Triptorelin for the relief of lower urinary tract symptoms in men with advanced prostate cancer: results of a prospective,observational,grouped-analysis study

Abstract

Background:

Lower urinary tract symptoms (LUTSs) may develop in men with prostate cancer (PCa) and can impact quality of life (QoL). Gonadotropin-releasing hormone (GnRH) agonists as androgen deprivation therapy are standard treatment for PCa, however, data are limited on their effects on LUTSs. A grouped analysis of national observational, non-interventional studies initiated in clinical practice was performed to assess the effectiveness of triptorelin in reducing moderate or severe LUTSs, measured using the International Prostate Symptom Score (IPSS) in men with advanced or metastatic PCa.

Methods:

Men with PCa and LUTSs scheduled to receive triptorelin (3-month or 1-month extended release formulation) were recruited into prospective, non-interventional studies at centres in Algeria, Australia, Belgium, China, Hungary, Romania and South Korea. The primary effectiveness endpoint was the proportion of patients with moderate or severe LUTSs, assessed by IPSS, after 48 weeks. Secondary endpoints included: total IPSS, QoL due to urinary symptoms (IPSS Question 8) and prostate-specific antigen (PSA) levels at 24 and 48 weeks.

Results:

A total of 2701 patients were recruited; 1851 patients with moderate or severe LUTSs at baseline (IPSS > 7), received triptorelin and had follow-up IPSS (efficacy population). The proportion of patients with moderate or severe LUTSs was reduced to 67.2% from baseline at week 48, following a reduction to 75.9% at week 24: the overall time effect was significant (p < 0.001). QoL due to urinary symptoms significantly improved from a mean score of 3.7 at baseline, to adjusted means of 2.5 and 2.1, at weeks 24 and 48, respectively (p < 0.001 versus baseline). Mean PSA levels were reduced from 158.8 ng/ml at baseline to 11.5 and 16.0 ng/ml at weeks 24 and 48, respectively.

Conclusions:

Within the limitations of these observational studies, improvements in LUTSs and QoL observed after 24 weeks and maintained at 48 weeks indicate that triptorelin-induced effects improve LUTSs in patients with advanced PCa.

Keywords

androgen deprivation therapy gonadotropin-releasing hormone agonists lower urinary tract symptoms prostate cancer quality of life triptorelin

Introduction

Men with prostate cancer (PCa) may develop lower urinary tract symptoms (LUTSs) when prostate tumours invade or compress the prostatic urethra, the bladder or the neurovascular bundles, or when the prostate is enlarged.^1–3 It has been estimated that over 40% of men with PCa experience moderate or severe LUTSs.⁴ LUTSs can impact profoundly on a man’s quality of life (QoL); an effect that increases with increasing LUTS severity.⁵

Gonadotropin-releasing hormone (GnRH) agonists as androgen deprivation therapy (ADT) are the standard treatment for many patients with PCa, particularly those with advanced or metastatic disease.⁶ The impact of ADT on tumour control and achieving the reduction in prostate-specific antigen (PSA) is well established^7–9 but there is less information available on the effects on LUTSs in men with PCa. Some short-term studies of ADT with the GnRH antagonist degarelix or with ADT in the neoadjuvant setting have demonstrated reductions in LUTSs, measured by the International Prostate Symptom Score (IPSS).^10–12 There are few published data on the longer-term effects of ADT on LUTSs, apart from an earlier interim analysis of data from the current study.¹³

Triptorelin is an effective and widely used GnRH agonist for ADT in men with PCa.^14–18 The lack of data on the impact of ADT on LUTS led to the initiation of these multiple, national, observational, open-label, non-interventional studies to assess LUTSs in men starting triptorelin therapy in routine clinical practice. These studies aimed to assess the effectiveness of triptorelin in reducing LUTSs, after 24 and 48 weeks, in men with locally advanced or metastatic PCa and moderate or severe LUTSs (IPSS > 7). This report presents the final grouped analysis of these studies, the interim results of which were reported previously. In this paper, we give particular focus to the effect of changes to LUTSs on QoL due to urinary symptoms.¹³

Methods

This study was a prospective grouped analysis of data from patients participating in different non-interventional, multicentre studies with very similar protocols conducted in Algeria, Australia, Belgium, China, Hungary, Romania, and South Korea. Data were collected in a similar manner in all seven studies: any differences are noted below. The studies were non-interventional, prospective studies of LUTSs in men with locally advanced or metastatic PCa scheduled to receive triptorelin as part of a routine ADT schedule.

All studies have been completed and this grouped analysis includes all data from these studies. Details of the numbers of centres, study start dates and end dates (i.e. date of last patient, last visit) are summarized in Table 1.

Table 1.

Study centres, timing of studies and patient disposition.

Country	No. of centres	Study started	Study ended^a	Study population(N = 2701)	Effectiveness population(N = 2185)
Algeria	21	October 2008	August 2010	171	144
Australia	9	March 2011	May 2014	43	38
Belgium	26	November 2006	May 2010	325	257
China	21	June 2010	March 2014	397	277
Hungary	19	October 2009	March 2012	280	258
Romania	31	May 2009	December 2013	695	572
South Korea	21	August 2008	November 2012	790	639

Last patient, last visit.

An interim analysis of data from three studies that had completed (Algeria, Belgium, Hungary) and three that were ongoing (China, Romania, South Korea) has previously been reported by Gil and colleagues¹³ and the methodology was reported in this earlier publication. In addition, data from the Belgium study have been reported separately.¹⁹

All studies have been conducted in compliance with the Declaration of Helsinki and Good Clinical Practice guidelines. Approval was obtained from all relevant institutional review boards or independent ethics committees, and met local regulatory requirements. All patients gave written informed consent before entry into a study.

Participants

The study included men with locally advanced or metastatic PCa who were scheduled to receive triptorelin. Patients were required to be mentally and physically capable of answering the IPSS questionnaire to be eligible for inclusion. In addition, in the Australian study, patients had to have LUTSs of moderate or severe intensity. Exclusion criteria included hypersensitivity to triptorelin or its excipients; receiving GnRH agonist treatment in the previous 6 months; or a life expectancy of less than 12 months. More details on patient inclusion and exclusion criteria were reported by Gil and colleagues.¹³

The ‘study population’ was defined as all patients with total IPSS recorded at baseline. The ‘effectiveness population’ (EP) was defined as all patients from the study population who had received at least one injection of triptorelin and had at least one documented follow-up total IPSS. The analysis focusses on the EP with moderate or severe LUTSs at baseline (IPSS > 7).

Triptorelin treatment

The triptorelin treatment received in each country was dependent upon the availability of particular formulations. All patients in Australia, Hungary, Romania, South Korea, China and Algeria received the 3-month formulation of triptorelin pamoate (Decapeptyl^®/Diphereline^®) 11.25 mg every 12 weeks; and patients in Belgium could receive this formulation, or the 1-month formulation of triptorelin pamoate 3.75 mg every 4 weeks, or were switched between the formulations.

Assessments

Patients were assessed at baseline (when triptorelin was first administered), and after 24 weeks and 48 weeks of treatment. Baseline assessments included: demographic data, vital signs, previous radiation therapy, hormonal therapy or surgery for PCa, and the indication for prescribing triptorelin.

The severity of LUTSs at baseline and after 24 and 48 weeks was assessed using the IPSS questionnaire. Mild LUTSs is defined as IPSS ⩽ 7, moderate LUTSs as IPSS between 8–19, and severe LUTS as IPSS ⩾ 20. More details of IPSS were described in the Gil and colleagues paper.^13,20 QoL was assessed by one question on IPSS, which asked patients to score their condition on a scale of 0–6 (delighted, pleased, mostly satisfied, mixed, mostly dissatisfied, unhappy and terrible, respectively). If the IPSS questionnaire was incomplete for a patient at any time point, then, the total IPSS was considered to be missing at that time point.

PSA levels were measured at baseline, and after 24 and 48 weeks, where this schedule was consistent with the local standard of care. Measurements of PSA were performed in local laboratories.

Statistical analysis

The sample sizes planned in each country were based upon feasibility and were: Algeria (n = 200), Australia (n = 70), Belgium (n = 300), China (n = 500), Hungary (n = 300), Romania (n = 1500) and South Korea (n = 850). Recruitment into the study was stopped in some countries if the number of screened patients exceeded these numbers. Recruitment was stopped due to slow recruitment issues in Australia, China and Romania before the planned numbers of patients had been enrolled (see Table 1).

Primary and secondary effectiveness endpoints were based on the patients in the EP with moderate or severe LUTSs at baseline. The primary effectiveness endpoint was the proportion of patients with moderate or severe LUTSs after 48 weeks. Secondary effectiveness endpoints were total IPSS, the distribution of IPSS categories (no, mild, moderate and severe symptoms), QoL score, and PSA level at baseline, and after 24 and 48 weeks; and correlation between the change from baseline in IPSS and change from baseline in PSA level. As the Australian study did not recruit patients with mild LUTSs, data from Australian centres were excluded from some effectiveness analyses.

All analyses were performed using SAS^® version 9.2 (Cary, North Carolina, USA). The statistical tests were exploratory and two-sided at the 5% level of significance. Consequently, no adjustments for multiplicity were performed for this grouped analysis. For the primary effectiveness endpoint, the proportion of patients with moderate or severe LUTSs are presented using descriptive statistics including a 95% confidence interval (CI). The improvement in LUTSs with time was assessed using a generalized estimating equation (GEE) model and a logit link and binomial distribution. The p-value for the time-fixed effect is presented.

Similar methods based on a GEE model were used to evaluate the change in IPSS categories with time. To obtain adjusted mean of total IPSS throughout the study, a linear model with repeated measures was used, and a similar model was used for the QoL question. A repeated measures model was used to assess the effect of treatment on PSA level. Spearman’s correlation coefficient was used to assess the correlation between total IPSS and PSA.

Results

Patients

The study population (those with a total IPSS at baseline and providing informed consent) comprised 2701 men with PCa: 171 in Algeria, 43 in Australia, 325 in Belgium, 397 in China, 280 in Hungary, 695 in Romania, and 790 in South Korea (Table 1). The EP comprised 2185 patients, a total of 516 patients were excluded as they had no follow-up total IPSS and 21 of these patients had not received a triptorelin injection.

The patients’ baseline characteristics, disease characteristics, and the reason for initiating triptorelin are summarized in Table 2. Approximately 10% (189/1851) of patients in the EP had radical prostatectomy. A total of 1851 patients in the EP had moderate or severe LUTSs at baseline (IPSS > 7.0). The results presented below focus on these 1851 men in the EP with moderate or severe LUTSs.

Table 2.

Baseline patient and disease characteristics of the study population and effectiveness population.

Characteristic	Whole study population(N = 2701 unless otherwise stated)	Effectiveness population(N = 2185 unless otherwise stated)
Age (years), mean ± SD	72.1 ± 8.1*	72.2 ± 7.9
Weight (kg), mean ± SD	71.5 ± 12.2**	72.0 ± 12.1^†
Patients with metastasis (M1), n/N (%)	615/2687 (22.9)	465/2175 (21.4)
⩾T3 stage, n/N (%)	2563/2697 (95.0)	2100/2184 (96.2)
Gleason score ⩾ 8, n/N (%)	1067/2577 (41.4)	837/2101 (39.8)
PSA > 20 ng/ml, n/N (%)	1453/2614 (55.6)	1184/2135 (55.5)
Total IPSS, mean ± SD	16.4 ± 8.2***	16.3 ± 8.2^‡
IPSS category, n/N (%)
No symptoms	10/2658 (0.4)***	6/2185 (0.3)
Mild symptoms	404/2658 (15.2)***	328/2185 (15.0)
Moderate symptoms	1328/2658 (50.0)***	1106/2185 (50.6)
Severe symptoms	916/2658 (32.7)***	745/2185 (34.1)
Reason for initiating triptorelin, n/N (%)^a
Neoadjuvant before RP	49/2699 (1.8)	38/2184 (1.7)
Neoadjuvant before RT or BT	186/2699 (6.9)	170/2184 (7.8)
Adjuvant after RP	136/2699 (5.0)	103/2184 (4.7)
Adjuvant after RT or BT	50/2699 (1.9)	45/2184 (2.1)
Rising PSA level after RP	170/2699 (6.3)	129/2184 (5.9)
Rising PSA level after RT or BT	40/2699 (1.5)	30/2184 (1.4)
Locally advanced, first-line	1324/2699 (49.1)	1082/2184 (49.5)
Locally advanced, after anti-androgen	203/2699 (7.5)	163/2184 (7.5)
Metastatic, first-line	555/2699 (20.6)	437/2184 (20.0)
Other	12/2699 (0.4)	10/2184 (0.5)

Patients may have more than one reason for initiating triptorelin.

n = 2700; **n = 2091; ***Excludes data from Australia (n = 2658); ^†Excludes data from Australia n = 1685; ^‡ Excludes data from Australia n = 2147.

BT, brachytherapy; IPSS, International Prostate Symptom Score; LUTS, lower urinary tract symptom; PSA, prostate-specific antigen; RP, radical prostatectomy; RT, radiation therapy; SD, standard deviation.

Most patients received concomitant medication for LUTSs or PCa over the course of the study. Alpha-adrenoreceptor antagonists were the most frequently used treatments for LUTSs, in 17.6% of patients, and 4.9% received urinary antispasmodics (Table 3). Only around 1% of patients in the whole population received testosterone-5-alpha reductase inhibitors.

Table 3.

Concomitant medication for LUTSs at any time, study population (N = 2701).

Concomitant medication or therapy	Number of medications, n	Patients, n (%)
Alpha-adrenoreceptor antagonists	539	477 (17.6)
Alfuzosin	32	31 (1.1)
Alfuzosin hydrochloride	64	59 (2.2)
Doxazosin	9	9 (0.3)
Doxazosin mesilate	28	28 (1.0)
Naftopidil	1	1 (<0.1)
Silodosin	18	18 (0.7)
Tamsulosin	182	176 (6.5)
Tamsulosin hydrochloride	167	159 (5.9)
Terazosin	1	1 (<0.1)
Terazosin hydrochloride	37	35 (1.3)
Urinary antispasmodics	164	137 (4.9)
Fesoterodine	3	3 (0.1)
Fesoterodine fumarate	28	28 (1.0)
Floxavoxate hydrochloride	2	2 (<0.1)
Oxybutynin hydrochloride	10	10 (0.4)
Propiverine	6	6 (0.2)
Propiverine hydrochloride	34	32 (1.2)
Solifenacin	13	13 (0.4)
Solifenacin succinate	61	61 (2.3)
Tolterodine	2	2 (<0.1)
Tolterodine l-tartrate	3	3 (0.1)
Trospium chloride	1	1 (<0.1)
Trospium chloride plus sabal dry extract	1	1 (<0.1)
Testosterone-5-alpha inhibitors reductase inhibitors	29	29 (1.1)
Dutasteride	19	19 (0.7)
Finasteride	7	7 (0.3)
Testosterone-5-alpha reductase inhibitors. NOS	2	2 (<0.1)

LUTS, lower urinary tract symptom; NOS, not otherwise specified;

Effect of triptorelin on LUTSs

At week 48, the proportion of patients in the EP with moderate or severe LUTSs was reduced from 100% at baseline to 67.2% (primary effectiveness endpoint). The proportion of patients with moderate or severe LUTSs was also reduced (75.9%) at week 24. The change of intensity of LUTSs over the course of the study was significant (p < 0.001). The proportions of patients with severe, moderate, or mild LUTSs, or no symptoms after 24 weeks, 48 weeks and at the last available visit are shown in Figure 1.

Figure 1.

LUTSs by severity (according to total IPSS) at baseline, week 24, week 48 and last available visit in all patients in the effectiveness population with moderate or severe LUTSs at baseline.

Of the 1106 patients in the EP with moderate LUTSs at baseline, symptoms were reduced in severity (mostly to mild LUTSs) in approximately 30% of patients after 24 weeks and almost 40% of patients after 48 weeks of treatment [Figure 2(a)]. Of the 745 patients in the EP with severe LUTSs at baseline, triptorelin treatment reduced the severity of symptoms in almost 75% of patients after 24 weeks and over 80% of patients after 48 weeks [Figure 2(b)]. Approximately 23% of men with severe LUTSs at baseline had mild LUTSs or no symptoms after 48 weeks’ treatment with triptorelin [Figure 2(b)].

Figure 2.

LUTS severity status (according to total IPSS) at each time point in the effectiveness population with (a) moderate LUTSs at baseline (n = 1106) and (b) severe LUTSs at baseline (n = 745).

The adjusted mean total IPSS was significantly reduced from baseline in the EP at week 24 and week 48 (Table 4). The adjusted mean scores for all individual questions (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia) were also significantly reduced (p < 0.001 baseline versus week 24 and 48; Table 3).

Table 4.

Mean responses to the IPSS questionnaire individual questions (responses on a 6-point scale; 0 = not at all, 5 = almost always) in the effectiveness population in patients with moderate or severe LUTSs at baseline.

Question	Baseline	Week 24*	Week 48*	Last available visit
	Mean (95% CI) (n = 1851)^†
Incomplete emptying	2.6(2.5–2.6)	1.7(1.6–1.8)	1.5(1.4–1.6)	1.5(1.4–1.6)
Frequency	2.7(2.6–2.8)	1.9(1.8–1.9)	1.7(1.6–1.7)	1.7(1.6–1.7)
Intermittency	2.4(2.3–2.5)	1.6(1.5–1.7)	1.4(1.3–1.5)	1.4(1.3–1.5)
Urgency	2.5(2.4–2.6)	1.7(1.6–1.8)	1.5(1.4–1.6)	1.5(1.4–1.6)
Weak stream	3.1(3.0–3.1)	1.9(1.8–2.0)	1.7(1.6–1.8)	1.8(1.7–1.8)
Straining	2.2(2.2–2.3)	1.4(1.3–1.5)	1.2(1.2–1.3)	1.3(1.2–1.3)
Nocturia	2.9(2.9–3.0)	2.2(2.2–2.3)	2.0(2.0–2.1)	2.1(2.0–2.1)
Total IPSS	18.4(18.1–18.7)	12.4(12.0–12.8)	11.0(10.7–11.4)	11.2(10.9–11.5).

p < 0.001 for all questions for baseline versus week 24 and baseline versus week 48; ^†adjusted mean values for week 24 and 48.

Quality of life

At baseline, patients in the EP with moderate or severe LUTSs had a mean score of 3.7 (95% CI 3.7–3.8) for QoL due to urinary symptoms (IPSS Question 8). There were significant reductions in the adjusted mean QoL score at 24 and 48 weeks (p < 0.001 for both versus baseline; Figure 3) showing an improvement in QoL related to urinary symptoms. The adjusted mean change in the QoL score from baseline was −1.2 (95% CI −1.3 to −1.1; p < 0.001) at week 24 and −1.6 (95% CI −1.6 to −1.5: p < 0.001) at week 48. A mean change of −1.5 (95% CI −1.6 to −1.4) was reported at the last available visit. QoL was significantly improved at 24 and 48 weeks in each country in the patients with LUTSs of any intensity at baseline (Figure 4).

Figure 3.

QoL due to urinary symptom score (Question 8 on IPSS): responses on a 7-point scale; 0 = delighted, 6 = terrible) in the effectiveness population in patients with moderate or severe LUTSs at baseline.

Figure 4.

Mean change from baseline by country* in QoL due to urinary symptom score (Question 8 on IPSS) in the patients with LUTSs of any intensity at baseline.

Changes in PSA level

Mean PSA level in the EP was significantly reduced at weeks 24 and 48 (Figure 5; p < 0.001 overall time effect).

Figure 5.

Mean PSA levels for the effectiveness population with moderate or severe LUTSs at baseline.

There was a significant (p < 0.001), though weak, correlation between total IPSS change from baseline and change in PSA level from baseline at week 24, week 48 and last available visit (correlation estimates were 0.2, 0.3 and 0.2, respectively).

Discussion

The efficacy of triptorelin as ADT in men with PCa is well established, however, there has been little published on the benefits in the relief of bothersome LUTSs and associated QoL.^14–18 This grouped analysis of 2701 men with locally advanced or metastatic PCa, based on data from seven countries in distinct geographical regions, is the largest study in this patient population to demonstrate the effectiveness of triptorelin against LUTSs. This final analysis of the results confirms the previous interim assessment of data from this grouped analysis, showing that the number of patients with moderate or severe LUTSs was significantly reduced and that improvement was maintained for up to 48 weeks.¹³ These findings were reflected in another report on the data from the Belgian study by Peltier and colleagues.¹⁹ The results suggest that the impact of triptorelin treatment on LUTSs is similar across the individual countries in four different continents. In this final analysis, the proportion of patients with moderate or severe LUTSs was reduced at week 48 by approximately 33% from baseline, PSA reductions were maintained throughout the course of the study and QoL associated with urinary symptoms improved significantly.

Comparisons with previously published studies are problematic due to differences in patient populations and settings.^10–12 Nevertheless, in this grouped analysis, in which almost 70% of patients received triptorelin as first-line therapy, the mean reduction in total IPSS of 7.5 points appeared at least as great as the reductions of 0.5–3.5 points reported in patients who received goserelin in the neoadjuvant setting¹² and of 4.5–9.6 points with goserelin in patients with more severe disease.¹⁰ The length of follow up in previous studies was 12 weeks, however, this analysis demonstrates that the benefits of GnRH agonists in reducing the severity of LUTSs are sustained over a longer duration of up to 48 weeks.

LUTSs have a significant impact on men’s QoL, and the impact increases with symptom severity.⁵ Triptorelin treatment produced a reduction in the mean score on the QoL question on the IPSS questionnaire from 3.7 (a score of ⩾3.0 to <4.0: ‘mixed about equally satisfied and unsatisfied’) at baseline to 2.5 and 2.1 (a score of ⩽2.0 ‘mostly satisfied’) after 24 and 48 weeks of triptorelin treatment, respectively. The change in QoL score among patients that started triptorelin therapy represents an important improvement in QoL towards ‘mostly satisfied’.²¹ The improvements in the QoL score appeared to correspond with the improvements in LUTSs severity. There are limited data on the impact of GnRH analogues on QoL to compare with our findings. A recent study in Germany that included 608 men with advanced PCa treated with triptorelin over 1 year, reported that QoL, assessed by various validated questionnaires, was generally stable over the course of treatment, although clinically relevant improvements were observed in around a quarter of patients.²² Previously, in the comparative study between the GnRH agonist goserelin and the GnRH antagonist degarelix, both treatments were associated with significant increases in QoL due to improvements in urinary symptoms.¹⁰

The effects of GnRH agonists on LUTSs have been suggested to be a result of prostate volume reduction, rather than a result of tumour volume reduction.^12,23 There was a clear correlation between PSA suppression and LUTS improvement in this large cohort of patients, although prostate volume was not directly measured in this observational study. A minority of patients (less than approximately 20%) received concomitant medication for LUTSs during the study. The study was not designed to assess the relative impact that these co-medications may have had on the severity of LUTSs. In this study, only a small proportion of patients underwent transurethral resection of the prostate (TURP), which is unlikely to affect the overall change of IPSS observed with triptorelin.

An important advantage of this study is the routine clinical setting, which gives an indication of the impact of ADT on LUTSs in a heterogeneous population in several countries. Other strengths of this analysis are the inclusion of a larger population than had previously been assessed for the impact of ADT on LUTSs and a longer time-scale than previous studies.^10–12,24 Observational studies do, however, have inherent limitations, including a potential for selection bias and a lack of control for confounding factors, such as the impact of concomitant medications or TURP for LUTSs, or likewise the impact that the 10% of patients that had radical prostatectomy (which generally improves LUTSs) may have had on outcomes, which we acknowledge here. In addition, this study does not include a comparative/control arm, and the data do not allow for a comparison between triptorelin and other medications for LUTSs. The lack of IPSS analyses according to PSA levels is also a weakness of the study. Moreover, the IPSS questionnaire relies on the patient’s ability to recall and record symptoms, which could result in over- or under-estimation of these symptoms. The IPSS, however, is used widely for the assessment of LUTSs and consequently provides a useful tool for comparing the results of this grouped analysis with other studies.

In conclusion, the results of this observational study provide evidence for the effectiveness of triptorelin in reducing LUTSs severity in men with advanced PCa, notwithstanding the limitations of the study design. Significant improvements in QoL from baseline appeared to correspond with the improvements in LUTS severity. The improvement in LUTSs and QoL were observed after 24 weeks and maintained at 48 weeks, which may indicate that, as anticipated, triptorelin-induced prostatic atrophy is effective in improving LUTSs in this group of patients.

Footnotes

Acknowledgements

These studies and this analysis were funded by Ipsen Pharma, France, in the respective countries. The authors take full responsibility for the content of the paper but thank Martin Gilmour and Tim Latham of ESP Bioscience, Crowthorne, UK (supported by Ipsen) for editorial assistance in the preparation of the manuscript. The authors thank all investigators who gathered data for this analysis.

We would like to thank all participating centres in Algeria, Australia, Belgium, China, Hungary, Romania and South Korea who have enrolled patients into the local LUTS studies. We would also like to thank all the patients who agreed to participate in the study.

Funding

These studies and this analysis were funded by Ipsen in the respective countries. Editorial assistance in the preparation of this manuscript was also supported by Ipsen.

Conflict of interest statement

Roland van Velthoven is a consultant for Ipsen. Thierry Gil and Fouad Aoun have no financial interest or financial conflict with the subject matter or materials discussed in the manuscript. Patrick Cabri and Valérie Perrot are employees of Ipsen.

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