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european urology supplements 7 (2008) 680–689
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Lower Urinary Tract Symptoms Suggestive of Benign Prostatic
Hyperplasia (LUTS/BPH): More Than Treating Symptoms?
Mark J. Speakman *
Musgrove Park Hospital, Taunton & Somerset NHS Foundation Trust, Taunton, Somerset TA1 5DA, United Kingdom
Article info
Abstract
Keywords:
Acute urinary retention
Aetiology
Benign prostatic hyperplasia
Pathogenesis
Progression
Quality of life
Treatment
Context: During the last two decades, it has become clear that the management of lower urinary tract symptoms associated with benign prostatic
hyperplasia (LUTS/BPH) is much more than just treating symptoms.
Objective: This review paper gives an overview of the main factors
influencing individual treatment decisions for LUTS/BPH patients.
Evidence acquisition: This paper summarizes the content of an update
lecture held during a symposium on the management of LUTS/BPH at the
2008 European Association of Urology meeting. During the presentation,
the current decision drivers were discussed based upon recent literature
and illustrated with the results of a Web-based survey evaluating urologists’ opinions on LUTS/BPH management.
Evidence synthesis: The treatment of choice depends on the severity and
type of LUTS, which are nowadays believed to have a multifactorial
aetiology. Consequently, treatment for LUTS/BPH should not focus merely
on the prostate, but also on other organs involved in disease pathogenesis.
In addition, the progressive character of LUTS/BPH is an important driver
when taking treatment decisions. Patients at low risk of disease progression require a fast and sustained symptom relief with minimal treatment
morbidity, while patients at high risk of progression additionally require
continuous treatment delaying LUTS/BPH progression and the development of complications. Therefore, clinicians should be able to determine a
patient’s individual risk of progression. At present, seven baseline parameters and three dynamic variables have been identified as predictors of
LUTS/BPH progression. Furthermore, as the quality of life (QoL) of both
patients and their partners is severely affected by LUTS/BPH, this aspect
should also be considered. Finally, treatment decisions are also influenced
by existing comorbidities in the patient.
Conclusions: Treatment for LUTS/BPH should aim at relieving the symptoms and especially at improving the patient’s QoL with minimal treatment morbidity. Furthermore, LUTS/BPH treatment should be adapted to
the patient’s individual risk of disease progression.
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# 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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doi:10.1016/j.eursup.2008.08.003
european urology supplements 7 (2008) 680–689
1.
Introduction
Benign prostatic hyperplasia (BPH) is a disorder that
is macroscopically characterized by an enlargement
of the prostate gland and histologically caused by
the progressive hyperplasia of stromal and glandular prostatic cells. This nonmalignant overgrowth
of prostatic tissue might ultimately lead to constriction of the urethral opening. Consequently, clinical
BPH is often associated with lower urinary tract
symptoms (LUTS). In fact, BPH is the main cause of
LUTS in ageing men. About half of the male
population over the age of 50 can be diagnosed
with histological BPH, and this prevalence increases
with age to about 90% over the age of 80 [1].
Clinically, about one-third of men in their sixth
decade of life suffer from moderate-to-severe LUTS,
and this percentage rises to about 45% in men older
than 70 [2].
The classical treatment for LUTS/BPH mainly
focused on symptom relief by surgical removal
of the enlarged prostate, thereby relieving urinary
outflow obstruction [3]. However, during the
last two decades, it has become clear that the
management of LUTS/BPH—either by watchful
waiting, by pharmacological treatment with
a1-adrenoceptor (a1-AR) antagonists and/or 5areductase inhibitors, or by (minimally invasive)
surgery—is much more than just treating symptoms. To date, four modern drivers for taking
individual treatment decisions for LUTS/BPH can
be discerned.
In this paper, the impact of the multifactorial
aetiology and the progressive character of LUTS/
BPH on the management of this condition will
be discussed. In addition, the risk factors for
disease progression, as well as additional factors
influencing individual treatment decisions, will be
reviewed.
2.
Evidence acquisition
This paper summarizes the content of an update
lecture held during the symposium ‘‘The future of
LUTS/BPH: management beyond the prostate’’ at
the annual meeting of the European Association of
Urology in 2008. During the presentation, an
overview of the current drivers for taking individual treatment decisions on LUTS/BPH was given
based on recent literature. Furthermore, the
results of a Web-based survey evaluating urologists’ opinions on the management of LUTS/BPH
were used to illustrate the key points of the
presentation.
3.
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Evidence synthesis
3.1.
Lower urinary tract symptoms suggestive of benign
prostatic hyperplasia have a multifactorial aetiology and a
progressive character
3.1.1. Multifactorial aetiology of lower urinary tract
symptoms suggestive of benign prostatic hyperplasia
Lower urinary tract symptoms secondary to BPH can
generally be classified as voiding symptoms (previously called obstructive), storage symptoms (previously called irritative), and post-micturition
symptoms [4].
Voiding symptoms such as slow stream, splitting
or spraying of the urine stream, intermittent
stream, hesitancy, straining, and terminal dribble
are believed to result from obstruction at the level
of the prostate. This obstruction can be caused by
an increase in prostate volume (mechanic or
static component of obstruction) and/or by an
increased smooth muscle contraction in the prostate, bladder neck, and urethra (dynamic component of obstruction).
In contrast, storage symptoms such as nocturia,
urgency, increased daytime frequency, and urinary
incontinence are thought to have a more complex
aetiology [3,5]. For a long time, these symptoms were
believed to result from obstruction- and/or ageinduced detrusor instability (see 3.1.2.1.) [6,7].
However, it has now become clear that extraprostatic mechanisms such as stimulation of a1-ARs in
the bladder, and especially the a1D-AR subtype,
which predominates in the human detrusor, also
play a role in the development of storage symptoms
[5,8,9]. However, further studies are needed to define
exactly the role of these receptors in humans.
In addition, a1-ARs located in peripheral ganglia
and/or spinal cord segments are also thought to
contribute to the aetiology of LUTS/BPH. They might
facilitate the release of acetylcholine, resulting in
the activation of muscarinic receptors in the
detrusor, increased bladder contractions, and the
concomitant development of storage symptoms [5].
Furthermore, bladder muscarinic receptors and
purinergic receptors themselves might also play a
role in the pathogenesis of LUTS, as witnessed by the
effectiveness of antimuscarinic agents in the treatment of overactive bladder (OAB) and by the changes
in muscarinic and purinergic receptor expression in
OAB (idiopathic or induced by bladder outlet
obstruction) [9–12].
Finally, several other factors have been suggested
to affect bladder function and to contribute to LUTS,
such as the endocrine, renal, and cardiac systems
[3,9].
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european urology supplements 7 (2008) 680–689
In conclusion, it is clear that not only obstruction
at the level of the prostate, but many other, often
overlapping, factors are also involved in the aetiology of LUTS/BPH. Therefore, treatment should not
only focus on the prostate, but should also take the
other players in the pathogenesis of the disease into
account.
3.1.2. Progressive character of lower urinary tract symptoms
suggestive of benign prostatic hyperplasia
3.1.2.1. Progressive cellular changes in the bladder
Although the bladder is one of the aetiological factors
in the development of LUTS/BPH, the organ itself also
suffers from outlet obstruction. Indeed, following
partial outlet obstruction, the bladder undergoes
progressive pathological changes in which three
distinct phases can be discerned [6,13,14].
As an initial response to the progressive increase
in urethral resistance, the bladder reacts with
hypertrophy of smooth muscle cells, urothelial
and interstitial fibroblast hyperplasia, and increased
collagen synthesis and deposition. Together, these
events result in a progressive increase in bladder
mass during this initial stage. As soon as the bladder
mass is sufficient to maintain detrusor contractility
and bladder emptying, the bladder enters the
compensated stage. In this phase, bladder mass
remains stable, but the progressive changes in
cellular structure and function still continue.
Finally, these alterations interfere with the compensatory mechanisms, resulting in destabilization
of bladder function and in the initiation of the
decompensated phase. This final stage is characterized by a further increase in bladder mass and a
progressive decrease in smooth muscle in the
bladder wall, leading to a deterioration of bladder
contractility. In addition, the increase of connective
tissue negatively affects bladder elasticity. Therefore, end-stage decompensated bladders have a
poor contractile function and/or poor compliance.
These progressive pathological processes in the
bladder might not only be evoked by chronic outlet
obstruction, but also by age-related changes in the
lower urinary tract. Indeed, increasing age was
shown to be associated with a decrease in detrusor
contractility, bladder capacity, and ability to withhold voiding and an increase in postvoid residual
(PVR). Moreover, the prevalence of detrusor overactivity and nocturia increases with age [7].
In animal models, these pathological events have
been shown to be reversible as long as the bladder is
in the compensated stage [13]. However, as soon as it
enters the decompensated stage, removal of partial
outlet obstruction only induces a partial recovery of
bladder function proportional to the level of decom-
pensation. Finally, when decompensation progresses beyond a critical point, bladder damage
becomes irreversible, and bladder dysfunction proceeds to end-stage decompensation.
In the long term, this obstruction- and/or ageinduced bladder damage can result in the development of serious complications in humans such as
urinary tract infections, bladder stones, acute
urinary retention (AUR), or renal failure [14].
From the aforesaid, it is clear that LUTS/BPH have
a progressive character, at least in some of our
patients. Therefore, it is important to initiate
treatment at an early stage in those patients at risk,
when pathological changes are still reversible. Only
in this way can bladder function be maintained and
disease progression and the development of serious
complications be avoided.
3.1.2.2. Natural history of lower urinary tract symptoms
suggestive of benign prostatic hyperplasia: incidence of clinical
progression events
The importance of early treatment initiation for
LUTS/BPH is further underscored by the substantial
incidence of disease progression events in the
general population, which can be assessed either
from longitudinal community-based studies or from
placebo arms of controlled trials.
One of the longitudinal studies that provided the
largest body of evidence was the Olmsted County
study, in which a randomly selected cohort of 2115
middle-class North American Caucasian men aged
40–79 yr was followed. In this study, severity of LUTS
was significantly increased at follow-up, as illustrated by the progression of 22% of men with mild
symptoms at baseline to moderate-to-severe symptoms after 42 mo and by a mean annual increase in
International Prostate Symptom Score (IPSS) of 0.18
points [15]. Moreover, median peak urinary flow rate
(Qmax) also decreased by 2.1% per year [16], while
prostate volume was significantly increased at
follow-up (average annual growth of 1.6%) [17].
However, serious outcomes such as AUR and the
need for BPH-related surgery occurred rather infrequently in the general population, as indicated by a
cumulative incidence of AUR of 2.7% over 4 yr [18].
Comparable results, showing a clear deterioration
of symptoms but a low incidence of serious complications such as AUR, were also obtained from several
other longitudinal population-based studies [19–21].
This progressive character of LUTS/BPH and the
main contribution of symptom worsening to overall
clinical progression was also confirmed in the
placebo arm of the Medical Therapy Of Prostatic
Symptoms (MTOPS) study [22]. This double-blind
controlled trial, following a total of 3047 men aged
european urology supplements 7 (2008) 680–689
50 yr with moderate-to-severe LUTS and a Qmax of
4–15 ml/s, was designed to assess the impact of
medical therapies on the risk of BPH progression. The
cumulative incidence of overall clinical progression
(defined as the first occurrence of a 4-point increase
in IPSS, AUR, urinary incontinence, renal insufficiency, or recurrent urinary tract infection) appeared
to be 16.6% over 4 yr. Symptom deterioration
accounted for the largest proportion (79.5%) of these
progression events, while AUR (14.8%, corresponding
to a cumulative incidence of 2.4% over 4 yr),
incontinence (4.9%), and urinary tract infection or
urosepsis (0.8%) occurred less frequently.
From the studies described above, it is clear that—
despite the low incidence of serious progression
events such as AUR and BPH-related surgery—
disease progression occurs significantly in patients
with LUTS/BPH when left untreated. Since reversion
of the pathological bladder changes underlying these
progression events becomes impossible beyond a
certain point, treatment should aim at preventing
progression of LUTS/BPH at an early disease stage.
Consequently, medical physicians should be able to
determine a patient’s individual risk of disease
progression before taking treatment decisions. The
currently known risk factors for progression of LUTS/
BPH, as well as other modern drivers for taking
decisions in the management of the disease, will be
discussed extensively in the next section.
3.2.
Modern drivers for taking individual treatment
decisions
3.2.1. Risk factors for the progression of lower urinary tract
symptoms suggestive of benign prostatic hyperplasia
Until now, seven parameters have been described to
be predictors of LUTS/BPH progression at baseline;
that is, age, severity of LUTS at baseline, prostate
volume, prostate-specific antigen (PSA) levels, Qmax,
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PVR, and prostatic inflammation. In addition, three
dynamic variables have been recognized as predictors of future disease-related events [23].
Convincing evidence that the baseline parameters age, severity of symptoms, prostate volume,
Qmax, and PVR have a predictive value for the risk of
LUTS/BPH progression was obtained from the
Olmsted County Study. The relative risk of AUR
was shown to be increased about eight times in men
aged 70–79 yr compared to men aged 40–49 yr.
Furthermore, a more than three times increased
relative risk of AUR was observed for men with
moderate-to-severe symptoms compared to men
with mild LUTS, while men with a prostate volume
>30 ml had a threefold increased relative risk of
AUR. In addition, a baseline Qmax 12 ml/s increased
the relative risk of AUR about fourfold [18], and a PVR
>50 ml augmented this risk about three times [24].
The findings of this longitudinal communitybased study were subsequently confirmed in the
placebo arms of several controlled studies, such as
the MTOPS study [22,25] and the PROSCAR LongTerm Efficacy and Safety Study (PLESS), a finasteride
study which enrolled 3040 men in the US with
moderate-to-severe LUTS, Qmax <15 ml/s, and an
enlarged prostate [26]. Moreover, two new baseline
variables were identified as predictors of LUTS/BPH
progression in these studies; that is, PSA levels and
prostatic inflammation.
Serum PSA was demonstrated to be a powerful
predictor of the risk of AUR and the need for BPHrelated surgery in men with BPH in the PLESS trial,
showing an increase in 4-yr cumulative incidence of
AUR from approximately 6.5% in men with a serum
PSA level <1 ng/ml to about 14% in men with PSA
levels >7 ng/ml [26]. The predictive character of PSA
levels and prostate volume was subsequently confirmed in a larger multinational patient population
[27] (Fig. 1).
Fig. 1 – Impact of baseline prostate-specific antigen (PSA) levels and prostate volume on the risk of developing acute urinary
retention (AUR). Data are obtained by pooling the results of three identical 2-yr multinational non-US finasteride-controlled
trials (SCAndinavian Reduction of the Prostate study [SCARP], PROscar Safety Plus Efficacy Canadian Two-year study
[PROSPECT], and PROscar Worldwide Efficacy and Safety Study [PROWESS]) in men with mild-to-moderate symptomatic
benign prostatic hyperplasia (BPH) [27]. The percentage of patients in the placebo group developing AUR during follow-up is
depicted as a function of baseline PSA level and prostate volume. High baseline PSA levels and large prostate volumes
significantly increase the incidence of spontaneous AUR.
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european urology supplements 7 (2008) 680–689
Inflammation has been thought to be involved in
the pathogenesis of LUTS/BPH for over a decade.
This idea was based on the observation that
prostatic inflammation and LUTS/BPH frequently
occur together [28,29]. However, only recently,
inflammation was also suggested to be an independent risk factor for disease progression. The most
convincing evidence for this hypothesis came from
the MTOPS study [30]. Examination of baseline
prostate biopsies in a subgroup of 1197 patients
showed the presence of an acute and/or chronic
infiltrate in 45% of men. In the placebo group, these
men—who also had larger prostate glands and
higher PSA values—displayed a remarkably faster
progression rate over time than men without
inflammation, as witnessed especially by the significantly higher incidence of AUR in these patients
(Fig. 2).
Further support for these data was provided by
several recent studies. Analysis of the baseline data
from the REduction by DUtasteride of prostate
Cancer Events (REDUCE) trial, a randomized double-blind placebo-controlled study in 8224 men
evaluating the effects of 0.5 mg dutasteride once
daily on reducing the risk of prostate cancer, showed
a weak but statistically significant correlation
between the degree of histological chronic inflammation and the degree of LUTS [31].
Furthermore, by examination of longitudinal data
from the Olmsted County Study, it was demonstrated
that physician-diagnosed prostatitis is associated
Fig. 2 – Impact of acute and/or chronic inflammation on the
risk of clinical progression of benign prostatic hyperplasia
(BPH): results from the Medical Therapy Of Prostatic
Symptoms (MTOPS) study [30]. The percentage of patients
experiencing overall clinical progression, acute urinary
retention (AUR), or BPH-related surgery during follow-up
(mean duration 4.5 yr) is compared between patient
groups with (n = 544) and without inflammation (n = 653)
on baseline biopsies. The risk of AUR is significantly
increased in patients with baseline inflammation, while
overall clinical progression also tends to be increased in
these patients.
with a more than twofold increased risk of later
development of BPH-associated events (prostatitis,
enlarged prostate, or BPH) and a greater risk of
requiring later treatment (medication or surgery) for
BPH [32].
Finally, the role of inflammation in the pathogenesis and progression of BPH was confirmed in a
single-centre, retrospective study in 406 patients
undergoing transurethral resection of the prostate
for AUR or LUTS. Men with acute and/or chronic
intraprostatic inflammation were shown to have a
greater risk of AUR than men without inflammation
[33].
Although all these data are in line with inflammation being a risk factor for disease progression,
more studies are needed to confirm this hypothesis.
In this regard, the longitudinal 4-yr follow-up in the
REDUCE study might provide useful information. In
addition, as daily use of nonsteroidal anti-inflammatory drugs has already been shown to be
inversely related to the onset of moderate-to-severe
LUTS, low Qmax, increased prostate volume, and
elevated PSA levels in the Olmsted County Study
[34], the potential of anti-inflammatory agents in the
prevention of LUTS/BPH progression needs to be
further evaluated.
Next to these seven baseline variables, three
dynamic variables have been identified as predictors of LUTS/BPH progression; that is, deterioration
of LUTS over time, increase in PVR over time, and
symptom deterioration and/or increasing bother
while receiving treatment [23].
Progressive deterioration of symptoms was first
recognized as a risk factor for LUTS/BPH progression
in the Health Professionals Follow-up study, a
prospective cohort study analyzing the incidence
of AUR among 6100 male US health professionals
aged 45–83 yr. In this study, the risk of AUR was
shown to be increased two- to threefold in men who
had a worsening of LUTS during the 2-yr follow-up
period. Moreover, this risk seemed to be independent of baseline symptom severity [21].
Next, the role of changes in PVR over time as a
predictor of future LUTS/BPH-related events became
clear from the placebo arm as well as from the
treatment arms of the MTOPS study. Indeed,
patients who did not develop AUR during the
follow-up had a stable PVR throughout the study,
while those who subsequently developed AUR
displayed a steady increase in PVR [35].
Finally, symptom deterioration during treatment—and increasing bother during treatment, in
particular—were identified as dynamic variables
predicting LUTS/BPH progression in the ALFuzosin
ONcE daily (ALF-ONE) study, a large open-label
european urology supplements 7 (2008) 680–689
‘‘real-life’’ study assessing the efficacy and safety of
alfuzosin at 10 mg once daily in real-life practice.
Failure to respond to alfuzosin, defined as a
worsening of IPSS 4 or a bother score >3 at the
last available assessment under treatment, was
shown to be a powerful predictor of AUR and BPHrelated surgery in the short term (6 mo) [36] as well
as in the long term (3 yr) [37].
Based on these predictors of LUTS/BPH progression, nomograms can be developed. These models
use a mathematical algorithm to help physicians
predict a patient’s individual risk of disease progression [38]. Currently, the MTOPS Prostatic
Sample Analysis (MPSA) Consortium is trying to
identify and validate new molecular markers that
may identify risk of LUTS progression. Using
different approaches, a high stromal-to-epithelial
ratio in the prostatic transition zone, as well as 19
unique autoantigens, were shown to be associated
685
with BPH progression. Moreover, detailed studies of
various PSA isoforms revealed that incorporation
of baseline serum levels of BPH-A, a mature,
enzymatically inactive, uncomplexed form of PSA,
significantly enhances the accuracy of nomograms
in predicting AUR and BPH-related surgery [39].
Hence, it is clear that the baseline and dynamic
predictors of LUTS/BPH progression can help physicians to tailor treatment to a patient’s individual
risk profile of progression. Patients who are at low
risk of disease progression require only a fast and
continued symptom relief with minimal morbidity
associated with treatment. However, for patients at
higher risk of progression, symptom relief should be
combined with continuous treatment aimed at
delaying the progression of the disease and the
development of complications [40]. In this way,
the management of LUTS/BPH can become more
cost-effective.
Fig. 3 – Impact of lower urinary tract symptoms (LUTS) on the quality of life (QoL) of both patients and their partners: (a)
Comparison of impact on QoL of LUTS and different stages of prostate cancer (PCa) [42]. Total International Prostate
Symptom Score (IPSS) and total Functional Assessment of Cancer Therapy–General (FACT–G) score (QoL questionnaire) are
compared among a control population, patients with moderate or severe LUTS (IPSS score in parentheses), and patients in
different clinical stages of prostate cancer (T1–T2: organ-confined prostate cancer; T3–T4: metastatic prostate cancer).
Severe LUTS cause a similar decrease in the QoL as 80% advanced prostate cancer. (b) Impact of symptomatic LUTS/BPH
(benign prostatic hyperplasia) on QoL of patients’ partners. The percentage of partners affected by several QoL-related
issues is depicted (n = 90). QoL is considerably affected in partners of LUTS/BPH patients [44].
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Fig. 4 – Opinions of 382 urologists participating in a Web-based survey on the management of a patient with a first
presentation of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). The percentage of
respondents preferring a certain treatment option is depicted. The patient’s bother and quality of life (QoL) appear to be
important drivers in taking treatment decisions for LUTS/BPH.
3.2.2. Other modern drivers for taking individual treatment
decisions
Next to a patient’s current degree of symptom
severity and his risk of progression and future
complications, at least two additional factors also
influence a medical physician’s treatment decision;
that is, the patient’s quality of life (QoL) and existing
comorbidities.
Although LUTS/BPH is not associated with pain
and does not involve a threat to life, the disease has
a significant impact on the QoL of patients. Men with
LUTS, and especially nocturia and incomplete
bladder emptying, experience a higher degree of
bother and interference with daily activities and a
higher degree of worry and impact on psychological
well-being than men without symptoms [41,42].
Severe LUTS have an even greater impact on the QoL
than do chronic illnesses such as diabetes, hypertension, angina, and gout [43] and advanced prostate
cancer (Fig. 3a) [42]. Moreover, the QoL of both
patients and their partners decreases as the severity
of LUTS increases (Fig. 3b) [41,42,44]. Therefore, it is
not surprising that the fear of symptom deterioration and concomitant QoL worsening is the main
reason for patients to consult a physician [45].
Hence, it is clear that a patient’s QoL is one of the
most important aspects that should be taken into
account by clinicians when deciding upon LUTS/BPH
management, as illustrated by the outcomes of a
Web survey among urologists (Fig. 4).
Another factor influencing the management of
LUTS/BPH is the presence of comorbidities. Indeed,
as this condition is quite common in ageing men, it
often occurs concomitantly with other common
age-related disorders such as cardiovascular disease, hypertension, diabetes, metabolic syndrome,
and erectile dysfunction [46]. Therefore, treatment
decisions should also be guided by the existence of
these comorbidities, since side-effects of medications might exacerbate the comorbid conditions.
4.
Conclusions
From the above, it is clear that the management of
LUTS/BPH is more than just treating symptoms. Four
main drivers for taking individual treatment decisions can be discerned (Fig. 5).
Firstly, the treatment of choice depends on the
severity and type of LUTS, which are known to have
a multifactorial aetiology. Voiding symptoms are
believed to be caused by obstruction at the level of
european urology supplements 7 (2008) 680–689
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Fig. 5 – Overview of four main drivers for taking individual treatment decisions in the management of lower urinary tract
symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH).
the prostate, while many different mechanisms,
including detrusor overactivity and aberrant stimulation of receptors in the bladder or its innervating
structures, can contribute to the development of
storage symptoms. Therefore, treatment for LUTS/
BPH should focus not merely on the prostate, but
also on other organs that play a role in disease
pathogenesis such as the bladder.
Secondly, the progressive character of LUTS/BPH
is an important driver for taking treatment decisions. As progressive pathological changes in the
bladder become irreversible beyond a certain stage,
treatment should aim at preventing disease progression in an early disease phase. Only in this way,
bladder function can be maintained and the development of serious complications such as AUR can be
avoided.
Consequently, physicians should be able to
determine a patient’s individual risk of disease
progression before taking treatment decisions. Until
now, seven parameters have been described to be
predictors of LUTS/BPH progression at baseline; that
is, age, baseline severity of LUTS, prostate volume,
PSA levels, Qmax, PVR, and prostatic inflammation.
In addition, three dynamic variables; ie deterioration of LUTS over time, increase in PVR over time,
and symptom worsening and/or increasing bother
during treatment, have also been recognized as
predictors of future LUTS/BPH-related events. Moreover, an extensive search for new biomarkers of
disease progression is still going on and should
result in a more accurate prediction of a patient’s
risk and, therefore, in a more cost-effective management of the disease.
Thirdly, as the QoL of both patients and their
partners is severely affected by LUTS/BPH and
is inversely correlated with the severity of LUTS,
this parameter should be considered carefully
by clinicians when deciding upon LUTS/BPH
treatment.
Finally, the treatment of choice for LUTS/BPH will
also depend on the existence of comorbidities in the
patient, since side-effects of several medications
might negatively affect these concomitant disorders.
All four factors should be taken into account in
the current management of LUTS/BPH. After assessing the causes of the disease and the risk factors for
progression, a differentiation should be made
between patients at low or at high risk of disease
progression. Treatment of patients at low risk
should aim at relieving the symptoms and especially
at improving the QoL, thereby causing minimal
morbidity or exacerbation of comorbid conditions.
On the other hand, patients at higher risk of disease
progression require a combination of the previous
strategy with a continuous treatment that protects
the bladder and avoids the development of complications. This current approach is more cost-effective and better adapted to a patient’s individual
symptoms, risks, and needs than the classical
treatment approach focusing merely on symptom
relief.
Conflicts of interest
Mark Speakman received an honorarium for presenting the lecture at the EAU symposium on which
this paper was based.
Funding support
The publication of this review was supported by
Astellas Pharma Europe.
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european urology supplements 7 (2008) 680–689
Acknowledgements
The author is grateful to Ismar Healthcare NV for
their assistance in writing the manuscript.
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