INTRODUCTION

Mixed urinary incontinence is the complaint of involuntary leakage associated with urgency and also with physical exertion, effort, sneezing, or coughing.¹ The prevalence varies widely in the literature. About one-third of women suffering from urinary incontinence (UI) have mixed urinary incontinence (MUI) with symptoms of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI).² Prevalence of MUI increases with age. In terms of evidence and lack thereof, many studies include patients with MUI, but it is rare for these studies to provide a separate analysis of patients with MUI.³

The assessment of MUI includes a thorough history of the patient’s urinary symptoms, bladder diaries, urinalysis, and measurement of a post-void residual volume.³ The role of urodynamics in MUI is unclear but establishing relative degrees of SUI and UUI may help in counseling patients about the most appropriate treatment option.³ It is conventional to try and categorize MUI as either stress or urgency predominant.

In this chapter we will address the challenge of how to approach management of mixed urinary incontinence in cooperation with the patient. It is important to realize that one single treatment may not cure MUI. Most therapies for MUI are not as effective when compared to the same treatments for pure SUI or UUI. It may be necessary to treat both components to be optimally effective, with the inherent risk of generating more adverse effects. This risk emphasizes the importance of thorough counseling of pros and cons to reach a satisfactory outcome for the patient in a well-balanced shared decision process involving the patient.

HOW TO MANAGE/TREAT MUI?

Basic suggestions

It is important to rule out other pathologies, like hematuria, recurrent urinary tract infections (UTI), symptomatic pelvic organ prolapse (POP), prior radiotherapy, or surgery for UI, pelvic masses, or the suspicion of a fistula. These symptoms and pathologies may require a different approach and we will not discuss that in this chapter.

When the above has been excluded we try, together with the patient and from her medical history and voiding diary, to assess which symptoms are most dominant. Is it MUI with predominantly urgency incontinence or is the stress component more dominant? The use of quality of life instruments may prove useful here.

From a safety perspective it is advocated to start with a treatment, which is least invasive and preferably cost effective, but only after having started discussing the effects fluid intake, bowel function, medication the patient uses, co-morbidity, and weight loss if indicated, may have on MUI in general. Offer continence pads or other containment devices if needed and offer timed or prompted voiding in elderly/care-dependent people. In postmenopausal women the beneficial effects of topical estrogens can be discussed.

Treat the most bothersome symptom first

Before starting treatment, it is important to identify the most bothersome part of the MUI. Start with non-invasive conservative therapy and evaluate the results. If these are not satisfactory enough, then try to find out whether the most dominant part is not effectively treated or whether the non-dominant part of MUI is causing a less than optimal outcome. Then carefully select a next step (likely a more invasive step in the dominant part of MUI, or a conservative first step in the non-dominant part). The following section sets out the various options, which are summarized in the flow-chart (Figure 1).

Pelvic floor physiotherapy (PFPT) is important in all patients with MUI. Bladder training can be started in combination with pelvic floor muscle training and re-education. Initial assessment includes examination and assessment of the status of the pelvic floor musculature, which can be classified using the modified Oxford grading system as described by Laycock.⁴ PFPT is usually best supervised by a specialist pelvic floor physiotherapist with a specific question; e.g., to re-educate an overactive or un underactive pelvic floor in combination with the patient’s history and bladder diary data. Re-evaluation of symptoms is suggested after, e.g., 3 months. With mild bothersome symptoms cure can be achieved, in the case of moderate to severe bother, improvement will likely be the best possible result.

Drug therapy

Depending on the severity of symptoms and the predominance of either the urgency or the stress component, one could add medication. Anti-cholinergics or beta-3-agonist are a first choice in urgency predominant incontinence, and these can be used in combination as they are synergistic in their actions. These drugs effectively diminish the urgency component, when compared to placebo, but the absolute size of the effect is small (NNT 6–12).⁵ The studies into the effect of these drugs suggest that the interval needed to assess any impact should be at least 4 weeks and in the case of positive effects can be continued for 6–9 months. There is a lack of data as to the long-term use of pharmacotherapy but commonly a trial to stop the medication is then an option, however if symptoms recur (which is often the case), the medication can be used longer term and potentially on an ad hoc basis. At the long term 34% of patients use antimuscarinics on an intermittent basis, which probably is related to adverse effects.⁶ One of the known issues with anticholinergic medication is cognitive dysfunction and caution is required particularly in older patients and if multiple anticholinergics are used.^7,8 If medication fails or has too many side effects an alternative drug could be chosen or a next step in the treatment may be considered. In the case patients may have had solitary PFPT OR medication in the past, sometimes a combination of the two is considered, that is PFPT/bladder training AND medication simultaneously. This combination therapy in general does not improve leaking, but does improve frequency and nocturia.⁵

In the case of predominant stress, one could consider Duloxetine, though the drug is not registered in every country for this purpose. Duloxetine improves SUI in about 50% of women; however, cure rates are low and it is not recommended first line.⁹ Furthermore, it may cause significant gastrointestinal and central nervous system adverse effects, leading to high rates of treatment discontinuation, therefore dose titration is advised.¹⁰ It also has a risk as with all drugs in this class of suicidal idealization.¹¹

If the aforementioned non-invasive measures are not effective enough, more invasive treatment modalities can be considered and discussed. At this point urodynamics may be of additional value to facilitate a clearer distinction of the dominant component of the mixed urinary incontinence.

MUS/colposuspension/fascial sling/bulking agents

In moderate or severe SUI PFPT probably causes some improvement. When this appears insufficient, a mid-urethral sling (MUS) could be the next option, in countries where mesh surgery for urinary incontinence is not paused. Counseling however is of utmost importance for this indication. Large cohorts (192 and 450 patients) show poorer results in patients with MUI compared to those with pure SUI (success rate 52–75% vs. 80–98%).^12,13 In a study of 1113 women treated with transobturator TVT (tension free vaginal tape), SUI was cured equally in stress- or urgency-predominant MUI. However, women with stress-predominant MUI had significantly better overall outcomes than women with urgency-predominant MUI.¹⁴ In contrast to studies examining older surgical methods, more recent studies have reported that UUI symptoms may improve in 30–85% of women with MUI after MUS surgery, which is an important topic to be discussed with the patient.^15,16

Non-mesh alternatives include abdominal colposuspension or fascial sling. Patients should be made aware that the urgency component could get worse after these more invasive treatments. A comparison of two parallel cohorts of patients undergoing Burch colposuspension for SUI, with and without detrusor overactivity (DO), found inferior outcomes in women with MUI.¹⁷

Urethral bulking agents are an option if a woman requests a low-risk procedure with the understanding that efficacy is lower compared to other surgical procedures, repeat injections are likely, and long-term durability and safety are not established (Cave: research only done in SUI patients, not MUI patients).^18,19,20 Whilst the risk of worsening urgency symptoms is less with these agents, the chance of improvement is also limited, suggesting bulking is more neutral on any process associated with OAB.²¹

Percutaneous tibial nerve stimulation

In the case PFPT and medication fail in patients suffering of MUI with predominant urgency, one could consider and discuss percutaneous tibial nerve stimulation (PTNS). PTNS delivers electrical stimuli to the sacral micturition center via the S2–S4 sacral plexus. Stimulation is percutaneous with a fine (34-G) needle, inserted just above the medial aspect of the ankle (P-PTNS). Transcutaneous stimulation is also available (T-PTNS) that delivers stimulation via surface electrodes that do not penetrate the skin.²² A systematic review shows Transcutaneous-PTNS to be effective in reducing OAB symptoms compared to sham treatment.²³ PTNS treatment cycles typically consist of 12 weekly treatments of 30 minutes. So, evaluation should not be too soon (after 8–12 weeks), since it takes some time to acquire effect. After the first 12 weeks, the interval should be stretched to one time in 2 weeks, one time in 3 weeks etc. A maintenance program of P-PTNS has been shown to be effective for up to 3 years.²⁴ Counsel patients well, since PTNS will not cure, but only improve. A recent study compared a sequential combined approach of TOT followed by PTNS in patients with MUI and a prevalent SUI component. Sixty patients after TOT were compared to 52 with TOT and sequential PTNS; the latter appeared to be more effective than TOT alone.²⁵ Newer modalities including implantable electrodes may become available in the next few years.

Onabotulinum toxin A

In the case of predominant urgency urinary incontinence when pharmacotherapy has failed or been declined then the more invasive step of intravesical bladder wall injections with 100 U Onabotulinum toxin A can be considered. One review demonstrated that Onabotulinum toxin A is an effective treatment for UUI (improvement and often cure), although not many studies on MUI have been published.²⁶ Drawbacks are that Onabotulinum toxin A injections have a risk of increased post-void residual (PVR) volume that needs clean intermitted catheterization (CIC) (5%) and an increased risk of UTIs/bacteriuria although the clinical significance of this remains uncertain (33%).²⁷

Where Onabotulinum toxin A is considered in patients who have had a MUS for the stress component, or in case after Onabotulinum toxin A for MUI a MUS is considered, patients have to be counseled that the odds of post-void residuals that need CIC are considerably greater than without Onabotulinum toxin A. A comparative study of 53 patients who received Onabotulinum toxin A for OAB to 49 who were given Onabotulinum toxin A after MUS, showed significantly more post-void residuals (8/53 vs. 13/49, respectively).²⁸

Two studies on a simultaneous treatment of both components of MUI are worth mentioning here. A randomized clinical trial comparing MUS and Onabotulinum toxin A versus MUS and placebo: short-term follow-up (3 months) showed no significant difference in incontinence episodes, although the group that received Onabotulinum toxin A demonstrated less urgency severity and frequency compared to placebo.²⁹ One study on a cohort of 55 patients with Onabotulinum toxin A and bulking agents showed a 40–50% chance on improvement of MUI, but with the inherent risk of urinary tract infections (13%) and post-void residuals that needed continuous intermittent catheterization in 33%.³⁰ Theoretically continuous catheterization can compromise the success of bulking as the agent may mold around the catheter.

Sacral nerve stimulation 

Another option is sacral nerve stimulation (SNS) if urgency urinary incontinence is the dominant aspect of MUI. It involves placing electrodes delivering low-amplitude stimulation to the sacral nerve roots, resulting in modulation of neural activity and stabilization of bladder electrical activity through a mechanism that is, as yet, not fully understood. A 2018 review of studies including SNS with >6 months follow-up reported dry rates of 43–56% and success rates 61–90%.³¹ Costs of SNS are high; compared to 200 U Onabotulinum toxin A, the 5 years, costs-effective analysis favors Onabotulinum toxin A.³² Furthermore, a common adverse event (AE) is pain at the implant site (range between 15% and 42%). Surgical revision rates range between 9% and 33%, and the most common reason for this was pain at the site of implantation.³¹

Bladder augmentation/cystoplasty/urinary diversion

Although historically urologists might have offered an augmentation cystoplasty or urinary diversion, their role is becoming more limited as the newer procedures have replaced them and there is limited evidence of the effectiveness of these procedures, specifically for the treatment of idiopathic OAB.³³ Furthermore, augmentation cystoplasty and urinary diversion are associated with high risks of short- and long-term complications. The need to perform CIC following augmentation cystoplasty is common and life-long surveillance is necessary. If a urinary diversion is considered in patients who failed previous less-invasive therapies for the treatment of the UUI-part of MUI, patients have to be thoroughly counseled and should be willing to accept a stoma, and be warned about the potential risk of malignancy. These procedures in our opinion, are thus better to avoid in MUI.

Shared decision making 

Treating MUI is a challenge, since results are often less promising as compared to, e.g., SUI. An aid in the decision process is the flow diagram shown in Figure 1. Since results are not easily predicted in the treatment of MUI, the authors of this chapter strongly encourage counseling the patient of the pros and cons in a shared decision manner together with the patient! Listen carefully to the patient and find out what her expectations are.

MUI is a quality-of-life issue and risks versus benefits of any treatment should be weighed carefully. It is important to determine reasonable therapeutic goals for symptom control before starting therapy. Patients should realize that acceptable symptom control may involve trial and error of the various lines of therapy and is usually a long-term process requiring adjustments to treatment plans and ongoing re-evaluation of treatments.³⁴

Involvement in shared decision making (SDM) is also strongly encouraged to improve patient satisfaction, and that is what both patients and their caregivers are striving at. In other areas of medicine, it has been shown that the more patients were involved in shared decision making, the more they proved to be satisfied with their healthcare.³⁵ Long-term follow up ideally with regular review using validated instruments will allow future comparison of outcomes for planning management strategies.³⁶

PRACTICE RECOMMENDATIONS