Pharmacologic Treatment in Postprostatectomy Stress Urinary Incontinence

doi:10.1016/j.eururo.2006.08.005

European Urology

Volume 51, Issue 6, June 2007, Pages 1559-1564

https://doi.org/10.1016/j.eururo.2006.08.005 Get rights and content

Abstract

Objectives

The aim of this study was to assess efficacy and safety of association of duloxetine and rehabilitation compared with rehabilitation alone in men with SUI after radical retropubic prostatectomy (RRP), and to compare continence rate even after planned duloxetine suspension.

Methods

After catheter removal, 112 patients were randomized to receive rehabilitation and duloxetine (group A) or rehabilitation alone (group B), for 16 wk. Inclusion criteria: postprostatectomy SUI with daily incontinent episodes frequency (IEF) of four or greater.

After 16 wk both groups suspended duloxetine/placebo and continued rehabilitation. All patients completed incontinence quality of life (I-QoL) questionnaire and bladder diary. Wilcoxon test was used to analyse changes in IEF and in I-QoL score; Fisher exact test was used to compare continent patients between the groups.

Results

Adverse events for duloxetine was 15.2%. 102 men completed the study. There was a significant decrease in pad use in group A. After 16 wk, 39 patients versus 27 were dry (p = 0.007). At 20 wk, 4 wk after planned interruption of duloxetine, we observed a U-turn, 23 patients were completely dry in group A versus 38 in group B (p = 0.008). Whereas, after 24 wk, 31 in group A versus 41 in group B were dry (p = 0.08). The decrease in IEF and improvements in I-QoL scores were significantly greater in group A for the first 16 wk.

Conclusions

The data suggest that combination therapy might provide another treatment option for SUI in men that might increase the percentage of early postsurgery continence.

Introduction

Stress urinary incontinence (SUI) is the complaint of involuntary loss of urine on effort or exertion, or on sneezing, coughing or laughing [1]. Urinary incontinence remains a serious sequela after radical prostatectomy, despite better understanding of pelvic anatomy and improvement in surgical technique [2]. The recommended first-line treatment for men with postprostatectomy urinary incontinence is pelvic floor muscle training (PFMT) [3].

Duloxetine, a potent serotonine/norepinephrine reuptake inhibitor has been evaluated in a clinical trial program of one phase 2 and three phase 3 placebo-controlled trials worldwide, that involved 1913 patients, and proved an effective and safe treatment on women with SUI [4], [5], [6], [7]. Currently there is no pharmacologic treatment approved for stress urinary incontinence in men.

PFMT decreases the frequency of incontinence episodes and reduces the amount of leakage by compressing the urethra during activity [8]. While duloxetine plays a key role in normal urethral sphincter closure, it is supposed to increase rhabdosphincter tone and contraction by stimulating the Onuf nucleus [9], [10]. Pelvic floor muscle and rhabdosphincter are not supported by the same nerves, and pelvic floor exercises do not activate the urethral sphincter [11]. A recent study demonstrated how early PFMT can halve incontinence time and reduce the degree of leakage in men after radical retropubic prostatectomy (RRP) [12]. A previous study conducted on women indicates that PFMT and duloxetine could have cumulative positive effects on SUI [11].

These preliminary observations supported the hypothesis that duloxetine and PFMT could have an additional effect even on male postprostatectomy SUI if sphincter innervation is undamaged. Furthermore, unlike women with SUI, the majority of male patients recover urinary control 1 yr after surgery because of the natural recovery of the sphincter function, so everything points to the fact that duloxetine in male incontinence could be employed only soon after surgery and for a limited time.

The primary objectives of this study was to assess duloxetine’s efficacy and safety in men with SUI after RRP, to evaluate the effect of association of duloxetine and PFMT, to compare the effectiveness of combined treatment versus PFMT alone, and to evaluate whether duloxetine may have a role in early first-line approach for postprostatectomy incontinence. The secondary objective was to compare the long-term continence rate outcome even after planned duloxetine suspension.

Section snippets

Methods

This prospective, randomized, single-blind, autonomous study was conducted between January 2005 and April 2006. One hundred fifty-three patients who had undergone standard RRP were considered for this protocol. Ten days after catheter removal (average: 8.8 d after surgery; range: 7–14), 112 of 153 RRP patients were randomized to receive PFMT and 40 mg duloxetine twice daily (group A or combined treatment), or PFMT and placebo (group B or PFMT only), for 16 wk (Table 1). A single-blinded

Results

A total of 112 men were randomized for treatment with PFMT alone or in combination with duloxetine. Ten (11.2%) of these patients were removed from the study prematurely for adverse events, 9 (15.2%) for duloxetine and 1 (1.8%) for placebo (p = 0.01), with nausea being the most common reason for discontinuation (70%). Overall, 102 men completed the 24-wk study, 50 in group A and 52 in group B. There were no significant differences between demographic, clinical, surgical, and incontinence

Discussion

Urinary continence is the result of a correct bladder storage and emptying. This mechanism is under the control of the peripheral and central nervous systems. In particular, urethral closure comes from innervations of the pudendal nerve, which determines a good functioning of the urethral rhabdosphincter. The activity of the pudendal nerve is increased by serotoninergic and noradrenergic neurotransmitters in the sacral Onuf nucleus. Duloxetine enhances the concentration of both these amines by

Conclusions

Duloxetine showed a facilitative effect on early continence recovery, while avoiding negative psychological impact on oncologic patients. Moreover, duloxetine was shown to be complementary to PFMT with a synergic clinical effect demonstrated by a significant reduction of incontinence episodes in postprostatectomy incontinence, compared with PFMT alone. The data suggest that combination therapy might provide another treatment option for SUI in men that might increase the percentage of early

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Cited by (79)

Use of Duloxetine for Postprostatectomy Stress Urinary Incontinence: A Systematic Review
2021, European Urology Focus
Citation Excerpt :
All studies evaluated patients with SUI following radical prostatectomy for prostate cancer, but two studies also included a small proportion of patients who had undergone pelvic radiotherapy, TURP, and radical cystectomy and orthotopic ileal neobladder reconstruction [21,22]. Duloxetine was commenced early (following catheter removal after radical prostatectomy) in two studies, which assessed whether there was any additional benefit of duloxetine treatment in combination with PFMT, compared with PFMT alone, in recovery of early continence [18,19]. The remainder of the studies assessed duloxetine as a treatment for PPI after failure of PFMT, starting at least 6–12 mo after surgery.
The recommended treatment of postprostatectomy stress urinary incontinence (PPSUI) after failure of pelvic floor muscle training is primarily surgical intervention with a male sling or artificial urinary sphincter. The use of pharmacological therapy in this setting is unlicensed and controversial.
To systematically review the available evidence regarding the efficacy and safety of duloxetine for the treatment of stress urinary incontinence following prostate surgery (radical or endoscopic).
The EMBASE, MEDLINE/PubMed, and Cochrane Central Register of Controlled Trials were searched from inception up until April 17, 2020. All studies evaluating the role of duloxetine in men with PPSUI were included. Two reviewers independently screened all articles, searched the reference lists of retrieved articles, and performed data extraction. The quality of evidence and risk of bias were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE); Cochrane; and Risk of Bias in Nonrandomised Studies of Interventions (ROBINS-I) tools.
The search yielded 234 studies. After excluding duplicates, 140 titles and abstracts were screened, and eight reports (348 patients) were eligible for inclusion in the final review. Duloxetine was assessed in two scenarios: (1) early use to reduce the time to attain continence and (2) treatment of persistent PPSUI. Most men had mild-to-moderate incontinence at baseline. Overall, duloxetine resulted in a mean dry rate of 58% (25–89%), mean improvement in pad number of 61% (12–100%), and mean improvement in 1-h pad weight of 68% (53–90%) at short-term follow-up (mean 1–9 mo; low to moderate certainty of evidence). However, mean adverse event rates were relatively high, and treatment was discontinued in 38% (low certainty of evidence).
Duloxetine has demonstrated good short-term cure and/or improvement in treating men with persistent PPSUI, as well as in reducing the time to attain continence. However, a proportion of men discontinue treatment due to adverse events. The overall certainty evidence is moderate to low, with heterogeneity between studies and methodological limitations. However, we have highlighted the need for further randomised trials with longer follow-up, utilising consistent outcome reporting measures. Despite these limitations, the findings from this review will aid patient counselling regarding this less invasive treatment option, thereby allowing personalisation of care centred around the values and preferences of individual patients.
Duloxetine has good success rates in the short term, in terms of improving incontinence symptoms in men who have undergone prostate surgery. However, some men experience side effects bad enough to require cessation of treatment. Further studies are needed to determine whether duloxetine maintains its effectiveness in the long term.
EAU Guidelines on Assessment and Nonsurgical Management of Urinary Incontinence [Figure presented]
2018, European Urology
The European Association of Urology guidelines on urinary incontinence (UI) have been updated in cyclical fashion with successive major chapters being revised each year. The sections on assessment, diagnosis, and nonsurgical treatment have been updated as of mid-2016.
We present a condensed version of the full guideline on assessment and nonsurgical management of UI, with the aim of improving accessibility and increasing their dissemination.
Our literature search was updated from the previous cut-off of July 2010 up to April 2016. Evidence synthesis was carried out by a pragmatic review of current systematic reviews and any newer subsequent high-quality studies, based on Population, Interevention, Comparator, and Outcome questions. Appraisal was conducted by an international panel of experts, working on a strictly nonprofit and voluntary basis, to develop concise evidence statements and action-based recommendations using modified Oxford and GRADE criteria.
The guidelines include algorithms that summarise the suggested pathway for standard, uncomplicated patients with UI and are more useable in daily practice. The full version of the guideline is available at http://uroweb.org/guideline/urinary-incontinence/.
These updated guidelines provide an evidence-based summary of the assessment and nonsurgical management of UI, together with a clear clinical algorithm and action-based recommendations. Although these guidelines are applicable to a standard patient, it must be remembered that therapy should always be tailored to individual patients’ needs and circumstances.
Urinary incontinence is a very common condition which negatively impacts patient's quality of life. Several types of incontinence exist and since the treatments will vary, it is important that the diagnostic evaluation establishes which type is present. The diagnosis should also identify patients who need rapid referral to an appropriate specialist. These guidelines aim to provide sensible and practical evidence-based guidance on the clinical problem of urinary incontinence.
Pelvic floor muscle exercise with or without duloxetine for postprostatectomy urinary incontinence: A retrospective single-center study
2023, Medicine (United States)
Management of functional outcomes after radical prostatectomy in the Nordic countries: A survey of uro-oncological centers
2023, Research Square
Current and Emerging Pharmacological Targets and Treatments of Urinary Incontinence and Related Disorders
2023, Pharmacological Reviews
Latest Evidence on Post-Prostatectomy Urinary Incontinence
2023, Journal of Clinical Medicine

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Prostate CancerPharmacologic Treatment in Postprostatectomy Stress Urinary Incontinence

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Am J Obstet Gynecol

J Urol

J Urol

Eur Urol

J Urol

Eur Urol

Eur Urol

Lancet

Eur Urol

Eur Urol

Prostate Cancer
Pharmacologic Treatment in Postprostatectomy Stress Urinary Incontinence