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eau-ebu update series 5 (2007) 16–25
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Chronic Prostatitis Syndrome: A Common, but Poorly
Understood Condition. Part II
Michele Pavone-Macaluso *
Chair of Urology, Paolo Giaccone Polyclinic Hospital, University of Palermo, via del Vespro 129, 90127, Palermo, Italy
Article info
Abstract
Keywords:
Chronic prostatitis
Treatment
Fluoroquinolones
Alpha-blockers
The Chronic Prostatitis Syndrome (CPS) is defined as a complex of
symptoms which may arise in the prostate itself or in neighbouring
organs and structures, including the pelvic floor, as implied in the recent
NIH classification and terminology: Chronic Prostatitis/Chronic Pelvic
Pain Syndrome (CP/CPPS).
It may have different aetiologies and physiopathologic mechanisms
making treatment difficult and often unrewarding. As infection can be
demonstrated in some cases and suspected in other ones, antibacterial
treatment is often adopted as first measure. Fluoroquinolones, to be
administered for at least 30 days, are presently the drugs of choice.
Trimethroprim is another accepted option. Additional treatments
include alpha-blockers, antiinflammatory agents and many other drugs
and various treatment modalities, from prostatic massage to hyperthermia. There are few randomized studies versus placebo and many of
them have insufficient statistical power. Further trials are needed.
# 2006 European Association of Urology and European Board of Urology.
Published by Elsevier B.V. All rights reserved.
* Tel. +39 091 655 2403; Fax: +39 091 655 2439.
E-mail address: [email protected]
1.
Introduction
In a previous review [1] attention has been devoted
to recent concepts and advances regarding the
elusive condition called ‘‘chronic prostatitis syndrome’’ (CPS). It has been emphasised that a
uniformly accepted definition is yet to be agreed
on, although the National Institutes of Health (NIH)
classification ‘‘chronic prostatitis/chronic pelvic
pain syndrome’’ (CP/CPPS) has focused our attention
on a few facts. (1) The condition is characterised
by symptoms, although they are not specific and
may be lacking completely in category IV CP/CPPS.
(2) There is no pathognomonic pathology. (3) The
symptoms may arise in the prostate itself but can
also find their origin in adjacent structures, including the pelvic floor. Pain was considered to be the
most typical manifestation but may be lacking in
cases where micturition disorders are prevalent.
This led to the conclusion that CPS is not a wellstructured disease with uniform features, making
definitions and epidemiologic studies difficult and
ambiguous. In particular, considerable debate still
exists regarding the causative role of gram-positive
bacteria, Chlamydia and Ureaplasma. If these bacteria
are accepted as causative agents, the percentage of
patients considered affected by bacterial prostatitis
would become much higher. A great impact on these
1871-2592/$ – see front matter # 2006 European Association of Urology and European Board of Urology.
Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eeus.2006.10.001
17
eau-ebu update series 5 (2007) 16–25
concepts is generated by the different diagnostic
work-ups adopted in various centres, which may
include or exclude sperm culture, sperm analysis,
and search for Chlamydia and Ureaplasma organisms
and bacterial products.
Table 1 – A list of proposed drugs for treatment of chronic
prostatitis syndrome
Treatment
Antibiotics
a-Blockers
2.
Treatment
The problems encountered in obtaining a satisfactory definition and classification of CPS, its obscure
pathophysiology, and the lack of agreement regarding an optimal diagnostic algorithm have produced
even more unsolved controversies with regard to
treatment.
An important question involves the need of
stratifying patients into the various classification
categories, assuming that they will require differential treatments. The need to better define outcomes and cures is of paramount importance, and
uniform guidelines for future clinical trials should
be adopted [2].
Many forms of therapy have been implemented,
with results that are often presented as encouraging, but unfortunately most reports are empirical
and based on very low number of patients, with
undefined populations and unvalidated outcome
measures. Very few are randomised, double-blinded
studies with a placebo control arm and an adequate
statistical power. The value of the vast majority of
these reports remains open to question. Despite
these limitations and the variety of possible remedies, the recommendations for treatment are more
or less similar in different countries: Italy [3], France
[4], Germany [5], Europe [6], and North America [7–9],
as shown in Table 1. In addition to drug therapy,
complementary measures have been proposed, as
shown in Table 2. Some of these measures, such as
pain medications, are prescribed with a palliative
purpose, selected on the basis of symptom severity
[10]; others are designed to interfere with aetiologic
or pathogenetic factors.
2.1.
Drugs
2.1.1.
Antibacterial agents
An important observation regarding drug therapy
for CPS is that penetration of many substances into
the prostate is limited by a blood barrier. It is
common knowledge that such barriers exist for the
brain, testis, and epididymis. Recent findings have
demonstrated a blood–prostate barrier in the rat
ventral prostate with characteristics similar to the
blood–testis barrier [11]. This has been shown for
radiolabelled dextran, urea, and water. The exis-
Anti-inflammatory agents
5a- reductase inhibitors
Plant extracts
Pain control measures
Antidepressants
Muscle relaxants
Antimuscarinics
Heparinoids + antihistamines
Allopurinol
Examples
Quinolones, trimethoprim,
macrolides
Tamsulosin, alfuzosin, doxazosin
Nimesulide, celecoxib
Finasteride, dutasteride
Quercetin, Serenoa repens, pollen
extracts
Trazodone, aspirin, paracetamol
Sertraline
Diazepam, baclofen
Tolterodine, trospium, solifenacin
Pentosan polysulphate + hydroxyzine
Zyloric
tence of such a barrier had been suspected for
several years but was mainly applied to poor
penetration of antibiotics from plasma into the
prostatic secretion. This was attributed to particular
pharmacokinetics of antibiotics, depending on
degree of ionisation, pK, protein binding, and lipid
solubility [12]. For this reason, the choice of the
antibacterial agent for the treatment of CPS
depended much more on the knowledge of its
pharmacokinetics than on in vitro sensitivity tests.
Clinical experience had shown that trimethoprim
has the most favourable pharmacokinetics, followed by the quinolones and some macrolides
and tetracyclines, whereas b-lactams and aminoglucosides show poor penetration in the prostatic
tissue. It is unknown to what an extent such
penetration restrictions apply also to drug categories other than antibiotics.
For these reasons, the pharmacokinetics of
various antibacterial agents have been thoroughly
investigated, by measuring their concentration in
prostatic fluid and in prostatic tissue in dogs and
in benign prostatic hyperplasia (BPH) specimens in
men. However, drug pharmacokinetics may vary
Table 2 – Complementary measures for treatment of
chronic prostatitis syndrome
Prostatic massage
Biofeedback
Thermotherapy
Myofascial trigger point release
Psychotherapy
Hot sitz baths
Acupuncture
Meditation
Diet
Surgery
Intraprostatic injection of antibiotics
Botulinum toxin injection
Electromagnetic therapy
High-frequency electrostimulation
18
eau-ebu update series 5 (2007) 16–25
considerably between dogs and humans because of
the different pH conditions.
Furthermore, the distribution of drugs between
adenomatous and normal human prostatic tissue
may not be identical. The results from these
experiments should therefore be interpreted with
caution. Concentration in seminal fluid in men may
provide useful information for this issue. There is
consensus among different authors that antibiotic
treatment of CPS should be prolonged, because,
according to several reports, the best cures have
been obtained using long-term treatment. Pfau [13]
reported on a limited number of cases treated with
cotrimoxazole in which none of the patients
responded to a short-term treatment of 10–30 d,
whereas 50% of patients were cured if treated for
4–8 mo. The optimal duration of treatment is still
unknown, but it seems logical to give preference to
oral rather than parenteral administration for such
prolonged treatment. Therefore, aztreonam, which
reaches relatively high concentrations in the
seminal fluid, is seldom used because of its
obligatory intramuscular administration [14]. It
has been suggested that a relatively shorter treatment (1–2 mo) can be envisaged for fluoroquinolones, whereas 3 mo is the standard duration of
treatment for trimethoprim-based therapy.
There is also consensus on the fact that, whenever Chlamydia, Ureaplasma, Gonococcus, or Candida
organisms or other sexually transmitted germs are
isolated from patients with CPS, whether or not they
are considered as the main aetiologic agent, antibiotic treatment should be given simultaneously
also to the sexual partners.
Before engaging ourselves in a revision of the
current knowledge about antibiotic treatment
of CPS, we should consider the following issues:
(1) indications for antibiotic treatment and (2) choice
of the drug.
2.1.1.1. Indications for antibiotic treatment. There is agreement on the indications for the use of antibacterial
agents in cases of acute and chronic bacterial
prostatitis. However, many clinicians still treat with
antibiotics, at least as the initial therapy, practically
all patients with CPS in the belief that an infections
aetiology may still be responsible for most cases,
despite our failure to demonstrate the presence of
the aetiologic factor. This may be due to several
factors, such as presence of antibacterial factors in
prostatic fluid or semen, blockade of prostatic ducts
by inflammatory oedema or fibrosis or calculi, lack
of elaborate investigations to detect particular
bacterial species, positivity of bacterial products,
isolation of bacteria in biopsy specimens, and
knowledge that some patients with CPS category III
do respond to treatment. This issue will be discussed
further.
2.1.1.2. Choice of the antibacterial drug. For common
germs, a combination of trimethoprim with a
sulphonamide, co-trimoxazole, or kelfiprim [15]
has been the treatment of choice for many years,
due to the high penetration of trimethoprim in
prostatic fluids. However, the sulpha moiety shows
little activity and may cause an allergic reaction and
trimethoprim alone is not commercially available in
several countries. In recent years, the fluoroquinolones have become the standard of care for the
treatment of bacterial prostatitis. Norfloxacin shows
limited penetration [16], ofloxacin has some activity
against chlamydiae [17], and ciprofloxacin and
levofloxacin have shown good pharmacokinetic
properties and a broad spectrum of activity.
Bundrick et al [18] have shown that levofloxacin
500 mg once daily is as effective as ciprofloxacin
500 mg twice daily. Levofloxacin may be preferred,
having the advantage of single daily administration.
For an extensive bibliography on this topic the
reader is referred to the reviews by Bjerklund
Johansen et al [6] and Nickel and Moon [19]. Not
all treated patients show a full response. Schaeffer
et al [20] showed that of 337 men treated with either
ciprofloxacin or levofloxacin for 28 d, those who
failed to show a reduction of prostate-specific
antigen (PSA) after treatment had a lower incidence
of bacteriologic cure (eradication rate was slightly
>60%). Similar results were obtained by Botto [21]
who described bacteriologic cure in 75% and 73% of
patients treated, respectively, with levofloxacin and
ciprofloxacin.
However, response rates are much lower in
pretreated patients. Alexander et al [22] described
that ciprofloxacin, even with the addition of the
a-blocker tamsulosin, did not reduce symptoms in
men with long-standing CPS, but treatment >6 wk
was not tested. Some workers have proposed direct
injection of antibiotics directly into the prostate [23].
After the original report by Baert et al [23], the most
recent advocates of this approach are Guercini et al
[24]. They use a cocktail of antibiotics and betamethasone, repeated at weekly intervals. They
claim satisfactory results, but we have never been
convinced that a uniform distribution of the drugs
can be obtained with this invasive manoeuvre and
agree with Nickel [25] that some results reported in
the literature are provocative but require further
evaluation. Nickel’s comments are that ‘‘many
prostatitis experts tried direct antibiotic injections
in a few patients with no significant clinical results.
eau-ebu update series 5 (2007) 16–25
This approach has never been thoroughly evaluated
in a well designed clinical trial.’’
If Chlamydia or Ureaplasma species are present,
different antibiotics should be used. Among quinolones, the greatest activity against chlamydiae is
shown by ofloxacin. Tetracyclines, such as minocycline or doxycycline, are active against both chlamydiae and mycoplasma. Among macrolides,
clarithromycin and azithromycin have also shown
good activity. Azithromycin is used in a single dose
in the treatment of acute urethritis caused by
chlamydiae, but the usual long-term regimen
should be recommended for the treatment of
chlamydiae-associated CPS. Smelov et al [26] have
shown that azithromycin and ofloxacin were the
most effective drugs in vitro, but recommend
ofloxacin as the primary drug in the treatment of
chlamydiae-infected patients with CPS.
2.1.2.
a-Blockers
Therapy with a-blockers has been reported by
several authors to improve the voiding symptoms
and the discomfort associated with CPS. An
improvement in uroflow is to be expected in
patients with reduced flow, but improvement of
other symptoms was also observed even in patients
who had a nonobstructed voiding pattern.
De la Rosette et al [27] used alfuzosin versus
placebo, whereas Neal and Moon [28] used terazosin.
Three fourths of the patients, belonging to NIH
categories IIIa and IIIb, showed a symptomatic
improvement if treated for 1 mo. Fifty percent of
responders remained asymptomatic after discontinuation of the treatment. Tamsulosin has been used
by other workers [29].
Barbalias [30] makes a plea for the combined use
of antibiotics and a-blockers, especially in patients
suffering from ‘‘painful male urethral syndrome,’’
which is roughly equivalent to prostatodynia. He
believes that a-blockers act primarily by abolishing
intraprostatic urethral reflux and urethral hypertonia secondary to increased adrenergic stimulation
[31].
2.1.3.
Anti-inflammatory agents and analgesics
Enzymatic anti-inflammatory agents, such as chymotrypsin, have been occasionally used, but most
reports deal with nonsteroidal drugs such as nimesulide [32] or the new cyclooxygenase 2 (COX-2)
inhibitors (rofecoxib and celecoxib). They act not only
with an anti-inflammatory mechanism but have
intrinsic analgesic properties and can be efficacious
in alleviating pain and discomfort even in patients
without a demonstrable inflammatory component.
Long-term administration is not encouraged because
19
of gastrointestinal and cardiovascular side-effects,
the latter being not exclusively produced by the COX2 inhibitors. If pain is severe, the common pain killers
(trazodone, paracetamol) may be of significant
benefit.
2.1.4.
5a-Reductase inhibitors and hormones
Finasteride has been submitted to randomised
studies versus placebo, but the first trial was
underpowered and the apparent benefit was equivocal [33]. Three clinical studies suggest potential
efficacy of finasteride in ameliorating symptoms
due to CPS [34]. A more recent placebo-controlled
multicentre study confirmed that finasteride may be
of some benefit (75% of patients of the finasteride
and 54% of the placebo group reported at least a mild
improvement), but the authors concluded that the
results do not justify recommending finasteride as
monotherapy in patients with CPS. No experience
with dutasteride has been hitherto reported, to our
knowledge.
Various hormones, including paradoxically either
androgens or oestrogens, have been used in the past
with conflicting results.
2.1.5.
Plant extracts
Pollen extracts (Cernilton, prostat/poltit) have been
claimed to have anti-inflammatory properties and
to offer symptomatic relief in patients with either
CPS or BPH [35,36].
Serenoa repens, also called saw palmetto, has been
extensively used for BPH, but there is only one
prospective study for CPS. Serenoa was less effective
than finasteride [37]. A bioflavonoid, quercetin,
produced a reduction of symptom score in 67% of
patients versus 20% in patients receiving placebo
[38].
2.1.6.
Antidepressants
A placebo-controlled trial [39] showed a trend in
favour of sertraline after 13 wk of treatment. Patients
treated with the antidepressant showed not only an
improvement in depression score but also a reduction of prostatic symptom severity. Unfortunately,
the number was not sufficient to achieve statistical
significance.
2.1.7.
Drugs used for treatment of interstitial cystitis
The similarities and the possible relationship
between CPS and interstitial cystitis (IC) in men
have already been discussed in a previous review [1].
It was then a logical step to try using in patients with
CPS category III the same treatments that can offer
relief of symptoms in IC. Pentosan polysulphate
(PPS) alone [40–43] or in combination with hydro-
20
eau-ebu update series 5 (2007) 16–25
xyzine hydrochloride (an antihistamine provided
with anxiolytic properties) have been tested in
recent years [42]. Pentosan polysulphate, a glycosaminoglycan, was used at the dose of 100 mg 3 times
daily for 6 mo in a first study [40], but the dose was
increased to 900 mg daily for 16 wk in a subsequent
randomised study versus placebo [41]. The PPS
group showed a significantly greater improvement
in quality-of-life domain score than the placebo
group, but some patients suffered from nausea and
diarrhoea. Even better results were obtained by the
addition of hydroxyzine hydrochloride (Atarax) to
PPS [42], but some patients had a relapse after an
excellent initial response and others complained of
sleepiness and dizziness, so that Atarax was
discontinued [43].
2.1.8. Other drugs
2.1.8.1. Administration. Gabapentin, colchicine, cyclos-
porine, thalidomide, cytokine inhibitors, antifungal
agents (ketoconazole), mepartricin [44], muscle
relaxants (diazepam, baclofen), cannabinoids, capsaicin, and antimuscarinic drugs have been used
with variable success. Allopurinol has been tested
on the grounds that penetration of uric acid in the
prostate and crystal formation may play a pathogenetic role in CPS [45]. Ingenuity or despair from
patients or clinicians have also led to attempts at
cure using an endless variety of ‘‘natural therapies’’
such as plant products, from Echinacea to flowers of
prickly pears (Opuntia ficus indica) or the so-called
homeopathic remedies.
for 20 d was quoted with favourable clinical response
in 75% of patients, whereas the remaining 25%
showed only moderate improvement of symptoms
[48].
2.2.
Physical and instrumental methods and surgery
2.2.1.
Massage
Repetitive prostatic massage is an old tool in treating
patients with CPS, but has been almost universally
abandoned in recent years at least as a primary
treatment. Then, via the Internet, the information
reached many frustrated patients that physicians in
Manila had a great success in treating CPS patients
with massage and antibiotics [4]. Many patients flew
from the United States to the Philippines, were
treated, and were re-evaluated on their return home
[49,50]. The conclusion was that this approach may
be promising but its ultimate value needs to be
confirmed. In a recent study from Egypt [51],
prostatic massage did not improve the response of
patients treated with antibiotics for CPS NIH
categories II and IIIa.
No controlled study allows the evaluation of the
effects of prostatic massage alone. The mechanism
whereby prostatic massage may help patients with
CPS is open to a number of interpretations; it could
assist in the drainage of material obstructing the
prostatic acini and may improve blood flow and
antibiotic delivery to the prostate. It may also trigger
a relaxation of pelvic muscle spasm. It deserves
further investigations.
2.1.8.2. Local administration. Apart from the intraprostatic injection of antibiotics, other attempts have
been made to reduce symptoms in CPS patients by
administering drugs by perisphincteric or intraprostatic injection.
2.2.2.
Botulinum toxin type A was used by perisphincteric injection in 11 patients by a group of workers
from the United States, Germany, and Japan [46].
They concluded that weakening of the urethral
sphincter is followed by pain relief, increase of
uroflow, and symptom improvement.
A different approach has been adopted by Korean
workers, who state that ‘‘many investigators have
found that chronic prostatitis is associated with a
drop in zinc content.’’ Accordingly, they injected
zinc into the prostate of normal rats, observed that
prostatic zinc level was maintained for at least 4 wk
without any toxicity, and suggested that this
method can be applied in the treatment of CPS [47].
Finally, intrarectal administration of tablets containing proteolytic enzymes (papain, trypsin),
hydrolysate of calf thymus, and plant extracts daily
2.2.3.
Hot sitz baths
This is another old-fashioned treatment, which is
still adopted and may be useful in relieving symptoms but has never been tested in a proper study.
Pelvic electromagnetic therapy
Satisfactory results were reported by Rowe et al [52].
The authors believe that the chronic pelvic pain
syndrome is due to muscular neural dysfunction of
the urinary tract rather than to infection or
inflammation. Therefore, they assume that interference with this dysfunction is the only logical way
to treat CPS and advise electromagnetic therapy for
this purpose. Sacral magnetic stimulation [53] and
high-frequency electrostimulation have also been
used following the same rationale.
2.2.4.
Microwave thermotherapy
Hyperthermia and thermotherapy have been used
for treatment of CPS since 1991 [54,55]. More
recently [56], transurethral microwave thermotherapy (TUMT) with urethral cooling was evaluated in
eau-ebu update series 5 (2007) 16–25
39 patients with ‘‘intractable chronic prostatitis.’’
Improvement of total symptom score from baseline
values was 51% and improvement in pain score was
60%. Side-effects were minimal and transient and
the treatment ‘‘appears to be promising.’’
2.2.5.
Acupuncture
Acupuncture has been claimed to ameliorate symptoms of CPS with satisfactory results [57].
2.2.6.
Other manipulative methods
Caudal anaesthetic block; myofascial trigger point
release; pressure on soft tissue, joints, and bones;
and chiropractic and osteopathic manipulations
have been purported as useful methods in treating
CPS.
2.2.7.
Surgery
Surgery is frequently advocated by frustrated
patients who hope that some form of surgical
intervention may give them a hope of final resolution and permanent cure. Even total prostatectomy
has been proposed in extreme cases, but the
inherent risks of impotence and incontinence seem
out of proportion for what is, after all, a benign
disease.
Less invasive procedures, such as limited or
extensive transurethral resection of the prostate,
aimed at removing the affected parts of the prostate,
specially those containing calculi [58], are advocated
by some [59], but there is little evidence to confirm
its durable efficacy. Furthermore, there is the risk of
introducing an additional inflammatory condition
and to make things become worse.
2.2.8.
Alternative therapies
A list of non-conventional therapies can be added to
various attempts to treat refractory CPS, including
biofeedback, traditional Chinese medicine, Ayurveda, meditations, prayer, ‘‘creative therapy,’’
including art, music, and dance.
2.2.9.
Psychological support and psychotherapy
These methods appear to be of primary importance
in the frequent case of patients who develop severe
anxiety and depression. In our experience, many
patients do not accept being interviewed and treated
by a psychologist or a psychiatrist. Some patients
even resent such a suggestion because as they do
not want to be considered neurotic or hysterical, but
they want to be treated for a real organic disease.
Those who accept do usually experience a real
benefit, but there is a lack of exhaustive reports on
the long-term results of psychological treatment for
these patients. A careful analysis of the occurrence
21
of mental distress related to CPS was carried out in
Finland [60] in a population-based survey of 2500
men. The authors reported that 17% of patients with
CPS presented fear of undetected cancer. Fear of
having a sexually transmitted disease and suicidal
thinking were even more common and 43% had
decreased libido, erectile dysfunction, or marital
problems. They concluded that ‘‘urologists and
general practitioners should consider that a consultation with a psychiatrist may be appropriate for
selected men with prostatitis,’’ but they give no
information about frequency and results of such
consultations.
In any case, it is fundamental for every clinician
who takes responsibility for treating these patients
to offer them a warm sympathetic approach and to
be ready to listen to them with patience and
dedication.
2.2.10.
Changes in lifestyle
Patients are usually advised to avoid beer, strong
alcoholics, pepper, and paprika and to have regular
sexual activity, refraining from abstention, excess,
and coitus interruptus. They are also encouraged to
foster physical exercise; to avoid prolonged sitting,
bicycle riding, and perineal microtraumas; and to
correct any abnormalities in intestinal function.
Such measures are frequently of some help. Stress
reduction is often recommended but is seldom
applicable.
2.2.11.
Combination therapy
Antibiotics are frequently administered together
with a-blockers or anti-inflammatory agents. Workers from Taiwan [61] have described their experience with a combination regimen including
ciprofloxacin, doxazosin, allopurinol, biofeedback,
and perineal massage. They claim that in NIH
category IIIa patients they obtained a very high
response rate.
3.
Concluding remarks on therapy of CPS
As pointed out by Nickel et al [62], many forms of
therapy have been used for bacterial and nonbacterial CPS and most of them have been credited with
some degree of success, but the overwhelming
number of these attempts were based on relatively
few and nonhomogeneous patients, often without
controls and with variable response criteria. The
placebo effect in prostatic disease cannot be
neglected, especially in a condition such as CPS in
which psychogenic factors play an important role.
Even for BPH, a significant improvement not only in
22
eau-ebu update series 5 (2007) 16–25
symptoms but also in objective parameters, including uroflow and postvoid residual urine, has been
observed in placebo-treated controls in trials
devoted to test the efficacy of finasteride or
a-blockers. The same caveat should be considered
for the evaluation of the effects of invasive treatment, in view of the placebo-like action of sham
operations. In fact, some of the published studies on
treatment of CPS are randomised and placebocontrolled [18,29,33,36,38,41,44,45,52,55] but, as
Nickel (author of some of such publications)
honestly admits [62] practically all of them are
underpowered and cannot be attributed the rank of
grade I evidence.
In conclusion, our choice of treatment cannot rely
on the principles of ‘‘evidence-based medicine’’ and
no universally applicable algorithm or guidelines
can be put forward.
The most cogent question is the following: Can all
patients with demonstrated or suspected CPS be
treated in the same way, starting with a 30-d course
of quinolones and shifting to a-blockers or antiinflammatory agents in case of failure or recurrence? This may represent a reasonable solution if
we believe that many cases targeted as nonbacterial
(adopting the conventional diagnostic criteria) do
harbour occult microorganisms. This approach
would save us a considerable amount of time and
money. Alexander [22], a well-known and respected
authority in this field, reaches the conclusion that
‘‘data from recent studies do not support the tenets
upon which the diagnosis and treatment of prostatitis have been based for the past three decades. The
four-glass test should be abandoned and it is time
for the urologist to accept the findings of careful
clinical trials rather than outdated untested dogma
when deciding how best to help their patients.’’ This
is specially true for patients with long-standing CPS
in whom repeated courses of antimicrobial drugs
appear to be useless and the treatment should be
directed towards palliation of symptoms, psychological support, and encouragement. For each
patients the clinician’s judgement and skill may
select one of the different therapeutic weapons
resulting from the current literature, starting with
the less invasive with the most favourable cost–
benefit criteria. We do not favour the first-line
simultaneous use of various drugs that leads to
the impossibility of finding out which is effective,
if any.
We would agree with Alexander’s suggestion that
we should humbly start again from the very
beginning and implement multicentre welldesigned comparative trials with an adequate
statistical power. In the meantime, we still believe
that we should not abandon our current diagnostic
work-up and try to sort out the cases in which an
aetiologic agent can be identified. The percentage of
cases falling in the category of chronic bacterial
prostatitis can vary according to the more or less
extensive diagnostic work-up. Chronic bacterial
prostatitis remains an ‘‘evolving clinical enigma’’
[19], but it seems logical to continue to treat these
patients with antimicrobial agents, although bacteriologic cures in patients with bacterial prostatitis
treated with various quinolones were, on average,
only between 60% and 70%. Whether or not the
addition of a-blockers or prostatic massage will
improve the results cannot be substantiated with
certainty at the present time.
The treatment of prostalgia, chronic pelvic pain
syndrome, or NIH categories IIIa and IIIb rests on
even more empirical grounds. According to Nickel
[63], some clinical benefits can be obtained with
antibacterial therapy in patients with antibioticnaive early-onset CPS. The a-blockers can be tried as
first-line therapy in patients with moderately severe
symptoms never treated before with drugs. Antiinflammatory therapy is not recommended as a
primary treatment, but it may be helpful in an
adjunctive role in a multimodal therapeutic regimen. Similarly, finasteride, herbs, pollen, neuromodulation, immunotherapy, cognitive behavioural
intervention, and a few other measures still under
study may help in selected cases and improve
quality of life. Do we need a multidisciplinary
approach to diagnosis and treatment? It may well
be the best management strategy for our future
developments. The sympathetic approach to the
patient and an optimal doctor–patient relationship
remains of paramount importance. We agree with
Nickel’s concluding remarks that ‘‘the management
of chronic prostatitis will always be an art but it
is rapidly becoming more as a science as well.’’
At least, we hope so.
References
[1] Pavone-Macaluso M. Chronic prostatitis syndrome:
a common, but poorly understood condition. Part I.
EAU–EBU Update Series 2007;5:1–15.
[2] Propert KJ, Alexander RB, Nickel CJ, et al., for the Chronic
Prostatitis Collaborative Research Network. Design of a
multicenter randomized clinical trial for chronic prostatitis/chronic pelvic pain syndrome. Urology 2002;59:870–6.
[3] Rizzo M, Marchetti F, Travaglino F. Prevalence, diagnosis
and treatment of prostatitis in Italy: a prospective urology
outpatient practice study. BJU Int 2003;92:955–9.
[4] Valeri A, Joulin V, Fournier G. Prostatites. Encycl Med Chir
(Elsevier, Paris). Néphrol Urol 1998;18-520-A-10:1–11.
eau-ebu update series 5 (2007) 16–25
[5] Weidner W, Brunner H, Krause W, Rothauge CF. Therapy
of prostatitis. München, Germany: W. Zuckschwerdt
Verlag; 1985.
[6] Bjerklund Johansen TE, Grüneberg RN, Guibert J, et al. The
role of antibiotics in the treatment of chronic prostatitis: a
consensus statement. Eur Urol 1998;34:457–66.
[7] Nickel J. Prostatitis: lessons from the 20th century. BJU Int
2000;85:179–83.
[8] Nickel J, Nigro M, Valiquette L, et al. Diagnosis and
treatment of prostatitis in Canada. Urology 1998;52:797–
802.
[9] Krieger JN, Egan KJ. Comprehensive evaluation and treatment of 75 men referred to chronic prostatitis clinic.
Urology 1991;38:11–9.
[10] Clemens JQ, Brown SO, Kozlott L, Calhoun EA. Predictors
of symptom severity in patients with chronic prostatitis
and interstitial cystitis. J Urol 2006;175:963–7.
[11] Fulmer BR, Turner T. A blood–prostate barrier restricts
cell and molecular movement across the rat ventral prostate epithelium. J Urol 2002;163:1591–4.
[12] Madsen PO, Dorflinger T, Larsen EH, Gasser T. Pharmacokinetics of antibacterial agents used for treatment of
bacterial prostatitis. In: Weidner W, Brunner H, Krause W,
Rothauge CF, editors. Therapy of prostatitis. München,
Germany: W. Zuckschwerdt Verlag; 1985. p. 17–20.
[13] Pfau A. Prostatitis. Reflections and advice. Curr Opin Urol
1994;4:45–9.
[14] Ammatuna P, Romano C, Falletta C, et al. Concentrazioni
di aztreonam nel plasma, nell’urina e nel liquido seminale
di soggetti affetti da prostatite cronica. Arch Ital Urol
1992;44:177–81.
[15] Pisani E, Pavone-Macaluso M, Rocco F, et al. Kelfiprim, a
new sulpha-trimethoprim combination, versus cotrimoxazole in the treatment of urinary tract infections: a multicentre, double-blind trial. Urol Res 1982;10:41–4.
[16] Pavone-Macaluso M, Di Trapani D, Passerella E, Miglioli
PA, Berti T. Norfloxacin penetration into seminal fluid and
prostatic adenoma. Proceedings of the 4th meeting of the
Mediterranean Society of Chemotherapy, Rhodes, October
1984.
[17] Naber KG, Kinzig M, Sorgel F, Weigel D. Penetration of
ofloxacin into prostatic fluid, ejaculate and seminal fluid.
Infection 1993;21:98–100.
[18] Bundrick W, Heron SP, Ray P, et al. Levofloxacin versus
ciprofloxacin in the treatment of chronic bacterial prostatitis. A randomized double-blind multicenter study.
Urology 2003;62:537–41.
[19] Nickel JC, Moon T. Chronic bacterial prostatitis: an evolving clinical enigma. Urology 2005;66:2–8.
[20] Schaeffer AJ, Wu SC, Tennenberg AM, Kahn JB. Treatment
of chronic bacterial prostatitis with levofloxacin
and ciprofloxacin lowers serum prostate specific antigen.
J Urol 2005;174:161–4.
[21] Botto H. Place de la lévofloxacine dans la prise en charge
des infections prostatiques. Méd Mal Infect 2003;33(Suppl.
B):62–3.
[22] Alexander RB, Propert KJ, Schaeffer AJ, et al. Ciprofloxacin
or tamsulosin in men with chronic prostatitis/chronic
pelvic pain syndrome. Ann Intern Med 2004;141:581–9.
23
[23] Baert L, Mattelaer J, De Nollin P. Treatment of chronic
bacterial prostatitis by local injection of antibiotics into
prostate. J Urol 1983;11:370–5.
[24] Guercini F, Pajoncini C, Bard R, et al. Echoguided drug
infiltration in chronic prostatitis: results of a multicentre
study. Arch Ital Urol Androl 2005;77:87–92.
[25] Nickel JC. Antibiotics for bacterial prostatitis. J Urol
2000;163:1407.
[26] Smelov V, Perekalina T, Gorelov A, Smelova N, Artemenko
N, Norman L. In vitro activity of fluoroquinolones, azithromycin and doxycycline against Chlamydia trachomatis
cultured from men with chronic lower urinary tract
symptoms. Eur Urol 2004;46:647–50.
[27] De la Rosette JJ, Karthaus HF, van Kerrebroek PE, Boel T,
Debruyne FM. Research in prostatitis syndrome: the use
of alfuzosin (a new alpha-1-receptor blocking agent) in
patients mainly presenting with micturition complaints
of an irritative nature and confirmed urodynamic
abnormalities. Eur Urol 1992;22:222–7.
[28] Neal DEJ, Moon TD. Use of terazosin in prostatodynia and
validation of a symptom score questionnaire. Urology
1994;43:460–5.
[29] Nickel JC, Narayan P, McKay J, Doyle C. Treatment of
chronic prostatitis/chronic pelvic pain syndrome with
tamsulosin: a randomized, double-blind trial. J Urol
2004;171:1594–7.
[30] Barbalias GA. Prostatodynia or painful male urethral syndrome? Urology 1990;36:146–53.
[31] Barbalias GA. Clinical and therapeutic guidelines for
chronic prostatitis: from bacteriological importance to
neuromuscular considerations. Eur Urol 2000;37:116–7.
[32] Canale D, Turchi P, Giorni PM, Scaricabarozzi I, MenchiniFabris GF. Treatment of abacterial prostatovesiculitis
with nimesulide. Drugs 1993;46(Suppl 1):S147–50.
[33] Olavi L, Make L, Imo M. Effect of finasteride in patients
with chronic idiopathic prostatitis. A double-blind, placebo-controlled, pilot study. Eur Urol 1998;33(Suppl 1):24
(abstract no. 96).
[34] Nickel JC, Downey J, Pontari MA, Shoskes DA, Zeitlin SI. A
randomized placebo-controlled multicenter study to
evaluate the safety and efficacy of finasteride for male
chronic pelvic pain syndrome (category IIIa chronic abacterial prostatitis). BJU Int 2004;93:991–5.
[35] Rugendorf EW, Weidner W, Ebeling L, Buck AC. Results
with pollen extracts (Cernilton N) in chronic prostatitis
and prostatodynia. Br J Urol 1993;71:433–8.
[36] Elist J. Effects of pollen extract preparation prostat/poltit
on lower urinary tract symptoms in patients with chronic
non bacterial prostatitis/chronic pelvic pain syndrome: a
randomized, double-blind placebo-controlled study. Urology 2006;67:60–3.
[37] Kaplan SA, Volpe MA, Te AE. A prospective, 1-year trial
using saw palmetto versus finasteride in the treatment
of category III prostatitis/chronic pelvic pain syndrome.
J Urol 2004;171:284–8.
[38] Shoskes DA, Zeitlin SI, Shahed A, Raifer J. Quercetin in
men with category III chronic prostatitis: a preliminary,
prospective, double-blind placebo-controlled trial. Urology 1999;54:960–3.
24
eau-ebu update series 5 (2007) 16–25
[39] Lee RA, West RM, Wilson JD. The response to sertraline in
men with chronic pelvic pain syndrome. Sex Transm
Infect 2005;81:147–9.
[40] Nickel JC, Johnston B, Downey J, et al. Pentosan
polysulfate therapy for chronic non bacterial prostatitis
(chronic pelvic pain syndrome category IIIa): a
prospective multicenter clinical trial. Urology 2000;56:
413–7.
[41] Nickel JC, Forrest JB, Tomera K, et al. Pentosan polysulfate
sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo-controlled
study. J Urol 2005;173:1252–5.
[42] Nordling J. Pelvic pain and interstitial cystitis: therapeutic strategies, results and limitation. EAU Update Series
2004;2:179–86.
[43] Pavone-Macaluso M, Abbadessa D, Serretta V, Pavone C,
Vella M, Rinella M. Sindromi prostatitiche croniche (SPC),
chronic pelvic pain syndrome e cistite interstiziale. Semplice analogia o unità patogenetica? Risultati di uno
studio pilota sul trattamento delle SPC con associazione
di un anti-istaminico ed un eparinoide. Abstract from the
78th Congress of the Italian Society of Urology, Palermo,
2005. p. 56.
[44] De Rose AF, Gallo F, Giglio M, Carmignani G. Role of
mepartricin in category III chronic prostatitis/chronic
pelvic pain syndrome: a randomized, prospective placebo-controlled trial. Urology 2004;63:13–6.
[45] Persson BE, Ronquist E, Ekblom M. Ameliorative effect of
allopurinol on non-bacterial prostatitis: a parallel doubleblind controlled study. J Urol 1996;155:961–4.
[46] Zermann DH, Ishigooka M, Schubert J, Schmidt RA. Perisphincteric injection of botulinum toxin type A. A treatment option for patients with chronic prostatic pain? Eur
Urol 2000;38:393–9.
[47] Cho YH, Lee SJ, Lee JY, et al. Changes in serum and
prostatic zinc concentrations in rats after intraprostatic
injection of zinc: comparison of two forms of zinc delivery. Int J Urol 2000;9:681–7.
[48] Kerbl K, Zisch R. Local transrectal treatment for chronic
nonbacterial prostatitis and prostatodynia. Initial clinical
experience. Techn Urol 2000;6:22–5.
[49] Nickel JC, Downey J, Feliciano AE, Hennenfent B. Repetitive prostatic massage therapy for chronic refractory
prostatitis: the Philippine experience. Techn Urol
1999;5:146–51.
[50] Nickel JC, Alexander R, Anderson R, et al. Prostatitis
unplugged? Prostatic massage revisited. Techn Urol
1999;5:1–7.
[51] Ateya A, Fayez A, Hani R, Zohdi W, Gabbar MA, Shamloul
R. Evaluation of prostatic massage in treatment of chronic
prostatitis. Urology 2006;67:674–8.
[52] Rowe E, Smith C, Lavernick L, Elkabir J, Witherow RO, Patel
A. A prospective, randomized, placebo controlled, doubleblind study of pelvic electromagnetic therapy for the
treatment of chronic pelvic pain syndrome with 1 year
of follow-up. J Urol 2005;173:2044–7.
[53] Shafik A. Letter to the Editor. Re: Rowe et al. (152). J Urol
2006;175:1964–5.
[54] Servadio C, Leib Z. Chronic abacterial prostatitis and
hyperthermia: a possible new treatment? Br J Urol
1991;67:308–11.
[55] Nickel JC, Sorensen R. Transurethral microwave thermotherapy for non-bacterial prostatitis: a randomized double blind sham controlled study using new prostatitis
specific assessment questionnaire. J Urol 1996;155:1950–5.
[56] Kastner C, Hochreiter W, Huidobro C, Cabezas J, Miller P.
Cooled transurethral microwave thermotherapy for
intractable chronic prostatitis. Results of a pilot study
after 1 year. Urology 2004;64:1149–54.
[57] Chen R, Nickel JC. Acupuncture ameliorates symptoms in
men with chronic prostatitis/chronic pelvic pain syndrome. Urology 2003;61:1156–9.
[58] Geramoutsos I, Gyftopoulos K, Perimenis P, et al. Clinical
correlation of prostatic lithiasis with chronic pelvic pain
in young adults. Eur Urol 2004;45:333–8.
[59] Barnes RW, Hadley HL, O’Donoghue EPN. Transurethral
resection of the prostate for chronic bacterial prostatitis.
Prostate 1982;3:215–9.
[60] Mehik A, Hellström P, Sarpola A, Lukkarinen O, Jarvelin
MR. Fears, sexual disturbances and personality features
in men with prostatitis: a population-based cross-sectional study in Finland. BJU Int 2001;88:35–8.
[61] Chen WM, Yang CR, Ou YC, Ho HC, Su KY, Cheng CL.
Combination regimen in the treatment of chronic prostatitis. Arch Androl 2006;52:117–21.
[62] Nickel JC, Downey J, Arden D, Clark J, Nickel K. Failure of
monotherapy strategy for difficult chronic prostatitis/
chronic pelvic pain syndrome. J Urol 2004;172:551–4.
[63] Nickel JC. New developments in prostatitis. AUA News
2006;11:14–7.
CME questions
Please visit www.eu-acme.org/europeanurology
to answer these CME questions on-line. The CME
credits will then be attributed automatically.
1. The chronic prostatitis syndrome:
A. Is a well-defined disease with uniform features
B. Comprises a variety of symptoms
C. Is genetically transmitted
D. Prognosis and treatment are identical in all
cases
2. The treatment with a-blockers in CPS:
A. Brings about a symptomatic improvement in
all NIH categories of patients
B. Is useful only in improving urinary flow
C. May reduce intraprostatic reflux
D. Stimulates apoptosis
3. Intraprostatic injection of antibiotics:
A. Is a good therapeutic measure only if cortisone
is added
eau-ebu update series 5 (2007) 16–25
B. Reaches uniform concentration in the whole
prostate gland
C. Has not been conclusively proven to be
effective
D. Is safe, painless, and devoid of side-effects
4. The choice of an antibacterial agents for the
treatment of chronic bacterial prostatitis is made
according to:
A. In vitro sensitivity test
B. Knowledge that aminoglucosides are active on
gram-negative bacteria
C. Knowledge of pharmacokinetics of drugs and
capability to cross a blood–prostate barrier
D. Knowledge of side-effects of the different drugs
5. Neurotic manifestations, anxiety, and depression
are frequent among patients with refractory CPS.
What is the best solution?
A.
B.
C.
D.
25
Advise psychotherapy
Advise psychoanalysis
Administer antidepressants
Try to improve doctor–patient relationship
and gain confidence
6. Prostatic massage has been proposed as a
therapeutic method for treatment of CPS. Which
is the most likely explanation?
A. It ‘‘unplugs’’ prostatic ducts from inflammatory debris
B. It increases blood supply
C. It facilitates penetration of antibiotics in the
prostate
D. It has a placebo-like effect
`