trial

OBJECTIVE To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder. PATIENTS AND METHODS The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated. RESULTS Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events. CONCLUSIONS Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.

Prospective Randomized Controlled Trial of Extended-Release Oxybutynin Chloride and Tolterodine Tartrate in the Treatment of Overactive Bladder: Results of the OBJECT Study

OBJECTIVE To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder.

Abstract: This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks’ treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance.

Update of AUA Guideline on the Surgical Management of Female Stress Urinary Incontinence

PURPOSE We updated the 1997 American Urological Association guideline on female stress incontinence. MATERIALS AND METHODS MEDLINE searches of English language publications from 1994 and new searches of the literature published between December 2002 and June 2005 were performed using identified MeSH terms. Articles were selected for the index patient defined as the otherwise healthy woman who elected to undergo surgery to correct stress urinary incontinence or the otherwise healthy woman with incontinence and prolapse who elected to undergo treatment for both conditions. RESULTS A total of 436 articles were identified as suitable for inclusion in the meta-analysis, and an additional 155 articles were suitable for complications data only due to insufficient followup of efficacy outcomes in the latter reports. Surgical efficacy was defined using outcomes pre-specified in the primary evidence articles. Urgency (resolution and de novo) was included as an efficacy outcome due to its significant impact on quality of life. The primary efficacy outcome was resolution of stress incontinence measured as completely dry (cured/dry) or improved (cured/improved). Complications were analyzed similarly to the efficacy outcomes. Subjective complications (pain, sexual dysfunction and voiding dysfunction) were also included as a separate category. CONCLUSIONS The surgical management of stress urinary incontinence with or without combined prolapse treatment continues to evolve. New technologies have emerged which have impacted surgical treatment algorithms. Cystoscopy has been added as a standard component of the procedure during surgical implantation of slings.

Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence

Objective To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth. Methods Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose. Results Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P = .36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P = .85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P = .09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P = .007) or any dry mouth (P = .003) compared with those taking immediate-release oxybutynin. Conclusion At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group.

Extracorporeal magnetic innervation therapy for stress urinary incontinence.

OBJECTIVES To report the first data from a prospective clinical study to determine the feasibility of using extracorporeal magnetic innervation (ExMI) for the treatment of stress urinary incontinence. METHODS We studied 83 women with demonstrable stress urinary incontinence. Treatments were for 20 minutes, twice a week for 6 weeks. For treatment, the patient sits fully clothed on a special chair; within the seat is a magnetic field generator that produces the rapidly changing magnetic field flux. Objective measures included bladder diaries, dynamic pad weight testing, urodynamic studies, and quality of life survey. RESULTS Fifty patients have been followed up for longer than 3 months (33 patients for less than 3 months); 17 patients (34%) were dry, 16 (32%) were using not more than 1 pad per day, and 17 (34%) were using more than 1 pad per day. Pad use was reduced from 2.5 to 1.3 (P = 0.001) and leak episodes per day were reduced from 3.3 to 1.7 (P = 0.001). The pad weight was reduced from 20 to 15 g. Detrusor instability was found in 5 patients before but was demonstrated in only 1 patient after treatment. CONCLUSIONS ExMI therapy offers a new effective modality for pelvic floor muscle stimulation. ExMI is painless, there is no need for a probe, and no need to undress for treatments. Longer follow-up is required to determine how long the benefits of treatment last and whether retreatment will be necessary.

COLLAGEN INJECTION THERAPY FOR POST-PROSTATECTOMY INCONTINENCE

PURPOSE Post-prostatectomy incontinence has an incidence of 5 to 12% and greatly affects quality of life. Since the approval of glutaraldehyde cross-linked collagen there is a renewed interest in injectable urethral bulking agents. We investigated the long-term efficacy and prognostic criteria for transurethral collagen injection therapy for men with post-prostatectomy incontinence. MATERIALS AND METHODS From November 1993 to May 1995, 62 men with post-prostatectomy incontinence (54 after radical prostatectomy and 8 after transurethral resection of the prostate) were treated with collagen via a transurethral approach. Median followup was 29.0 months from the date of the last injection procedure. RESULTS Social continence was defined as dry or minimal leakage requiring at most 1 pad daily with activity. Of 62 patients 38.7% achieved social continence and 8.1% became totally dry. The success rate was 35.2 for radical prostatectomy versus 62.5% for transurethral prostatic resection patients. Of the patients who achieved social continence with at least 1-year followup 23 (60.9%) remained so with no further treatment. At 2-year followup 21 patients (42.8%) maintained social continence. The success rate was 27.3% for those who wore a penile clamp or condom catheter before treatment (3 of 11 patients), and only 21.4% for those who underwent transurethral incision of a bladder neck contracture (3 of 14). A median of 4 injection procedures and 20.0 ml. collagen were required to achieve social continence. CONCLUSIONS Transurethral collagen injection therapy is a reasonable treatment option for post-prostatectomy incontinence in select patients in whom more conservative therapy has failed. However, patients who have required a penile clamp, experienced continuous leakage or undergone transurethral incision of a bladder neck contracture are unlikely to respond well to this treatment.

Injectable agents in the treatment of stress urinary incontinence in women: where are we now?

Periurethral bulking agents have been used for decades. The only currently available agents (in the United States) include glutaraldehyde cross-linked collagen, autologous fat, and carbon bead technology. Initial subjective cure rates with collagen are acceptable, but with the majority of women requiring reinjection. The risk of allergic phenomena complicates collagen use. Autologous fat injection is initially effective in >50% of women, but resorption and fibrous replacement hamper the stability of the transplanted graft. Polytetrafluoroethylene and silicone are not currently approved by the US Food and Drug Administration because of particle migration. Materials in development include biologic agents such as allogeneic human collagen and autologous cartilage. Developmental synthetic agents include microballoon technology, hyaluronic acid with or without microsphere technology, hydroxylapatite, and a variety of polymeric technologies. Patient selection and material characteristics influence the optimal choice for injectable agent.