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BackgroundIdentifying men whose lower urinary tract symptoms (LUTS) may benefit from surgery is challenging.ObjectiveTo identify routine diagnostic and urodynamic measures associated with treatment decision-making, and outcome, in exploratory analyses of the UPSTREAM trial.Design, setting, and participantsA randomised controlled trial was conducted including 820 men, considering surgery for LUTS, across 26 hospitals in England (ISCTRN56164274).InterventionMen were randomised to a routine care (RC) diagnostic pathway (n = 393) or a pathway that included urodynamics (UDS) in addition to RC (n = 427).Outcome measurements and statistical analysisMen underwent uroflowmetry and completed symptom questionnaires, at baseline and 18 mo after randomisation. Regression models identified baseline clinical and symptom measures that predicted recommendation for surgery and/or surgical outcome (measured by the International Prostate Symptom Score [IPSS]). We explored the association between UDS and surgical outcome in subgroups defined by routine measures.Results and limitationsThe recommendation for surgery could be predicted successfully in the RC and UDS groups (area under the receiver operating characteristic curve 0.78), with maximum flow rate (Qmax) and age predictors in both groups. Surgery was more beneficial in those with higher symptom scores (eg, IPSS >16), age 47.6, and bladder contractility index >123.0. In the UDS group, urodynamic measures were more strongly predictive of surgical outcome for those with Qmax >15, although patient-reported outcomes were also more predictive in this subgroup.ConclusionsTreatment decisions were informed with UDS, when available, but without evidence of change in the decisions reached. Despite the small group sizes, exploratory analyses suggest that selective use of UDS could detect obstructive pathology, missed by routine measures, in certain subgroups.Patient summaryBaseline clinical and symptom measurements were able to predict treatment decisions. The addition of urodynamic test results, while useful, did not generally lead to better surgical decisions and outcomes over routine tests alone.

AIM: The aim of this study is to evaluate safety and efficacy of ASP8302, a novel positive allosteric modulator for the muscarinic M3 receptor (M3-PAM), in patients with underactive bladder (UAB).METHODS: A randomized, double-blind, placebo-controlled multicenter study was performed in adult male/female subjects with UAB, defined as incomplete bladder emptying (postvoid residual volume [PVR] > 100 ml) without significant bladder outlet obstruction and/or overactive bladder. Subjects were randomized (1:1) to receive 4-week oral once-daily administration of 100 mg ASP8302 or matching placebo. Primary endpoint was a change from baseline in PVR measured by catheterization after standardized bladder filling (PVRC2 ). Other endpoints included PVR and bladder voiding efficiency (BVE) measured in various ways, uroflowmetry, bladder diary, and questionnaires. Pressure-flow studies were performed in a subgroup.RESULTS: One hundred and thirty-five patients were randomized (ASP8302 group: 65 patients, placebo group: 70 patients). The median change in PVRC2 was -40.0 ml (ASP8302) versus -35.0 ml (placebo) and the difference between groups was -5.0 ml (p = 0.960). In males, functional and symptomatic outcomes improved, for example, maximum urine flow rate (Qmax ) and detrusor pressure at Qmax (Pdet.Qmax ) increased (mean difference in change ASP8302 vs. placebo: 3.8 ml/s, p = 0.031 and 12.7 cm H2 O, p = 0.034, respectively). Urinary incontinence episodes/24 h decreased in males with preexisting incontinence (mean difference: -0.35; p = 0.028). The incidence of adverse events was similar between study groups (ASP8302: 33.3%, placebo: 31.4%). In the included subjects, both baseline urine flow and bladder voiding pressure was low. Compared with PVR, simultaneous BVE measurements were more consistent between various methods (spontaneous vs. standardized bladder filling, catheterization vs. ultrasound [US]).CONCLUSIONS: ASP8302 was safe and well tolerated in patients with UAB identified by nonurodynamic clinical criteria, but it did not show efficacy in the primary endpoint. However, in males it showed improvement of symptoms and functional parameters. BVE (using US) is a more optimal outcome measure than PVR in UAB.

BackgroundCompletion rates and correspondence to other measures need to be established for the International Consultation on Incontinence Questionnaire (ICIQ) bladder diary (ICIQ-BD) in the assessment of male lower urinary tract symptoms (LUTS).ObjectiveTo evaluate ICIQ-BD completion rates, frequency, volume, and sensation reporting for men.Design, setting, and participantsBaseline data from the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM) randomised controlled trial evaluating 820 men at 26 UK hospitals, looking at the ICIQ-BD, uroflowmetry, International Prostate Symptom Score, and ICIQ symptom score for male LUTS (ICIQ-MLUTS), were assessed.Outcome measurements and statistical analysisThe ICIQ-BD, IPSS, ICIQ-MLUTS, and uroflowmetry data at baseline obtained from UPSTREAM were assessed. Correlations were analysed by Pearson’s correlation coefficient, and comparison between groups were performed using paired or unpaired t tests or Tukey’s test. All statistical tests were two sided and the strength of evidence was presented using p values.Results and limitationsOf the participants, 25.0% (205/820) provided complete voiding and bedtime information for 3 d, 41.2% (338/820) omitted bedtime information, and the remainder omitted some or all voiding information. Median values (minimum – maximum) of 24-h, daytime, and night-time frequencies were 9.7 (3.3–24.0), 7.7 (3.3–22.7), and 1.7 (0.0–5.7), respectively. The mean voided volume per micturition for day and night times were 175.8 ± 74.2 and 264.4 ± 150.7 ml (p < 0.001), respectively. For fully completed diaries, day- and night-time frequency showed a weak-to-moderate correlation with symptom score questionnaires. More severe nocturia was generally reported in symptom scores than in the ICIQ-BD. In patients with high bother for increased daytime frequency (symptom), the mean daytime frequency (ICIQ-BD) was 9.6 ± 3.2 versus 7.6 ± 2.2 for low bother (p < 0.001). High bother for nocturia showed night-time frequency of 2.3 ± 1.2 versus 1.5 ± 1.1 for low bother (p < 0.001). For fully and partially completed diaries, ICIQ-BD sensation scores correlated weakly with symptom scores. Voided volumes from the bladder diary and uroflowmetry correlated weakly.ConclusionsTwo-thirds of men (543/820) fully completed voiding information in the ICIQ-BD, but many omitted bedtime information, limiting the ability to quantify nocturia and diagnose nocturnal polyuria.Patient summaryMost men with urinary symptoms complete a bladder diary fully but may fail to indicate bedtimes. Extra information from a diary helps support symptom questionnaires to explain a patient’s urinary habits.

Objectives: To develop and test the psychometric properties of a concise, patient-reported questionnaire, designed to assess key aspects of the radical cystectomy (RC) patient pathway that are important to both patients and clinicians. Patients and Methods: Draft items were developed by a consultation with a 13-member expert clinical panel, and the in-depth qualitative analysis of 14 semi-structured interviews with patients who had received RC within the previous 18months. A further nine cognitive interviews with patients refined the items and ensured they were easy to complete. Pilot testing in 122 patients recruited from five hospitals in England tested the properties of validity and reliability of the resulting 17-item questionnaire. Results: Patients and clinicians identified the following aspects as important for the delivery of quality patient care. These included timely referral and initial test results; an explanation of risk/benefits of treatment; access to a cancer nurse specialist; training and support in stoma management; timely surgery, surgical complications, and timely follow-up. Pilot testing showed missing data was low (≤3% for all items), and between 73% and 89% of the responses to items were the most positive about their care (indicating ceiling effects). Five items were identified using factor analysis as being statistically related (Cronbach’s α 0.76, intraclass correlation coefficient test–retest reliability of 0.95) and formed the scored part of the tool ‘care and support’, scored 0–16. There was insufficient evidence at this stage to show the tool was capable of measuring differences between cancer centres. Conclusion: We have developed a questionnaire that captures aspects of quality of care within the RC patient pathway. The results support the validity and reliability of the 17-item Cystectomy-Pathway Assessment Tool (C-PAT). We envisage the tool can be the basis for audit of the patient reported assessment of the quality of care for individual cancer centres.

Background Stress urinary incontinence is common in men after prostate surgery and can be difficult to improve. Implantation of an artificial urinary sphincter is the most common surgical procedure for persistent stress urinary incontinence, but it requires specialist surgical skills, and revisions may be necessary. In addition, the sphincter is relatively expensive and its operation requires adequate patient dexterity. New surgical approaches include the male synthetic sling, which is emerging as a possible alternative. However, robust comparable data, derived from randomised controlled trials, on the relative safety and efficacy of the male synthetic sling and the artificial urinary sphincter are lacking. Objective We aimed to compare the clinical effectiveness and cost-effectiveness of the male synthetic sling with those of the artificial urinary sphincter surgery in men with persistent stress urinary incontinence after prostate surgery. Design This was a multicentre, non-inferiority randomised controlled trial, with a parallel non-randomised cohort and embedded qualitative component. Randomised controlled trial allocation was carried out by remote web-based randomisation (1 : 1), minimised on previous prostate surgery (radical prostatectomy or transurethral resection of the prostate), radiotherapy (or not, in relation to prostate surgery) and centre. Surgeons and participants were not blind to the treatment received. Non-randomised cohort allocation was participant and/or surgeon preference. Setting The trial was set in 28 UK urological centres in the NHS. Participants Participants were men with urodynamic stress incontinence after prostate surgery for whom surgery was deemed appropriate. Exclusion criteria included previous sling or artificial urinary sphincter surgery, unresolved bladder neck contracture or urethral stricture after prostate surgery, and an inability to give informed consent or complete trial documentation. Interventions We compared male synthetic sling with artificial urinary sphincter. Main outcome measures The clinical primary outcome measure was men’s reports of continence (assessed from questions 3 and 4 of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form) at 12 months post randomisation (with a non-inferiority margin of 15%). The primary economic outcome was cost-effectiveness (assessed as the incremental cost per quality-adjusted life-year at 24 months post randomisation). Results In total, 380 men were included in the randomised controlled trial (n = 190 in each group), and 99 out of 100 men were included in the non-randomised cohort. In terms of continence, the male sling was non-inferior to the artificial urinary sphincter (intention-to-treat estimated absolute risk difference –0.034, 95% confidence interval –0.117 to 0.048; non-inferiority p = 0.003), indicating a lower success rate in those randomised to receive a sling, but with a confidence interval excluding the non-inferiority margin of –15%. In both groups, treatment resulted in a reduction in incontinence symptoms (as measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form). Between baseline and 12 months’ follow-up, the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form score fell from 16.1 to 8.7 in the male sling group and from 16.4 to 7.5 in the artificial urinary sphincter group (mean difference for the time point at 12 months 1.30, 95% confidence interval 0.11 to 2.49; p = 0.032). The number of serious adverse events was small (male sling group, n = 8; artificial urinary sphincter group, n = 15; one man in the artificial urinary sphincter group experienced three serious adverse events). Quality-of-life scores improved and satisfaction was high in both groups. Secondary outcomes that showed statistically significant differences favoured the artificial urinary sphincter over the male sling. Outcomes of the non-randomised cohort were similar. The male sling cost less than the artificial sphincter but was associated with a smaller quality-adjusted life-year gain. The incremental cost-effectiveness ratio for male slings compared with an artificial urinary sphincter suggests that there is a cost saving of £425,870 for each quality-adjusted life-year lost. The probability that slings would be cost-effective at a £30,000 willingness-to-pay threshold for a quality-adjusted life-year was 99%. Limitations Follow-up beyond 24 months is not available. More specific surgical/device-related pain outcomes were not included. Conclusions Continence rates improved from baseline, with the male sling non-inferior to the artificial urinary sphincter. Symptoms and quality of life significantly improved in both groups. Men were generally satisfied with both procedures. Overall, secondary and post hoc analyses favoured the artificial urinary sphincter over the male sling. Future work Participant reports of any further surgery, satisfaction and quality of life at 5-year follow-up will inform longer-term outcomes. Administration of an additional pain questionnaire would provide further information on pain levels after both surgeries. Trial registration This trial is registered as ISRCTN49212975. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 36. See the NIHR Journals Library website for further project information.

Overactive bladder (OAB) negatively affects work productivity and quality of life in sufferers. Its overall impact is likely to increase as a result of increasing prevalence in an ageing population. The pathophysiology of OAB is not completely understood but the β3-adrenoceptor, which is highly expressed in the urinary bladder, is thought to be important for mediating human detrusor relaxation during the storage phase. Clinical trial results have demonstrated that mirabegron, a selective β3-adrenoceptor agonist offers substantial clinical efficacy and good adherence rates over 12 months. Furthermore, due to its different mechanism of action, it is likely to offer a favourable tolerability profile when compared with antimuscarinic agents, resulting in improved persistence over long-term treatment. Finally, from a health economic perspective, despite its higher drug acquisition cost, mirabegron has been found to be cost-effective, owing to the greater increase in quality-adjusted-life-years gained, when compared to antimuscarinic medications. The PubMed database was searched for English language articles published between 1 January 2005 to 31 January 2022, on the subject of mirabegron. Search terms included "mirabegron", "overactive bladder", "β3-adrenoceptor agonist", "urinary incontinence". This review summarises the evidence for mirabegron as a treatment option for the management of OAB.

We established severity banding ranges, bother assessment and key item content in principal patient reported outcomes measures in men seeking therapy for lower urinary tract symptoms.Data for International Prostate Symptom Score (I-PSS) and International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) were derived from a study evaluating 820 men at 26 United Kingdom hospitals. ROC curves were used to establish severity bandings.Classification tree showed that thresholds between mild-moderate and moderate-severe severity bands were 15 and 27 for I-PSS, 16 and 26 for ICIQ-MLUTS/severity, and 22 and 81 for ICIQ-MLUTS/bother, respectively. Highest area under the ROC curve and lowest Akaike's information criteria of univariate logistic regression indicated that ICIQ-MLUTS/bother was more related to global quality of life than were I-PSS and ICIQ-MLUTS/severity. The symptoms affecting I-PSS-quality of life (QoL) were only fully identified by ICIQ-MLUTS, because 2 key symptoms (urinary incontinence and post-micturition dribble) are not measured by I-PSS. ICIQ-MLUTS demonstrated that bother of some lower urinary tract symptoms is disproportionate to severity, and that persisting high bother levels following surgery are more likely due to storage (18% to 25%) and post-voiding (18% to 28%) lower urinary tract symptoms than voiding lower urinary tract symptoms (5% to 13%). Symptom improvement after surgery was uncertain if baseline I-PSS-QoL score was less than 3.The severity threshold scores were measured for the 2 key lower urinary tract symptoms patient reported outcomes measures, and the results indicate suitable categories of symptom severity for use in men referred for urological care. The ICIQ-MLUTS measures all the lower urinary tract symptoms affecting quality of life and includes individual symptom bother scores.

Aims To inform and guide patient-centred care for men with lower urinary tract symptoms (LUTS), by providing in-depth qualitative evidence regarding men's perspectives on treatment decision-making for LUTS. Methods An interview study of men recruited from 26 English urology departments. Purposive sampling captured surgical/nonsurgical treatment decisions, and diversity in demographics and symptom burden, in men who had urodynamics and those who did not. After diagnostic assessments, men were interviewed either pre-treatment or after LUTS surgery. Thematic analysis was conducted. Participants' descriptions of how LUTS treatment decisions were made were categorised as patient-led, doctor-led, or shared. Results A total of 41 men participated (25 pre-treatment, 16 post-surgery), ages 52-89. Twenty out of 41 described the treatment decision as shared with their consultant, 14 as doctor-led, and seven as patient-led. There was no obvious association between treatment decision-making style and patients' satisfaction with either clinicians' role in their decision or their treatment decision. Incomplete or rushed discussions and misperceptions of LUTS and its treatment were reported, indicating a risk of suboptimal decision-making support by clinicians. As well as clinician opinion, men's treatment decision-making was influenced by the results of urological assessments, comparing current symptoms with possible side-effects of surgery, and others' experiences and opinions. Conclusions Men with LUTS report and prefer different kinds of decision-making support from their clinicians, who must tailor their input to patients' preferences and needs. Patients' treatment decision-making involves multiple factors and can be challenging, and areas of inadequate clinician support were identified. Recommendations for patient-centred consultations about LUTS treatment are presented.

Objective To determine the cost-effectiveness of the current gold standard operation of transurethral resection of the prostate (TURP) compared to the new laser technique of thulium laser transurethral vaporesection of the prostate (ThuVARP) in men with benign prostatic obstruction (BPO) within the United Kingdom (UK) National Health Service (NHS). Patients and methods The trial was conducted across seven UK centres (four university teaching hospitals and three district general hospitals). 410 men aged 18 years and older presenting with either bothersome lower urinary tract symptoms (LUTS) or urinary retention secondary to BPO, and suitable for surgery, were randomised (whilst under anaesthetic) 1:1 to receive the TURP or ThuVARP procedure. Resource use in relation to the operation, initial inpatient stay, and subsequent use of NHS services was collected for 12 months from randomisation (equivalent to primary effectiveness outcome) using hospital records and patient questionnaires. Resources were valued using UK reference costs. QALYs (quality adjusted life years) were calculated from the EQ-5D-5L questionnaire completed at baseline, 3- and 12-months. Total adjusted mean costs, QALYs and incremental Net Monetary Benefit statistics were calculated: cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty. Results The total adjusted mean secondary care cost over the 12 months in the TURP arm (£4244) was £9 (95% CI of -£376 to £359) lower than the ThuVARP arm (£4253). The ThuVARP operation took on average 21 minutes longer than TURP. The adjusted mean difference of Quality Adjusted Life Years (QALYs) (0.01 favouring TURP, 95% CI of -0.01 to 0.04) was similar between the arms. There is a 76% probability that TURP is the cost-effective option compared with ThuVARP at the £20,000 per QALY willingness to pay threshold used by National Institute for Health and Care Excellence (NICE). Conclusion One of the anticipated benefits of the laser surgery, reduced length of hospital stay with an associated reduction in cost, did not materialise within the study. The longer duration of the ThuVARP procedure is important to consider, both from a patient perspective in terms of increased time under anaesthetic, and from a service delivery perspective. TURP remains a highly cost-effective treatment for men with BPO.

Objectives To characterise the clinical features and to discover predictive factors of adult males with nocturnal enuresis (NE). Patients and methods A total of 43 eligible adult male patients (mean age was 57.8 years) were recruited prospectively over a 2-year period. After documentation of medical history, lower urinary tract symptoms (LUTS) were assessed using the International Consultation on Incontinence Modular Questionnaire-male LUTS (ICIQ-MLUTS), and a 3-day ICIQ-bladder diary (ICIQ-BD). Video-urodynamic studies (VUDS) were conducted conforming to the International Continence Society standards. Univariate and multivariate linear regressions were performed to determine potential predictive factors. Results Patients with NE had a variety of LUTS and had a high incidence of obesity and comorbidities. On the ICIQ-BD, NE was associated with nocturnal polyuria (NP), reduced nocturnal bladder capacity (NBC), or a combination of both. Subgroup analysis indicated that patients with more frequent NE had: higher body mass index (BMI); more comorbidities; reduced daytime urinary frequency and urgency quality of life (QoL) sub-scores; and increased stress urinary incontinence (SUI) and nocturnal bedwetting sub-scores. Patients with reduced NBC only, had fewer NE episodes, while patients with NP, or with both NP and reduced NBC were more likely have frequent NE. Multivariate analysis confirmed that: BMI; neurogenic causes; sub-scores of SUI QoL and bedwetting domain; the presence of reduced NBC, and both NP and reduced NBC; and bladder outlet obstruction, were all independent predictive factors for the severity of NE. Conclusions NE n the adult male should be systemically assessed and treated, as obesity, neurogenic disorders, excessive urine production, bladder storage and emptying dysfunctions are risk factors. Bladder diaries and VUDS provide valuable information on potential pathophysiological causes, which could assist clinical evaluation and selection of focussed treatment.

AIM: The International Continence Society (ICS) has standardized quality control and interpretation of uroflowmetry and urodynamics. We evaluated traces from two large studies of male lower urinary tract symptoms (UPSTREAM and UNBLOCS) against ICS standards of urodynamic equipment and practice.METHODS: Ten percent of uroflowmetry and urodynamics traces were selected at random from hospital sites. A data capture template was designed from the ICS Fundamentals of Urodynamic Practice checklist. Two pretrained blinded assessors extracted the data, with a third assessor to arbitrate. Departmental records of calibration checks and equipment maintenance were scrutinized.RESULTS: Seven out of twenty-five (28%) departments reported no calibration checks. Four sites (16%) could not provide annual service records. In 32 out of 296 (10.8%) uroflowmetry traces, findings were affected by artifact. One hundred ten urodynamic study traces were reviewed; in 11 records (10%), key pressure traces were incompletely displayed. In 30 (27.2%), reference zero was not set to atmospheric pressure. Resting pressures were outside the expected range for 36 (32.7%). Pressure drift was seen in 18 traces (16.4%). At pressure-flow study commencement, permission to void was omitted in 15 (13.6%). Cough testing after voiding was done in 71.2%, but the resulting cough spikes were significantly different in 16.5%. Erroneous diagnosis of bladder outlet obstruction (BOO) was identified in six cases (5.5%).CONCLUSIONS: Erroneous diagnosis of BOO is a serious error of interpretation, as it could lead to unnecessary surgery. Other errors of standardization, testing, and interpretation were identified with lower risk of adverse implications. Inconsistent documentation of service records mean equipment accuracy is uncertain.

AIMS: Mounting evidence from experimental animal and human studies suggests that cross-sensitization exists between different organs. Lower urinary tract (LUT) and bowel dysfunction commonly overlap, and the role of cross-sensitization between pelvic visceral organs is uncertain.METHODS: At the International Consultation on Incontinence Research Society (ICI-RS) meeting in 2018, a panel of clinicians participated in a discussion on bladder and bowel interactions in the context of pelvic organ cross-sensitization.RESULTS: Bladder and bowel problems commonly co-occur in adults and children across different disorders, and the mechanism responsible for overlapping dysfunction is uncertain in most instances. At a neuronal level, cross-sensitization occurs as a result of afferent signaling from the LUT and lower bowel through different central and peripheral mechanisms. Studies in animals and humans have demonstrated evidence for cross-organ sensitization following experimental inflammation or distension of the lower bowel, affecting the LUT. Nerve stimulation is an effective treatment for different functional LUT and bowel disorders, and whether this treatment may influence cross-organ sensitization remains uncertain. The role of physiologically dormant C-fibers, the bladder-gut-brain axis, and gut microbiome in cross-sensitization are speculative.CONCLUSION: Recommendations for research were made to explore the role of cross-organ sensitization in the pathogenesis of co-occurring LUT and bowel dysfunction in humans.

Background Evidence from observational studies have shown that moderate intensity physical activity can reduce risk of progression and cancer-specific mortality in participants with prostate cancer. Epidemiological studies have also shown participants taking metformin to have a reduced risk of prostate cancer. However, data from randomised controlled trials supporting the use of these interventions are limited. The Prostate cancer–Exercise and Metformin Trial examines that feasibility of randomising participants diagnosed with localised or locally advanced prostate cancer to interventions that modify physical activity and blood glucose levels. The primary outcomes are randomisation rates and adherence to the interventions over 6 months. The secondary outcomes include intervention tolerability and retention rates, measures of insulin-like growth factor I, prostate-specific antigen, physical activity, symptom-reporting, and quality of life. Methods Participants are randomised in a 2 × 2 factorial design to both a physical activity (brisk walking or control) and a pharmacological (metformin or control) intervention. Participants perform the interventions for 6 months with final measures collected at 12 months follow-up. Discussion Our trial will determine whether participants diagnosed with localised or locally advanced prostate cancer, who are scheduled for radical treatments or being monitored for signs of cancer progression, can be randomised to a 6 months physical activity and metformin intervention. The findings from our trial will inform a larger trial powered to examine the clinical benefits of these interventions. Trial registration Prostate Cancer Exercise and Metformin Trial (Pre-EMpT) is registered on the ISRCTN registry, reference number ISRCTN13543667. Date of registration 2nd August 2018–retrospectively registered. First participant was recruited on 11th September 2018.

Lower urinary tract symptoms (LUTS), consisting storage, voiding and post-micturition symptoms, is a comprehensive definition involving symptoms that may occur due to several causes. Instead of simply focusing on the enlarged prostate, more attention has to be paid to the entire urinary tract as well as multiple system comorbidities. Therefore, prostate surgery alone does not necessarily provide adequate management and cross-disciplinary collaborations are sometimes required. Based on current literature, this paper proposes the “3Bs” concept for managing non-neurogenic male LUTS, namely, “beyond prostate”, “beyond surgery” and “beyond urology”. The clinical application of the “3Bs” enables urologists to carry out integrated, individualized and precise medical care for each non-neurogenic male LUTS patient. Keywords: Male, Lower urinary tract symptoms, Benign prostatic hyperplasia, Benign prostatic obstruction, Detrusor overactivity, Detrusor underactivity, Prostate surgery, Comorbidities

Aims To present the development of the International Consultation on Incontinence Questionnaire-underactive bladder (ICIQ-UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health-related quality of life of UAB developed in-line with the Food and Drug Administration Guidance for Industry. Methods Draft items were developed following 44 semi-structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ-UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity. Results The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's alpha >= 0.85) and test-retest reliability (stable patients; intraclass correlation coefficient >= 0.88) were high. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ-UAB was refined using the evidence from all substudies. Conclusions The validity and reliability of the ICIQ-UAB were supported in a pilot study setting and the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ-UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies.

Aims SYNERGY II was a 12‐month phase III trial in patients with overactive bladder (OAB) symptoms that investigated the safety and efficacy of the combination of mirabegron and solifenacin in comparison with each monotherapy. This analysis evaluated the trial findings using four age subgroups (1 bpm were noted in the combination and mirabegron younger age groups only. No clinically significant findings were observed in the other safety parameters. The efficacy variables improved with all treatments and the greatest improvements were typically observed with combination therapy. Conclusions Mirabegron and solifenacin combination therapy was a well‐tolerated and effective treatment for patients with OAB symptoms irrespective of their age.

Aims To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. Methods This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. Results The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. Conclusions The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.

Introduction To ensure quality, the International Continence Society recommends asking the patient to cough every minute or 50 ml of infused volume. However, on occasions, it was noticed that if cough transmission was poor, Valsalva maneuvers could show pressure transmission was satisfactory. Hence, a study was designed to compare the two methods. Methods Cough and Valsalva maneuver pressures were compared in 40 patients, 20 consecutive men and 20 consecutive women, undergoing urodynamics at three time points: baseline (20 ml filling), prevoid and postvoid. Results At baseline, the percentage difference between pabd and pves was significantly lower for Valsalva maneuvres compared with coughs for all patients (median 5.1% vs. 10.2%). This association was consistent in male patients, but not for female. At prevoid, this was reversed with coughs providing more consistent pressure spikes than Valsalva maneuvers (median 7.0% vs. 24.1%), for all patients. Postvoid, no difference was noted in either men or women. Conclusions Quality control during urodynamics is important to ensure diagnostic accuracy. This is the first study to compare two methods of quality control, coughs, and Valsalva maneuvers. Coughs are a useful indicator of pressure transmission quality at all time points throughout urodynamic studies. However, at low volumes, Valsalva maneuvers give a better indication of quality, with lower variability, whereas at cystometric capacity coughs performed better. Therefore, if poor pressure transmission occurs with cough during urodynamics, particularly at low volumes, it is recommended that a Valsalva maneuver is used to further assess whether pressure transmission and thus urodynamic quality is satisfactory.

For patients with neurogenic detrusor overactivity incontinence (NDOI), treatment with oral medications is often unsatisfactory.To assess the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) for NDOI.Two randomized, double-blind phase 3 studies (CONTENT1, NCT02660138; CONTENT2, NCT02660359) enrolled patients with NDOI who were regularly performing clean intermittent catheterization (CIC) and were inadequately managed with oral therapy. Pooled results from the first placebo-controlled treatment cycle are reported.Patients received injections of aboBoNT-A 600 U (n = 162) or 800 U (n = 161) or placebo (n = 162) into the detrusor muscle.The primary endpoint was the mean change from baseline in NDOI episodes per week at week 6. Secondary endpoints reported are the proportion of patients with no NDOI episodes, the volume per void, urodynamic parameters, and quality of life (QoL). Safety was also assessed. Statistical analyses were conducted for the pooled study populations (each aboBoNT-A dose vs placebo).At week 6, NDOI episodes per week were significantly reduced in each aboBoNT-A group versus placebo (both p0.001) and the volume per void had significantly increased. Approximately one-third of patients in each aboBoNT-A dose group reported no NDOI episodes versus 3% of patients in the placebo group. Reductions in urinary incontinence (UI) were reflected in significantly greater improvements in UI-related QoL in the aboBoNT-A groups versus placebo. Urodynamic parameters (bladder capacity and detrusor pressure) were significantly improved with each aboBoNT-A dose versus placebo. Each aboBoNT-A dose was well tolerated. Symptomatic urinary tract infection was the most frequent treatment-emergent adverse event, with incidence comparable across the aboBoNT-A and placebo groups. The studies were terminated prematurely owing to slow recruitment and were not designed for statistical comparison between the two aboBoNT-A doses.Intradetrusor aboBoNT-A is an effective treatment and alternative option for patients with NDOI who have an inadequate response to oral anticholinergics and are already performing CIC.In patients with bladder muscle overactivity caused by neurological conditions (multiple sclerosis or spinal cord injury) and resulting in urinary incontinence, abobotulinumtoxinA injections improved their symptoms and bladder function, with no unexpected effects.

BackgroundStress urinary incontinence (SUI) is common after radical prostatectomy and likely to persist despite conservative treatment. The sling is an emerging operation for persistent SUI, but randomised controlled trial (RCT) comparison with the established artificial urinary sphincter (AUS) is lacking.ObjectiveTo compare the outcomes of surgery in men with bothersome urodynamic SUI after prostate surgery.Design, setting, and participantsA noninferiority RCT was conducted among men with bothersome urodynamic SUI from 27 UK centres. Blinding was not possible due the surgeries.InterventionParticipants were randomly assigned (1:1) to the male transobturator sling (n = 190) or the AUS (n = 190) group.Outcome measurements and statistical analysisThe primary outcome was patient-reported SUI 12 mo after randomisation, collected from postal questionnaire using a composite outcome from two items in validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form questionnaire (ICIQ-UI SF). Noninferiority margin was 15%, thought to be of acceptable lower effectiveness, in return for reduced adverse events (AEs) and easier operation, for the sling. Secondary outcomes were operative and postoperative details, patient-reported measures, and AEs, up to 12 mo after surgery.Results and limitationsA total of 380 participants were included. At 12 mo after randomisation, incontinence rates were 134/154 (87.0%) for male sling versus 133/158 (84.2%) for AUS (difference 3.6% [95% confidence interval {CI} –11.6 to 4.6], pNI = 0.003), showing noninferiority. Incontinence symptoms (ICIQ-UI SF) reduced from scores of 16.1 and 16.4 at baseline to 8.7 and 7.5 for male sling and AUS, respectively (mean difference 1.4 [95% CI 0.2–2.6], p = 0.02). Serious AEs (SAEs) were few: n = 6 and n = 13 for male sling and AUS (one man had three SAEs), respectively. Quality of life scores improved, and satisfaction was high in both groups. All other secondary outcomes that show statistically significant differences favour the AUS.ConclusionsUsing a strict definition, urinary incontinence rates remained high, with no evidence of difference between male sling and AUS. Symptoms and quality of life improved significantly in both groups, and men were generally satisfied with both procedures. Overall, secondary and post hoc analyses were in favour of AUS.Patient summaryUrinary incontinence after prostatectomy has considerable effect on men’s quality of life. MASTER shows that if surgery is needed, both surgical options result in fewer symptoms and high satisfaction, despite most men not being completely dry. However, most other results indicate that men having an artificial urinary sphincter have better outcomes than those who have a sling.

Urodynamic investigations are indicated when empiric or conservative treatment fails to improve a patient’s lower urinary tract symptoms and invasive treatment is considered. Based on the expected underlying lower urinary tract dysfunction, the clinician designs a urodynamic evaluation from the range of available tests, with the aim to reproduce the patient’s symptoms and to identify the underlying pathophysiological mechanisms. Other functions of the lower urinary tract are also analysed, as they may be relevant for planning and discussing further treatment options. In this book chapter, we describe the available urodynamic tests, the normal findings, and the evidence for the role of urodynamics in different lower urinary tract disorders.

Background Transurethral resection of the prostate (TURP) is the standard operation for benign prostatic obstruction (BPO). Thulium laser transurethral vaporesection of the prostate (ThuVARP) vaporises and resects the prostate using a technique similar to TURP. The small amount of existing literature suggests that there may be potential advantages of ThuVARP over TURP. Objective To determine whether or not the outcomes from ThuVARP are equivalent to the outcomes from TURP in men with BPO treated in the NHS. Design A multicentre, pragmatic, randomised controlled parallel-group trial, with an embedded qualitative study and economic evaluation. Setting Seven UK centres – four university teaching hospitals and three district general hospitals. Participants Men aged ≥ 18 years who were suitable to undergo TURP, presenting with bothersome lower urinary tract symptoms (LUTS) or urinary retention secondary to BPO. Interventions Patients were randomised 1 : 1 to receive TURP or ThuVARP and remained blinded. Main outcome measures Two co-primary outcomes – patient-reported International Prostate Symptom Score (IPSS) and clinical measure of maximum urine flow rate (Qmax) at 12 months post surgery. Results In total, 410 men were randomised, 205 to each arm. The two procedures were equivalent in terms of IPSS [adjusted mean difference 0.28 points higher for ThuVARP (favouring TURP), 95% confidence interval (CI) –0.92 to 1.49 points]. The two procedures were not equivalent in terms of Qmax (adjusted mean difference 3.12 ml/second in favour of TURP, 95% CI 0.45 to 5.79 ml/second), with TURP deemed superior. Surgical outcomes, such as complications and blood transfusion rates, and hospital stay were similar for both procedures. Patient-reported urinary and sexual symptoms were also similar between the arms. Qualitative interviews indicated similar patient experiences with both procedures. However, 25% of participants in the ThuVARP arm did not undergo their randomised allocation, compared with 2% of participants in the TURP arm. Prostate cancer was also detected less frequently from routine histology after ThuVARP (65% lower odds of detection) in an exploratory analysis. The adjusted mean differences between the arms were similar for secondary care NHS costs (£9 higher for ThuVARP, 95% CI –£359 to £376) and quality-adjusted life-years (0.01 favouring TURP, 95% CI –0.04 to 0.01). Limitations Complications were recorded in prespecified categories; those not prespecified were excluded owing to variable reporting. Preoperative Qmax and IPSS data could not be collected for participants with indwelling catheters, making adjustment for baseline status difficult. Conclusions TURP was superior to ThuVARP in terms of Qmax, although both operations resulted in a Qmax considered clinically successful. ThuVARP also potentially resulted in lower detection rates of prostate cancer as a result of the smaller volume of tissue available for histology. Length of hospital stay after ThuVARP, anticipated to be a key benefit, was equal to that after TURP in this trial. Overall, both ThuVARP and TURP were effective procedures for BPO, with minor benefits in favour of TURP. Therefore, the results suggest that it may be appropriate that new treatment alternatives continue to be compared with TURP. Future work Longer-term follow-up to assess reoperation rates over time, and research into the comparative effectiveness of ThuVARP and TURP in large prostates. Trial registration Current Controlled Trials ISRCTN00788389. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 41. See the NIHR Journals Library website for further project information.

ObjectiveProstate surgery can improve lower urinary tract symptoms (LUTS) by relieving bladder outlet obstruction (BOO). However, surgery is less effective without BOO, or if detrusor underactivity (DU) is present. Urodynamics (UDS) can identify BOO and measure detrusor activity, but evidence in clinical practice is lacking. UPSTREAM (Urodynamics for Prostate Surgery Trial: Randomised Evaluation of Assessment Methods) evaluated whether a carepathway including UDS would reduce surgery without increasing urinary symptoms.Design, setting and participantsUPSTREAM is a pragmatic, non-inferiority randomised controlled trial in 26 hospitals in England (ISRCTN56164274) in men with bothersome LUTS where surgery was an option. InterventionParticipants were randomised (1:1) to routine care (RC) diagnostic tests, or routine care plus urodynamics (UDS).Outcome measuresThe primary outcome was International Prostate Symptom Score (IPSS; patient reported outcome scale from 0 to 35 points) 18-months post-randomisation, with a non-inferiority margin of one point. Urological surgery rates were a key secondary outcome.Statistical analysisThe primary outcome was compared between the arms using linear regression, analysed on an intention-to-treat basis.Results and limitationsBetween October 2014 and December 2016, 820 men (median age 68 years) were randomised (393 and 427 in RC and UDS arms, respectively). The UDS arm showed noninferiority of mean IPSS scores (UDS 12·6; RC 13.1; adjusted difference at 18 months -0·33 (95% CI -1·47, +0·80)). In the UDS arm, 153/408 (38%) received surgery compared with 138/384 (36%) for RC (adjusted OR 1·05; 95% CI 0·77, 1·43). 428 adverse events (UDS 234; RC 194) were recorded, with related events similar in both arms, and 11 unrelated deaths.Conclusion In this population, the UDS randomised group was non-inferior to RC for IPSS but did not reduce surgical rates. The study shows that routine use of UDS in evaluation of uncomplicated LUTS has a limited role and should be used selectively. Patient summaryFor men with uncomplicated lower urinary tract symptoms, the symptom improvements after treatment and the number of operations done are similar, whether or not urodynamic tests aredone in addition to routine tests. Accordingly, routine use of UDS has a limited role in this population group.

Background Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. Objectives The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. Design This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. Setting Urology departments of 26 NHS hospitals in England. Participants Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. Interventions Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). Main outcome measures The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. Results A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (–0.33, 95% CI –1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43–44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. Limitations The trial met its predefined recruitment target, but surgery rates were lower than anticipated. Conclusions Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. Future work Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. Trial registration Current Controlled Trials ISRCTN56164274. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

Context The impact of food and drinks on body fluid metabolism is of direct clinical relevance but current evidence remains fragmented. Aim Synthesise current evidence on the role of food and drinks in urine production. Methods Systematic review as per PRISMA guidelines using MEDLINE and EMBASE databases (completed October 2019). Studies reporting on the effect of food, food constituents, and drinks on urine production were included. Two authors performed an independent extraction of relevant articles using predetermined data sets and completed quality-of-study indicators. Results A total of 49 studies were included, of which 21 enroled human subjects, and 28 were clinically relevant animal studies (all of which utilised rodent models). The included studies were determined to be of variable quality. High dietary sodium, as well as wine, spirits, high-caffeine coffee, and caffeinated energy drinks, increased urine production in human studies. Decreased urine production was associated with low dietary sodium and consumption of milk, orange juice, and high-salt/high-sugar drinks. In animal models, a variety of fruits, vegetables, herbs, spices, and honey were associated with increased urine production. Conclusion Current evidence suggests that although several types of food and drinks may impact body fluid metabolism, the quality of the data is variable. Urine production appears to be influenced by multiple factors including composition (ie, moisture, macronutrients, and electrolytes), metabolite load, and the presence of specific diuresis-promoting substances (eg, caffeine, alcohol) and other bioactive phytochemicals. Future research is needed to support current evidence and the physiologic mechanisms underlying these findings.

OBJECTIVES To evaluate the psychometric properties of a new patient-reported outcome measure (PROM), the International Consultation on Incontinence Questionnaire-Satisfaction (ICIQ-S), to assess satisfaction after urological surgery. SUBJECTS/PATIENTS AND METHODS Following item development, the developmental ICIQ-S (dICIQ-S) was used within in a randomised control trial comparing two types of surgery for male prostatic obstruction at 1.5, 3, and 12 months after surgery. Reliability was assessed by Cronbach's α and construct validity by the correlation of scores with concurrently administered PROMs of known validity: ICIQ-Male Lower Urinary Tract Symptoms (LUTS), International Prostate Symptom Score, and the ICIQ-LUTS Quality of Life. RESULTS A total of 410 men were included in the trial. Missing data was generally low for the dICIQ-S [mean (range) 1.6 (

Aims: In its 22nd year, the International Consultation on Incontinence Questionnaire (ICIQ) project continues to promote its primary objective; the development and dissemination of patient completed questionnaires for the standardized, high-quality assessment of urinary, bowel, and vaginal symptoms. The paper gives an update on the ICIQ in the context of current scientific developments of PROM design and regulatory requirements, and plans are outlined for its future direction. Methods: An online library of all questionnaires, including over 300 translations has been launched to facilitate access through a semi-automated registration system. The ICIQ project continues to update its protocol to meet current scientific standards and incorporate methodological advances within PROM development. Results: Nineteen psychometrically validated patient-reported outcome measures (PROMs) are published for use in clinical practice and research, including amongst others, a bladder diary, male and female lower urinary tract symptoms, long term catheter, pad use, and bowel symptom questionnaires. The original ICIQ-UI Short Form for the assessment of urinary incontinence continues to be the most internationally used questionnaire and has been translated into over 60 languages. New questionnaires which are under development include the ICIQ-Underactive Bladder and ICIQ-Satisfaction. We anticipate the new website and online library will further facilitate the ease of dissemination and availability of the questionnaires for clinical practice and research. Conclusion: The ICIQ continues to successfully achieve its primary objective. Going forward, a greater focus on promoting routine clinical use and the potential for electronic integration into databases and medical records is envisaged.

Aims Lower urinary tract symptoms (LUTS) can be classified into symptom syndromes based on which symptoms are predominant. Overactive bladder (OAB) syndrome, a storage dysfunction, and underactive bladder (UAB) syndrome, a voiding dysfunction, are common syndromes, which urodynamic tests may show to be caused by detrusor overactivity (DO) and detrusor underactivity (DU), but can also be associated with other urethro-vesical dysfunctions. Sometimes OAB and UAB can coexist in the same patient and, if so, need a specific approach beyond treatment of the single and apparently opposing syndromes. Methods During its 2019 meeting in Bristol, the International Consultation on Incontinence Research Society held a literature review and expert consensus discussion focused on the emerging awareness of the coexisting overactive-underactive bladder (COUB). Results The consensus considered whether COUB is the combination of OAB and UAB syndromes, or a real unique clinical syndrome in the same patient, possibly with a common etiology. Definitions, pathophysiology, diagnosis, and treatment were discussed, and high-priority research questions were identified. Conclusions COUB (with or without urodynamic evidence of DO and DU) may be considered a real clinical syndrome, because it differs from single OAB and UAB, and may not be the combination of both syndromes. Urodynamic tests may be necessary in unclear cases or in cases not responding to initial treatment of the most troublesome symptoms. It is pivotal to define the evolution of the syndrome and the characteristic population, and to recognize predictive or phenotyping factors to develop a specific approach and adequate outcome measures.

Background The long-term potential of solifenacin and mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of solifenacin succinate 5mg plus mirabegron 50mg tablets (combination treatment) versus solifenacin or mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to mirabegron and solifenacin for the number of incontinence episodes (vs mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p Conclusions Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

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