International Journal of Impotence Research (2008) 20, S19S26

& 2008 Nature Publishing Group All rights reserved 0955-9930/08 $30.00
www.nature.com/ijir

REVIEW

The utility of serum prostatic-specific antigen in the management

of men with benign prostatic hyperplasia
CG Roehrborn
Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA

Several analyses have demonstrated a clinically useful relationship between serum prostate
specific antigen (PSA) and prostate volume in men with benign prostatic hyperplasia (BPH) and
lower urinary tract symptoms (LUTS). Both prostate volume and serum PSA predict certain aspects
of the natural history of LUTS and BPH, and men with higher PSA and larger glands in general have
a higher rate of progression measured by various parameters. Serum PSA also predicts the response
to certain types of medical therapy in men with LUTS and BPH and is thus useful in the evaluation
and management of these patients. Lastly, serum PSA does not loose its usefulness as a cancer
marker for prostate cancer even if certain medications reduce serum PSA values predictably
by 50%.
International Journal of Impotence Research (2008) 20, S19S26; doi:10.1038/ijir.2008.53

Introduction
Benign prostatic hyperplasia (BPH) is the most
common benign tumor in men with prevalence
estimates ranging from 50% for men in their 50s to
90% for men in their 90s.1 Although not all men
suffer from this condition, approximately 50%
of those developing histological hyperplasia
eventually will develop moderate-to-severe and
bothersome, storage and voiding symptoms collectively called the lower urinary tract symptoms
(LUTSs). Because of its extraordinarily high prevalence of this in general nonlethal disease as well
as in the aging of the population, health care
providers in primary care and in urology will see
themselves confronted with an ever-enlarging
number of men seeking consultation, advice and
treatment for LUTSs often associated with BPH.
This review article will focus on the utility of
serum prostate-specific antigen (PSA) in the management of men with LUTSs secondary to BPH. We
will review the relationship between prostate size or
volume and serum PSA, and subsequently the
importance of prostate volume and serum PSA in
predicting the natural history of the condition.
Furthermore, we will examine the role of PSA in

Correspondence: Dr CG Roehrborn, Department of Urology, UT Southwestern Medical Center, 5323 Harry Hines
Blvd., J8.148, Dallas, TX, USA.
E-mail: claus.roehrborn@utsouthwestern.edu

predicting response to medical therapy for LUTS

and BPH, and lastly, we will examine how PSA
changes under medical or surgical treatment for
BPH and the important role it plays in monitoring
men on treatment or after surgery.

The relationship between prostate

volume and serum PSA
As we shall discuss in a subsequent section of this
review, prostate volume and a proxy for prostate
volume, serum total PSA, are powerful predictors
both of the natural history of LUTS and BPH as well
as the response to certain medical therapies. Therefore, it is clear that a knowledge of these parameters
would be beneficial in the everyday management of
patients presenting to health care providers. Intuitively, it may appear easiest to use prostate volume
for such purposes. However, this undertaking has
some problems, most notably owing to the fact that
digital rectal examination is quite inaccurate in
estimating the correct prostate size when measured
by either transrectal ultrasound (TRUS) or other
imaging modalities such as computerized tomography or magnetic resonance imaging.
An analysis of the relationship between digital
rectal examination estimates and TRUS volumes
was conducted using four sources, in which either a
single nurse, a single urologist or multiple personnel
examined men and estimated the prostate size.2
Subsequent to it, an ultrasound was performed to

PSA and BPH management

CG Roehrborn
S20

determine the actual prostate size. Digital rectal

examination estimates and TRUS volumes were
significantly correlated with an r-value between
0.4 and 0.9, but prostate size was underestimated
by 2555% for men with a prostate volume of over
40 ml depending on the study, with greater variability for studies involving multiple examiners.
Of course, it might be possible to measure each
mans prostate size by either TRUS, CT scanning or
magnetic resonance imaging; however, the logistics
as well as the cost of such undertakings would be
prohibitive, and if it were to be performed only for
the purpose of assessing prostate size in an effort to
predict the natural history or response to medication
for BPH, this policy would likely not be economically sustainable.
It is, therefore, logical to search for proxy parameters that could be used instead of prostate
volume. One such parameter is the serum prostatespecific antigen. PSA is produced in the glandular
epithelial portion of the prostate and is the most
widely used prostate cancer screening marker ever
since its introduction in the early 1990s. PSA has
significant drawbacks as a screening test for prostate
cancer, most notably because there is no single cutpoint, which indicates the presence or absence of
prostate cancer. Rather, findings from the prostate
cancer prevention study suggest that the risk for
prostate cancer increases with increasing PSA value
and decreases with decreasing PSA, but it never
reaches zero risk3 (Figure 1). In the management of
men with prostate diseases, it is of great importance
to recognize that, in fact, the notion of a monolithic
cut-point for serum PSA of 4.0 ng ml
1 is no longer
valid. All providers should view serum PSA as a risk
continuum, and referrals or indications for TRUSguided biopsies should be based on the current
serum PSA, the PSA history and velocity over time,
and on patient-related factors, such as age, comorbidities and so on.
Serum PSA is not only widely used as a screening
and testing tool for prostate cancer, but it is also of
considerable help in the management of men with

LUTS and BPH. With increasing age, both prostate

volume and serum PSA increase. The former has
been recognized for a long time and can be observed
in longitudinal as well as cross-sectional studies,1
and the latter is well documented and has led to the
development of so-called age-specific reference
ranges for serum PSA.48
Considering that both prostate volume and serum
PSA increase with age, it seemed reasonable to
assume some relationship between serum PSA and
prostate volume as well. Analyses of a database of
over 4600 men with LUTS and BPH, but no cancer
demonstrated, in fact, that prostate volume and
serum PSA have an age-dependent log-linear relationship (that is, their logarithms are linearly
related, and the parameters of the relationship
depend on age). Older men tend to have a steeper
rate of increase in prostate volume with increasing
serum PSA9 (Figure 2). Perhaps a more practical
question might be what serum PSA predicts with
reasonable clinical certainty the presence of a
prostate greater than 30 ml (or cc or g; all are
interchangeable, as the specific gravity of prostate
tissue is barely greater than 1.0) or greater than
40 ml. To maintain a specificity of approximately
70%, thus accepting a 30% false-positive rate, the
following thresholds of serum PSA need to be
applied to yield a sensitivity between 60 and 70%
as an answer to this question (Table 1).
Although the graphical display can be used to
estimate prostate volume by serum PSA and age or
vice versa, these thresholds indicate the likelihood
of the prostate to be greater than 30 or 40 ml,
respectivelya parameter that is useful in clinical
practice. It should be noted that several independent
investigators verified the log-linear relationship between serum PSA and prostate volume in
different population and ethnic groups with similar
results.1014

75
60

70

0.40

Prostate volume (ml)

65

Risk

Risk of
prostate
cancer

0.20

Risk of
high-grade
disease

60
55

50

50

40

0.00
0

PSA (ng ml-1)

Figure 1 Estimated risk of prostate cancer and high-grade cancer

as a function of serum PSA levels in the PCPT trial.3 PCPT,
prostate cancer prevention; PSA, prostate-specific antigen.

International Journal of Impotence Research

30
1

Serum PSA

Figure 2 Log-linear relationship between serum PSA and

prostate volume.9 PSA, prostate-specific antigen.

PSA and BPH management

CG Roehrborn
Table 1 Prostate volume by serum prostate-specific antigen and
age
40 ml

5059 years
6069 years
7079 years

41.3
41.5
41.7

41.6
42.0
42.4

Summary
There is a strong and clinically useful relationship
between serum PSA and prostate volume, which
enables the clinicians to estimate prostate size in
men with LUTS and BPH, and also to identify men
with prostate above certain thresholds.

Serum PSA predicts the natural history

of LUTS and BPH
Longitudinal data from the Olmsted County Community Study of Urinary Symptoms in men suggest
that, on average, the prostate grow by 1.6% or
approximately 1 ml per year.15,16 In the 5-year
Medical Therapy of Prostatic Symptoms (MTOPS)
study, the growth rate in the placebo-treated patients
was shown to depend on baseline serum PSA.17 In
those men with a PSA from 0.0 to 0.8 ng ml
1, the
average yearly growth rate was in fact 1 ml, but in
those men with a PSA greater than 3.0 ng ml
1, it was
3 ml per year. A similar analysis of the placebo-treated
patients in the 4-year Proscar Long-term Efficacy and
Safety Study (PLESS) also suggested a growth rate
difference based on the baseline serum PSAin the
lowest tertile of PSA, the growth rate was 7.4%; in the
middle tertile, it was 16.2% and in the highest tertile
of PSA, it was 22 or 5.4% per year, more than three
times the amount seen in the community-dwelling
men in Olmsted county.
The serum PSA predicts not only the future growth
of the prostate, but also the changes in the symptoms,
bother, interference with daily activities and maximum urinary flow rate in the PLESS.18 Djavan et al.19
reported that the serum PSA was a highly significant
predictor of symptomatic progression in a cohort of
conservatively managed patients, with the mean PSA
being 2.2 in those with and 0.83 in those without
progression. Similarly, serum PSA as well as prostate
volume were found to be the predictors of symptom
progression in the placebo group in the MTOPS study
(Figure 3).20
Bruskewitz et al.21 reported on the placebo-treated
patients in the 4-year PLESS, and their analysis
suggests that with increasing PSA tertiles, there is a
linear deterioration of frequency of sexual activity,
sexual satisfaction and the perception of overall
general health (Figure 4). Although this may have
been a surprising finding at the time, it is now clear
that there is a relationship between LUTS severity

Rate per 100 PYR

30 ml

<1.4
1.4 to 3.9
PSA 4.0

Progression

>4-Pt rise

AUR

Figure 3 Risk of overall progression, symptomatic worsening

and acute urinary retention stratified by serum PSA tertiles over 5
years in the placebo-treated patients in the MTOPS study.20 PSA,
prostate-specific antigen.

Sexual activity

Sexual frequency

General health

0.30

Mean (s.e) change from baseline

Age group

S21

0.10

0.10

0.30
1

Tertiles
Figure 4 Mean change from baseline in sexual activity, sexual
frequency and general health perception in placebo-treated
patients over 4 years in the PLESS stratified by PSA tertiles (1:
PSA 0.01.3; 2: PSA 1.43.2 and 3: PSA 3.312 ng ml
1).21 PSA,
prostate-specific antigen.

and erectile dysfunction and a variety of sexual

health measures. It does, therefore, seem logical to
assume that men with larger glands and higher
serum PSA may have an accelerated deterioration of
their sexual health as well.
Perhaps best understood and most significant is
the relationship between baseline serum PSA and
the risk for outcomes from LUTS and BPH, namely
acute urinary retention (AUR) and LUTS- and BPHrelated surgery. The placebo cohort in the PLESS
trial showed a nearly linear increase in risk for
either AUR or surgery with increasing serum PSA
levels over 4 years (Figure 5).22 Similar observations
were made in the placebo group in the MTOPS
study (Figure 3),20 in the Phase III trial program with
dutasteride23,24 as well as in the Olmsted County
Study, where the risk for AUR and/or treatment for
LUTS and BPH in men with baseline 1.4 or greater
was significantly higher.25 It is natural that the risk
for initiation of treatment in previously untreated
International Journal of Impotence Research

PSA and BPH management

CG Roehrborn
S22
Cumulative incidence (%)

30

20

Either
Surgery

10

AUR

.0
>2
.5
>3
.0
>3
.5
>4
.0
>4
.5
>5
.0
>5
.5
>6
.0
>6
.5
>7
.0
>7
.5
>8
.0

.5

>2

.5

>1

.5

>1

>0

>0

.0

Figure 5 Linear increase in risk for AUR and/or surgery in men

treated for 4 years with placebo in the PLESS trial.22 AUR, acute
urinary retention.

men, and specifically the risk for surgery, behaves

similarly to the risk of AUR as many AUR episodes
result in surgical treatment.

Summary
When first counseling a patient with LUTS and
presumed BPH, the serum PSA at that time is a
powerful predictor of the natural historycurrent
prostate size, future prostate growth, symptom and
bother deterioration, sexual dysfunction, urinary
flow rate worsening, AUR and even surgery. In
general, the higher the serum PSA, the greater the
risk and the faster the progression, or, the more
accelerated the natural history.

Serum PSA and response to medical

therapy
Serum PSA is useful not only in estimating the
prostate size, but also in predicting the response to
medical management with a-blockers (alfuzosin,
doxazosin, tamsulosin and terazosin), and five areductase inhibitors (five ARIs; dutasteride and
finasteride). Although in the early 1990s, both classes
of drugs were used interchangeably for the treatment
of men with LUTS and BPH, a more sophisticated
approach has resulted from a better understanding of
the mechanisms of action and the response to
different treatments in men with different baseline
parameters. What are these parameters? It has been
shown in many publications that the response to
a-blockers and 5-ARIs is similarly independent of the
patients age and even symptom severity at the
beginning of treatment,26,27 although the adverse
events reported with different a-blockers may vary
with age.28,29 Breaking down the LUTS into irritative/
storage vs obstructive/voiding symptoms may help to
some degree in distinguishing responses to 5-ARIs but
not necessarily to a-blockers, which reduce all
International Journal of Impotence Research

symptoms to an equal degree.30,31 Urinary flow rate

parameters and postvoid residual urine amount may
be of some additional help; however, they are, in
general, not available to the general practitioner at the
time of consultation.
More successful are the attempts to predict the
response to different therapies by baseline prostate
volume and baseline serum PSA values. Serum PSA
is readily available to all health care providers,
while prostate size is not. Since both are are related
as discussed before, we shall consider them interchangeably.
The general categories of response that we would
like to consider are:
(1) Changes in prostate volume over time.
(2) Changes in LUTS severity over time (also
representing the likely changes in bother,
interference with activities and quality of life
impairment).
(3) Likelihood of progression to AUR or surgery.

Ad 1
It is quite clear from large datasets that treatment
with a-blockers does not change prostate volume
over the short-to-intermediate term,32,33 and neither
does it prevent the long-term volume increases
commensurate with the natural history of the
condition as measured by placebo control groups.
In fact, in the MTOPS study, both groups of patients
treated with placebo and doxazosin experienced an
identical increase in volume, namely 18% over 4
years or approximately 4.5% per year.34 In contrast,
treatment with 5-ARIs induces, over a period of
612 months, on average, a 25% reduction in
prostate size, which is independent of the baseline
prostate size, baseline serum PSA or any other tested
parameter. In addition, as long as patients stay on
such medications, there seems to be no attenuation
of the effect, that is, the prostate gland does not seem
to change in size significantly over even longer time
periods of follow-up.23,35
Ad 2
An early meta-analysis of all terazosin trials suggested that it was effective and superior to placebo
in reducing symptoms and increasing the peak
urinary flow rate. The effect of terazosin on the
peak urinary flow rate was apparent in studies as
short as 8 weeks. Most importantly, the effect of
terazosin on the symptoms and peak urinary flow
rate was independent of the baseline prostate size
for the range of prostate volumes reported.36 In fact,
the longest controlled trials with a-blockers in the
5-year MTOPS and the 2-year Alfuzosin Long-term
Efficacy and Safety Study (ALTESS) studies suggested a sustained improvement in symptoms over

PSA and BPH management

CG Roehrborn
Log-rank test P=0.0013

Placebo

Alfuzosin
0.10

0.00
0

90

180

270

360

450

540

630

720

Time (days)

S23

20

30%

Cumulative incidence (%)

Percent with the event

0.20

Figure 6 The a-blocker is superior to placebo in preventing longterm symptomatic worsening or progression of LUTS defined
by a worsening in the symptom score by 4 points or greater.37
LUTS, lower urinary tract symptoms.

Placebo
Dox
Fin
Comb
10

0
<1.4

1.4 3.9
Baseline serum PSA (ng ml-1)

4.0

Figure 7 Cumulative incidence of symptomatic worsening by

X4 points in MTOPS for all four treatment groups stratified by
serum PSA.17 PSA, prostate-specific antigen.

Ad 3
There is now evidence from several studies to
suggest that a-blockers are less effective in preventing episodes of AUR and ineffective in preventing
surgical interventions over time, and this effect is
most likely because of the ongoing growth of the
prostate, which in turn is directly related to the risk
of AUR and surgery. The evidence comes from the
MTOPS and ALTESS studies,37,40 and Figure 8
demonstrates that the a-blocker treatment is effective in regard to AUR in men with serum PSA
o4.0 ng ml
1, but not in men with higher values,
whereas the 5-ARIs are effective across the entire

6
Placebo
Dox

Cumulative incidence (%)

time.17,37 In both the MTOPS and the ALTESS

studies, a-blocker therapy was superior to placebo
in terms of prevention of symptomatic progressi
on defined as an increase of X4 points on the
international prostate symptom score or International Prostate Symptom Score (IPSS) (Figure 6).
The symptomatic response to 5-ARI treatment,
however, is dependent on the baseline serum PSA/
prostate volume as was shown in two meta-analyses
summarizing data from all 1-year finasteride studies
available at the time.38,39 In general, the larger the
prostate gland and the higher the serum PSA, the
greater is the benefit of the 5-ARI over placebo,
which is a measure of therapeutic efficacy. Symptomatic improvements once achieved are also sustained over long periods of time.23,35
MTOPS allows a stratified analysis of the prevention of symptomatic worsening by treatment group
and serum PSA. With increasing serum PSA,
progression was increasingly more common in the
placebo group, the a-blocker reduced the risk
equally well in all PSA stratification, 5-ARI treatment was moderately effective in the intermediate
group and more effective compared with a-blocker
in the higher PSA groups, and the combination
therapy achieved the best reduction, particularly in
patients with the highest serum PSA (Figure 7).

Fin
Comb

<1.4

1.4 3.9
4.0
Baseline serum PSA (ng ml-1)

Figure 8 Cumulative incidence of progression to AUR in

MTOPS for all four treatment groups stratified by serum PSA.17
AUR, acute urinary retention; PSA, prostate-specific antigen.

range of serum PSA values. As the risk for AUR and/

or surgery increases with increasing serum PSA
values, the higher the PSA, the greater is the benefit
from 5-ARI treatment, as the risk reduction is 50%
independent of baseline risk (that is, a patient with a
10% baseline risk would experience a reduction
from 10 to 5%, and a patient with a 4% baseline risk,
a reduction from 4 to 2%, which would be less
cost-effective).24,41,42
Summary
Serum PSA is an excellent tool to determine how to
treat a patient with LUTS and BPH. In men with
PSA values of o1.5 ng ml
1, treatment with an
a-blocker is sufficient for symptomatic relief, and
as the risk of progression to AUR/surgery is low,
treatment with additional 5-ARIs is not necessary. In
men with a serum PSA of 41.5 ng ml
1, however,
a-blockers provide only symptomatic relief and
prevent symptom progression. In these patients,
International Journal of Impotence Research

PSA and BPH management

CG Roehrborn
S24

the risk of AUR or surgery increases, however,

and thus treatment with 5-ARI in addition to the
a-blocker is recommended.

Utility of serum PSA under medical

treatment for LUTS and BPH
Treatment with a-blockers neither affects the serum
PSA nor the PSA velocity or change over time.43
Thus, the utility of serum PSA is maintained
unaltered even during and after the long-term
therapy with this class of drugs.
5-ARIs predictably and reliably reduce serum PSA
and serum-free PSA on average by 50% after about
36 months of therapya fact that has been
confirmed in many randomized studies with both
finasteride and dutasteride.17,33,4446 However, individual results may vary greatly and the range of
the observed PSA changes is tremendous.47 This
leaves the practicing physicians with the following
concerns:
(1) What to do if the PSA level does not decrease by
at least 50% after 36 months (assuming that a
greater than 50% would indicate effective treatment with no increased risk for cancer).
(2) How to interpret the new nadir PSA level.
(3) How to interpret the changes from the new PSA
nadir level.
Ad1
If a patient does not have the expected decrease in
serum PSA, this may be because of either noncompliance with the drug or because of factors such as
concomitant inflammation in the prostate, manipulation of the prostate, or the presence of prostate
cancer. Referral and/or biopsy of the prostate may be
indicated.
Ad 2
In the past, the uniform recommendation had been to
multiply the new baseline nadir PSA value  2 and to
use the usual cut-points for referral and/or TRUSguided biopsy of the prostate. Sensitivity and specificity analysis have demonstrated that in this setting,
the serum PSA may maintain at least equal, if not
better, sensitivity/specificity when using such logic.48
Ad 3
Given the uncertainty over fixed cut-points to
recommend referral and/or TRUS biopsy, another
approach is to monitor the serum PSA nadir value
for changes in a positive direction, that is, an
increase.4951 An increase from stable nadir by 0.3
or 0.5 should trigger a check regarding the patients
compliance and perhaps a verification. If consistent,
however, it should trigger a referral/TRUS biopsy to
rule out cancer.
International Journal of Impotence Research

Summary
Under treatment with a-blocker, PSA may be used as
in a nontreated patient. Under treatment with 5-ARI,
a 50% reduction of serum PSA on average is
expected. Less than a 50% decrease, a value above
thresholds for referral/TRUS biopsy after multiplying the nadir value  2, or an increase from nadir
in a fully treatment-compliant patient should trigger
further action, such as referral, for a TRUS biopsy.

Disclosure
Claus G Roehrborn has received consulting fees and
lecture fees from GSK, Eli Lilly, Spectrum Pharmaceuticals, Aeterna Zentaris, Pfizer and AMS.

References
1 Roehrborn C, McConnell J. Etiology, pathophysiology, epidemiology and natural history of benign prostatic hyperplasia. In:
Walsh P, Retik A, Vaughan E, Wein A (eds). Campbells Urology,
8th edn. Saunders: Philadelphia, 2002, pp 12971336.
2 Roehrborn CG, Girman CJ, Rhodes T, Hanson KA, Collins GN,
Sech SM et al. Correlation between prostate size estimated by
digital rectal examination and measured by transrectal ultrasound. Urology 1997; 49: 548557.
3 Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS,
Parnes HL et al. Prevalence of prostate cancer among men with
a prostate-specific antigen level oor 4.0 ng per milliliter.
N Engl J Med 2004; 350: 22392246.
4 Bosch JL, Tilling K, Bohnen AM, Donovan JL. Establishing
normal reference ranges for PSA change with age in a
population-based study: the Krimpen study. Prostate 2006;
66: 335343.
5 Powell IJ, Banerjee M, Novallo M, Sakr W, Grignon D, Wood
DP et al. Should the age specific prostate specific antigen
cutoff for prostate biopsy be higher for black than for white
men older than 50 years? J Urol 2000; 163: 146148;
discussion 148149.
6 DeAntoni EP. Age-specific reference ranges for PSA in the
detection of prostate cancer. Oncology (Williston Park) 1997;
11: 475482, 485; discussion 485476, 489.
7 DeAntoni EP, Crawford ED, Oesterling JE, Ross CA, Berger ER,
McLeod DG et al. Age- and race-specific reference ranges for
prostate-specific antigen from a large community-based study.
Urology 1996; 48: 234239.
8 Oesterling JE, Jacobsen SJ, Chute CG, Guess HA, Girman CJ,
Panser LA et al. Serum prostate-specific antigen in a
community-based population of healthy men. Establishment
of age-specific reference ranges. JAMA 1993; 270: 860864.
9 Roehrborn CG, Boyle P, Gould AL, Waldstreicher J. Serum prostatespecific antigen as a predictor of prostate volume in men with
benign prostatic hyperplasia. Urology 1999; 53: 581589.
10 Hedelin H, Johansson N, Stroberg P. Relationship between
benign prostatic hyperplasia and lower urinary tract symptoms and correlation between prostate volume and serum
prostate-specific antigen in clinical routine. Scand J Urol
Nephrol 2005; 39: 154159.
11 Hochberg DA, Armenakas NA, Fracchia JA. Relationship of
prostate-specific antigen and prostate volume in patients with
biopsy proven benign prostatic hyperplasia. Prostate 2000; 45:
315319.
12 Hammerer PG, McNeal JE, Stamey TA. Correlation between
serum prostate specific antigen levels and the volume of the
individual glandular zones of the human prostate. J Urol 1995;
153: 111114.

PSA and BPH management

CG Roehrborn
13 Yu HJ, Chiang GJ, Chiu TY, Lai MK. Relationship between
serum prostate specific antigen concentration and prostate
volume. J Formos Med Assoc 1995; 94: 666670.
14 Bosch JL, Hop WC, Bangma CH, Kirkels WJ, Schroder FH.
Prostate specific antigen in a community-based sample of men
without prostate cancer: correlations with prostate volume,
age, body mass index, and symptoms of prostatism. Prostate
1995; 27: 241249.
15 Rhodes T, Girman CJ, Jacobsen SJ, Roberts RO, Guess HA,
Lieber MM. Longitudinal prostate growth rates during 5 years
in randomly selected community men 4079 years old. J Urol
1999; 161: 11741179.
16 Jacobsen SJ, Jacobson DJ, Rohe DE, Girman CJ, Roberts RO,
Lieber MM. Frequency of sexual activity and prostatic health:
fact or fairy tale? Urology 2003; 61: 348353.
17 McConnell J, Roehrborn C, Bautista O, Andriole Jr GL,
Dixon C, Kusek J et al. The long-term effects of doxazosin,
finasteride and the combination on the clinical progression of
benign prostatic hyperplasia. NEJM 2003; 349: 23852396.
18 Roehrborn CG, McConnell JD, Bonilla J, Rosenblatt S, Hudson
PB, Malek GH et al. Serum prostate specific antigen and
prostate volume predict long-term changes in symptom and
flow rate: results of a four-year randomized trial comparing
finasteride versus placebo. Urology 1999.
19 Djavan B, Fong YK, Harik M, Milani S, Reissigl A, Chaudry A
et al. Longitudinal study of men with mild symptoms of
bladder outlet obstruction treated with watchful waiting for
four years. Urology 2004; 64: 11441148.
20 Crawford ED, Wilson SS, McConnell JD, Slawin KM,
Lieber MC, Smith JA et al. Baseline factors as predictors of
clinical progression of benign prostatic hyperplasia in men
treated with placebo. J Urol 2006; 175: 14221426; discussion
14261427.
21 Bruskewitz R, Girman CJ, Fowler J, Rigby OF, Sullivan M,
Bracken RB et al. Effect of finasteride on bother and other
health-related quality of life aspects associated with
benign prostatic hyperplasia. PLESS Study Group. Proscar
Long-term Efficacy and Safety Study. Urology 1999; 54:
670678.
22 Roehrborn CG, McConnell JD, Lieber M, Kaplan S, Geller J,
Malek GH et al. Serum prostate-specific antigen concentration
is a powerful predictor of acute urinary retention and need for
surgery in men with clinical benign prostatic hyperplasia.
PLESS Study Group. Urology 1999; 53: 473480.
23 Roehrborn CG, Marks LS, Fenter T, Freedman S, Tuttle J,
Gittleman M et al. Efficacy and safety of dutasteride in the
four-year treatment of men with benign prostatic hyperplasia.
Urology 2004; 63: 709715.
24 Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G.
Efficacy and safety of a dual inhibitor of 5-alpha-reductase
types 1 and 2 (dutasteride) in men with benign prostatic
hyperplasia. Urology 2002; 60: 434441.
25 Jacobsen SJ, Jacobson DJ, Girman CJ, Roberts RO, Rhodes T,
Guess HA et al. Treatment for benign prostatic hyperplasia
among community dwelling men: the Olmsted County
study of urinary symptoms and health status. J Urol 1999;
162: 13011306.
26 Kaplan S, Garvin D, Gilhooly P, Koppel M, Labasky R, Milsten
R et al. Impact of baseline symptom severity on future risk of
benign prostatic hyperplasia-related outcomes and long-term
response to finasteride. The Pless Study Group. Urology 2000;
56: 610616.
27 Kaplan SA, Holtgrewe HL, Bruskewitz R, Saltzman B, Mobley
D, Narayan P et al. Comparison of the efficacy and safety of
finasteride in older versus younger men with benign prostatic
hyperplasia. Urology 2001; 57: 10731077.
28 Milani S, Djavan B. Lower urinary tract symptoms suggestive
of benign prostatic hyperplasia: latest update on
alpha-adrenoceptor antagonists. BJU Int 2005; 95(Suppl 4):
2936.
29 Roehrborn CG, Schwinn DA. Alpha1-adrenergic receptors and
their inhibitors in lower urinary tract symptoms and benign
prostatic hyperplasia. J Urol 2004; 171: 10291035.

30 Roehrborn CG, McConnell JD, Saltzman B, Bergner D,

Gray T, Narayan P et al. Storage (irritative) and voiding
(obstructive) symptoms as predictors of benign prostatic
hyperplasia progression and related outcomes. Eur Urol
2002; 42: 16.
31 Roehrborn CG, Van Kerrebroeck P, Nordling J. Safety and
efficacy of alfuzosin 10 mg once-daily in the treatment of
lower urinary tract symptoms and clinical benign prostatic
hyperplasia: a pooled analysis of three double-blind, placebocontrolled studies. BJU Int 2003; 92: 257261.
32 Roehrborn CG. Three months treatment with the alpha1blocker alfuzosin does not affect total or transition zone
volume of the prostate. Prostate Cancer Prostatic dis 2006; 9:
121125.
33 Lepor H, Williford WO, Barry MJ, Brawer MK, Dixon CM,
Gormley G et al. The efficacy of terazosin, finasteride, or both
in benign prostatic hyperplasia. Veterans Affairs Cooperative
Studies Benign Prostatic Hyperplasia Study Group. N Engl J
Med 1996; 335: 533539.
34 Roehrborn CG, McConnell JDM et al. Baseline prostate volume
and serum PSA predict rate of prostate growth: analysis from
the MTOPS data. J Urol 2003; 169(Suppl 4): 364.
35 Lowe FC, McConnell JD, Hudson PB, Romas NA, Boake R,
Lieber M et al. Long-term 6-year experience with finasteride in
patients with benign prostatic hyperplasia. Urology 2003; 61:
791796.
36 Boyle P, Robertson C, Manski R, Padley RJ, Roehrborn CG. Metaanalysis of randomized trials of terazosin in the treatment of
benign prostatic hyperplasia. Urology 2001; 58: 717722.
37 Roehrborn CG. Alfuzosin 10 mg once daily prevents overall
clinical progression of benign prostatic hyperplasia but not
acute urinary retention: results of a 2-year placebo-controlled
study. BJU Int 2006; 97: 734741.
38 Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts
outcome of treatment of benign prostatic hyperplasia with
finasteride: meta-analysis of randomized clinical trials.
Urology 1996; 48: 398405.
39 Boyle P, Roehrborn C, Gould L. Baseline serum PSA levels
predict degree of symptom improvement following therapy of
BPH with finasteride. J Urol 1997; 157: 134A.
40 McConnell JD, Roehrborn CG, Bautista OM, Andriole Jr GL,
Dixon CM, Kusek JW et al. The long-term effect of doxazosin,
finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349:
23872398.
41 Boyle P, Roehrborn C, Harkaway R, Logie J, de la Rosette J,
Emberton M. 5-Alpha reductase inhibition provides
superior benefits to alpha blockade by preventing AUR and
BPH-related surgery. Eur Urol 2004; 45: 620626; discussion
626627.
42 Roehrborn C, Bruskewitz R, Nickel GC, Glickman S, Cox C,
Anderson R et al. Urinary retention in patients with BPH treated
with finasteride or placebo over four years: characterization of
patients and ultimate outcomes. The PLESS Study Group. Eur
Urol 2000; 37: 528536.
43 Roehrborn CG, Oesterling JE, Olson PJ, Padley RJ, Group HI.
Serial prostate-specific antigen measurements in men with
clinically benign prostatic hyperplasia during a 12-months
placebo-controlled study with terazosin. Urology 1997; 50:
556561.
44 Kirby RS, Roehrborn C, Boyle P, Bartsch G, Jardin A, Cary MM
et al. Efficacy and tolerability of doxazosin and finasteride,
alone or in combination, in treatment of symptomatic benign
prostatic hyperplasia: the Prospective European Doxazosin
and Combination Therapy (PREDICT) trial. Urology 2003; 61:
119126.
45 Roehrborn C, Andriole G, Boyle P, Hofner K. Effect of the dual 5
alpha reductase inhibitor dutasteride on endocrine parameters
and prostate volume. Eur Urol 2002; 1(Suppl 1): 107.
46 Gormley GJ, Stoner E, Bruskewitz RC, Imperato-McGinley J,
Walsh PC, McConnell JD et al. The effect of finasteride in men
with benign prostatic hyperplasia. The Finasteride Study
Group. N Engl J Med 1992; 327: 11851191.

S25

International Journal of Impotence Research

PSA and BPH management

CG Roehrborn
S26

47 Brawer MK, Lin DW, Williford WO, Jones K, Lepor H. Effect of

finasteride and/or terazosin on serum PSA: results of VA
Cooperative Study #359. Prostate 1999; 39: 234239.
48 Thompson IM, Chi C, Ankerst DP, Goodman PJ, Tangen CM,
Lippman SM et al. Effect of finasteride on the sensitivity of
PSA for detecting prostate cancer. J Natl Cancer Inst 2006; 98:
11281133.
49 Andriole GL, Roehrborn C, Schulman C, Slawin KM,
Somerville M, Rittmaster RS. Effect of dutasteride on
the detection of prostate cancer in men with benign

International Journal of Impotence Research

prostatic hyperplasia. Urology 2004; 64: 537541; discussion

542533.
50 Andriole GL, Marberger M, Roehrborn CG. Clinical usefulness of serum prostate specific antigen for the detection of
prostate cancer is preserved in men receiving the dual 5 alphareductase inhibitor dutasteride. J Urol 2006; 175: 16571662.
51 Marks LS, Andriole GL, Fitzpatrick JM, Schulman CC,
Roehrborn CG. The interpretation of serum prostate specific
antigen in men receiving 5alpha-reductase inhibitors: a review
and clinical recommendations. J Urol 2006; 176: 868874.