Accepted Article

Burden of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) – focus on the UK1

Mark Speakman1, Roger Kirby2, Scott Doyle3,4*, Chris Ioannou3

1

Department of Urology, Musgrove Park Hospital, Taunton, Somerset, TA1 5DA, UK;

2

The Prostate Centre, 32 Wimpole Street, London W1G 8GT, UK; 3GlaxoSmithKline,

Stockley Park West, Ironbridge Road, Uxbridge, UB11 1BT, UK; 4University of Oxford, Department of Public Health, Rosemary Rue Building, Roosevelt Drive, Oxford, OX3 7LF, UK.

*Correspondence to: Scott Doyle GlaxoSmithKline Stockley Park West Uxbridge

Middlesex

UB11 1BT

Telephone: +44 (0)208 990 4118

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bju.12745

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Accepted Article

Email: [email protected]

Word count (2500–5000 words): 4807 (abstract through to discussion)

Keywords: BPH; burden of illness; quality of life; epidemiology; economics; LUTS

Key messages



Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) can be bothersome and negatively impact on a patient’s quality of life



As the prevalence of LUTS/BPH increases with age, the burden on the healthcare system and society may increase due to the ageing population. This review unifies literature on the burden of LUTS/BPH on patients and society, particularly in the UK



LUTS/BPH is associated with high personal and societal costs, both in direct medical costs and indirect losses in daily functioning, and through its negative impact on quality of life both for patients and partners



LUTS/BPH is often underdiagnosed and undertreated. Men should be encouraged to seek medical advice for this condition and should not accept it as part of ageing, while clinicians should be more active in the identification and treatment of LUTS/BPH

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ABSTRACT Objectives 

To assess the burden of illness and unmet need arising from lower urinary

tract symptoms (LUTS) presumed secondary to benign prostatic hyperplasia (BPH) from an individual patient and societal perspective with a focus on the UK

Patients and Methods 

Embase, PubMed, the World Health Organization, the Cochrane Database of

Systematic Reviews and the York Centre for Reviews and Dissemination were searched to identify studies on the epidemiological, humanistic or economic burden of LUTS/BPH published in English between October 2001 and January 2013



Data were extracted and the quality of the studies was assessed for inclusion



UK data were reported; in the absence of UK data, European and US data

were provided

Results 

In total, 374 abstracts were identified, 104 full papers were assessed and

33 papers met the inclusion criteria and were included in the review. An additional paper was included in the review upon a revision in 2014



The papers show that LUTS are common in the UK – affecting about 3% of

men aged 45–49 years, rising to >30% in men aged 85 years and older



European and US studies have demonstrated the major impact of LUTS on

quality of life of the patient and their partner Final draft 3

This article is protected by copyright. All rights reserved.

LUTS are associated with high personal and societal costs, both in direct

Accepted Article



medical costs and indirect losses in daily functioning. While treatment costs in the UK are relatively low compared with other countries, the burden on health services is still substantial

Conclusion 

LUTS associated with BPH is a highly impactful condition which is often

undertreated



LUTS/BPH have a major impact on men, their families, health services and

society



Men with LUTS secondary to BPH should not simply accept their symptoms

as part of ageing, but should be encouraged to consult their physicians if they have bothersome symptoms

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Accepted Article

INTRODUCTION Lower urinary tract symptoms (LUTS), such as poor flow, nocturia, frequency,

urgency, dribbling and incomplete voiding, are common in older men. While LUTS may be associated with conditions such as diabetes mellitus, neurological disease or urinary tract infections, in the absence of a precipitating factor LUTS is commonly the result of benign prostatic enlargement secondary to benign prostatic hyperplasia (BPH). UK community-based studies in the 1990s of men aged 40 years and older showed a prevalence of moderate-to-severe LUTS associated with BPH of 10–41%, with increasing prevalence with older age [1-3]. These studies showed that

symptoms progressed with time in a significant proportion of men, and also highlighted the negative impact of LUTS on men’s quality of life, daily activities and general health. As the proportion of older men in the population increases, the burden of LUTS on health services and society will also potentially increase. Despite the availability of new treatments over the past 20 years, including 5-alpha reductase inhibitors and alpha blockers, men with LUTS/BPH remain underdiagnosed [4] and undertreated [5]. Unlike other chronic conditions which are commonly underdiagnosed, such as hypertension and peripheral arterial disease [6,7], LUTS are often characterised by bothersome symptoms, suggesting that men are not aware of the availability of medical treatment. BPH is a progressive disease, which if left untreated may lead to increased prostate volume, reduction in maximum urinary flow rate, and an increase in the risk of acute urinary retention (AUR) [8], a medical emergency [9]. Thus, the aim of therapy should be to provide symptom relief, improve quality of life and prevent or reduce the risk of severe BPH-related Final draft 5 This article is protected by copyright. All rights reserved.

Accepted Article

complications such as AUR. In the UK, it is estimated that more than £180 million is spent on BPH treatments each year, with approximately 60% of these costs incurred in secondary care as a direct result of managing BPH complications [10,11]. In 2000, it was estimated that the direct cost of medical services for BPH in the USA was approximately $1.1 billion, while outpatient pharmacotherapy for BPH between 1996 and 1998 amounted to $194 million annually [12]. As healthcare systems around the world face increasing cost scrutiny, a more nuanced understanding of cost-effective treatments, care pathways and resource management will be necessary to ensure high patient satisfaction and the maintenance of health outcomes in the environment of cost-containment. The current review aimed to explore recently published literature on the humanistic and economic burden of disease and unmet need associated with BPH, with a focus on the UK, but also considering data obtained in other countries in the absence of UK data. This review is the first to combine information on the burden of BPH on patients and healthcare resources and was prompted by a lack of literature unifying these various aspects of the burden of BPH on patients and healthcare resources. The review focused on LUTS associated with BPH, terms that are often used interchangeably in the literature, rather than LUTS associated with other conditions (such as overactive bladder).

METHODS

Search strategy A number of electronic databases were searched by the author SD for appropriate articles including: Embase, PubMed, the World Health Organization (WHO), the

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Cochrane Database of Systematic Reviews and the York Centre for Reviews and Dissemination (CRD). Articles were limited to English language publications, in humans, and published between October 2001 and October 2011. A second search was later conducted to update this article with literature published between November 2011 and January 2013. Search terms included: BPH, prostatic hyperplasia, benign prostate hyperplasia, benign prostatic hyperplasia, dutasteride, finasteride, 5-alpha reductase inhibitors, epidemiology, prevalence, incidence, quality of life, economics, cost of illness. These terms were free text searched as well as variations of the terms using Medical Subject Heading (MeSH), exploded terms and combined in appropriate search strings, for example: ("Prostatic Hyperplasia"[Mesh] OR "benign prostate hyperplasia" OR "benign prostatic hyperplasia") AND ("Epidemiology"[Mesh] OR "epidemiology"[Subheading] OR "Prevalence"[Mesh] OR "Incidence"[Mesh] OR "Quality of Life"[Mesh] OR "Economics"[Mesh] OR "Economics, Pharmaceutical"[Mesh]): Limits: English, human, published in the past 10 years.

Two authors (SD and CI) independently screened the abstracts of identified papers, and full text copies of all potentially relevant primary studies were obtained. Duplicate articles were removed by hand before the articles were reviewed. Reference lists of included studies were scanned to identify additional potentially relevant studies. Full details of the search strategies used are available from the authors on request (see Appendix). Studies were included in this review if they provided primary data on the economic, humanistic or epidemiological burden of BPH, were published in English, and were

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published between October 2001 and January 2013. While we aimed to focus on UK data, in the absence of UK we included European data, and in the absence of European data, we considered data from the USA. Articles were excluded if they focused on prostate cancer, surgical techniques, diagnostics, changes in symptoms associated with BPH management, genetics, alopecia, quality of life changes associated with a specific treatment (i.e. surgical, phytotherapy, pharmacotherapy or behavioural intervention), psychometrics, prevention or risk factors, letters/editorials or simple generic reviews. Articles with US costs and economics were excluded unless there was a lack of UK or European data, as it is difficult to extrapolate the results to a UK setting due to differences in healthcare and reimbursement systems. RESULTS

Search Results The initial search in October 2011 identified 286 abstracts in total which were reviewed for inclusion. From this initial abstract review, 93 full-text articles were collected for thorough assessment, including articles identified by the hand searches of bibliographies. In total, 30 articles were included in the final review. The updated search in 2013 identified 88 article abstracts, 11 full-text articles for assessment, 1 of which was included, plus 2 additional articles from the authors’ own collections. Upon revision of the review in January 2014, an additional article was identified by an author (MS).

Epidemiology

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A total of 16 studies assessing the epidemiological burden of LUTS were included (Table 1).

Epidemiological studies have revealed a high prevalence of LUTS in the community. In the UK, data from the General Practice Research Database (GPRD) from 1992 to

2001 showed an increasing prevalence of reported LUTS with older age, from 3.5% in men aged 45–49 years to >30% in men aged >85 years [13]. There was an increase in the use of medical therapy for LUTS over the period of this study; the proportion of time with LUTS increased from 10% when men were receiving treatment, with an accompanying increase in the time from first symptoms to surgery.

A similar increasing prevalence of LUTS with older age was reported in the Multinational Survey of the Aging Male (MSAM-7), which surveyed 12,815 men aged 50–80 years in the UK, USA, France, Germany, The Netherlands, Italy and Spain [14]. The survey questionnaire assessed LUTS using the International Prostate Symptom Score (IPSS), a validated symptom scale. In total, 31% of men reported moderate-to-severe LUTS (34% in the USA and 29% in Europe). Across all countries, prevalence increased from 22% in men aged 50–59 years to 45% in men aged 70–80 years (p50 years, and 5697 aged ≥65 years, respectively) [5,20,21].

LUTS/BPH are among the most frequent reasons for medical consultation among older men. In an analysis of data from US healthcare plans, BPH was the fourth most common diagnosis, after coronary artery disease (CAD) and hyperlipidaemia, hypertension and type 2 diabetes in the Integrated Health Care Information Solutions (IHCIS) database (1,134,491 men aged ≥50 years). The Medicare database (479,190 men aged ≥65 years) also placed BPH as the fourth most common condition after CAD/hyperlipidaemia, hypertension and cataracts [22]. One of the main reasons men seek clinical help for urinary tract problems is the bothersomeness of their symptoms. Data collected by the TransEuropean Research Into the Use of Management Policies for LUTS suggestive of BPH in Primary Health care project, which included 4979 patients newly presenting with LUTS from six European countries (435 from the UK), showed that 77% overall and 89% in the UK consulted their doctor due to ‘bothersomeness’ [23]. Other reasons for consultation among UK patients included fear of prostate cancer (15%), attendance through screening programme (3%) and request from family member or friend (1%). Despite improvements in medical therapy, BPH can still progress and cause serious complications, such as AUR. In a review of data from the Hospital Episode Statistics database of the Department of Health in England, a total of 165,527 men were admitted to hospital with AUR between October 1997 and September 2003, equating to an incidence of 3.06 per 1000 men per year [24]. In 65% of these cases, AUR was classified as spontaneous (i.e. primary diagnosis with no preceding hospitalisation within the last 5 days), and of these spontaneous cases, the incidence of recurrent

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AUR (rehospitalisation within 6 months) rose from 18% in 1998 to 22% in 2003, suggesting an unmet need in the treatment of BPH complications. Similarly, in the Netherlands, retrospective analysis of records of men aged ≥45 years in a primary care database (1995–2000) revealed that the incidence of AUR was 2.2 per 1000 man-years (equivalent to 0.2% of men per year) in the general population (N=56,958) and 35.9 per 1000 man-years (equivalent to 3.6% of men per year) in men newly diagnosed with BPH/LUTS (N=2214) [25]. AUR was the first presenting symptom of BPH in 49% (73/149) of men newly diagnosed with

LUTS/BPH who experienced AUR. The proportion of AUR cases that were spontaneous rather than precipitated in England was consistent with the proportion found in the multinational Reten-World cross-sectional survey conducted in 3785 men in France, Asia, Latin America,

Algeria (70% of men overall) [9]. The proportion ranged from 54% in Latin America to 83% in Algeria. Other complications of BPH include urinary infection and renal failure. In the US Nationwide Inpatient Sample of community hospital data, discharges for primary BPH with acute renal failure increased by >400% (OR 4.28, 95% CI 3.22–5.71, ptrend

Burden of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) - focus on the UK.

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) can be bothersome and negatively impact on a patient's quality ...
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