1. health and fitness
2. disease
3. incontinence

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TREATMENT OPTIONS FOR
BENIGN PROSTATIC
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HYPERPIASIA (BPH)
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A report by the
Australian Health Technology
Advisory Committee, 1994
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N a t i o n a l H e a l t h a n d M e d i c a l Research C o u n c i l
NHMRC
,
0 Commonwealth of Australia 1994
ISBN 0 644427833
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This work is copyright. It may be reproduced in whole or in part for study
or training purposes subject to the inclusion of an acknowledgement of the
source and no commercial usage or sale. Reproduction for purposes other
than those indicated above, requires the written permission of the
Australian Government Publishing Service, GPO Box 84,
Canberra ACT 2601.
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The objectiveof the National Health and Medical Research Council is to
advise the Australian community on the achievement and maintenance of
the highest practicable standards of individual and public health and to
foster research in the interests of improving those standards.
National Health and Medical Research Council documents are prepared by
panels of experts drawn from appropriate Australian academic,
professional, community and government organisations. NHMRC is
grateful to these people for the excellent work they do on its behalf. Often,
such work is performed m addition to other substantial work commitments.
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Executive summary
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Benign prostatic hyperplasia (BPH)is a non-cancerous enlargement of the prostate gland
which can cause obstruction of the urethra so that the patient has difficulty passing
urine. The relationship between the size of the prostate, obstruction and symptoms is
complex.
This disorder usually only affects men over 50 years of age. Over half of men over 50
years of age have symptoms caused by BPH and 25 per cent to 30 per cent ultimately
may have surgery.
The etiology of BPH is poorly understood. Two major factors necessary for the onset of
BPH are age and normal testicular function. Many potential risk factors for BPH have
been investigated but no causal relationships established.
The conventional treatment for BPH is surgery. Transurethral resection of the prostate
(TURP)has been the preferred operative procedure. Recently, however, alternatives to
TURP have been developed and are at various stages of development and introduction
to Australia.
There are over 25 000 TURPs undertaken in Australia annually.
The introduction of some of these alternative therapies is likely to add to, rather than
replace, existing therapies. This could result in a cascade of treatments, and a potential
widening of indications for treatment, with associated cost implications.
While the results obtained from a number of the alternative treatments to TURP are
promising, they are at an early stage of development and not yet proven.
There is very limited data on the cost effectivenessof the new technologies. Because of
their early stage of development and the absence o f information on failure rates, retreatment rates and the mix of technologieswhich might prevail, it is difficult to arrive at
meaningful cost data on the range of therapeutic alternatives in the treatment of BPH.
The introduction of these technologieswithout adequate data on costs, safety and
effectivenessis of concern.
The imminent availability of alternative treatments for BPH has highlighted the need for
more rigorous assessment of urinary obstruction to enable better selection of treatment
option.
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The Working Party therefore has these recommendations:
Recommendation 1
Guidelines of best clinical practice for the diagnosis and treatment of BPH be drawn up
as a matter of urgency with representation from the Royal Australian College of General
Practitioners, the Urological Society of Australasia, and expertise provided by consumer
bodies and health economists. Recent recommendations adopted by a WHO-sponsored
Consensus Committee on BPH could serve as a basis for such guidelines in Australia.
Recommendation 2
The consumer statement in Appendix 2, providing information on BPH and the options
available for its treatment, should be disseminated widely.
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Recommendation 3
The introduction of new technologiesfor the treatment of BPH should be managed in a
way that clearly identifies whether they are established, or the degree to which they are
experimental or emerging.
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Recommendation 4
As a matter of urgency, AHTAC should consider the need for a mechanism to ensure
that new treatment technologiesfor BPH have had adequate trials before they are
introduced into routine clinical practice, or, alternatively, that they are introduced under
trial conditions involving urological professional bodies.
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Recommendation 5
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Funding of trials should generally be from government or industry. Medicare rebates
should be available for technologiesshown to be safe, effective and cost effective, and
which can be regarded as established. The Working Party believes that Medicare rebates
should also be available for such established therapies which are being further evaluated
within controlled trials.
vi
Introduction
Benign prostatic hyperplasia (BPH)is the non-cancerous enlargement of the prostate, usually
beginning in the fifth decade of life in men and which in many men may cause obstruction to
urinary flow.
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BPH has been one of the most frequent reasons for elderly men undergoing surgery and it is
only recently that the high prevalence of the condition in apparently well men has been
described.
Surgery has been the standard method of treatment for BPH and transurethral resection of the
prostate (TURP),an endoscopic surgical procedure, has been the ‘gold standard for the
treatment of this condition. However, because of the morbidity associated with the surgical
procedures, alternative treatments are being developed and are coming into increasing use.
SC
Because of the high prevalence of BPH and the demographic shift to an ageing population,
together with concern about the speed of development and introduction of these technologies
without adequate evaluation of their effectiveness, the Australian Health Technology
Advisory Committee (AHTAC)decided to review the literature in this area to assess the
efficacy, safety and costs of the treatment options for BPH, and to consider the possible roles
that they may occupy.
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The AHTAC noted that the Australian Institute of Health and Welfarehad already provided
an overview of the technologies, as well as making some very preliminary cost estimates for
some of the alternative treatments for BPH.
The AHTAC formed a Working Party to examine the technologies used m the treatment of
BPH. The terms of reference for the Working Party are in Appendix 1.
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The Working Party’s report is intended to provide an overview of current and emerging
treatments for the management of BPH. Issues related to the introduction of new technologies
in BPH have been raised as an instance of the need for a more rational introduction of new
technologiesin the arena.
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The Working Party drew extensively on the Institute’s study, and, in addition, considered the
issues which might need to be addressed by governments, health professions and the
community during the introduction of these technologies. Suggestions on how a rational
introduction of the technologies could be done have also been made.
1
Benign Prostatic Hyperplasia (BPH)
The prostate
The prostate gland, which produces most of the fluid that makes up the semen, is just below
the bladder and in front of the rectum and surrounds the first two to three centimetres of the
male urethra. The urethra passes through the prostate and when enlargement of the prostate
occurs, the urethra becomes compressed and can obstruct the flow of urine.
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The prostate slowly increases in size from birth until puberty, when it enlarges rapidly.
Thereafterit remains constant in size until about the age of 45 or 50. The prostate may then
undergo benign enlargement, in which case its volume begins to increase at a rapid pace and
may continue to increase through the life of the patient. Alternatively, it may not show this
pathologic change, in which case it begins to atrophy and progressively decreases in size.
SC
There is not a close correlation between the symptoms of prostate enlargement and the size of
the prostate.
Etiology and epidemiology of BPH
The etiology and epidemiology of BPH have been covered in recent articles. 4,5
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Although the etiology of BPH is poorly understood, it is clear that the two major factors
necessary for the onset of BPH in men are age and normal testicular function. Consequently,
much research is being directed at identifying a hormonal cause.
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Risk factors for BPH
Many studies have attempted to identify risk factors for BPH. Factors such as use of tobacco,
alcohol consumption, history of kidney damage, celibacy,specificblood groups and
conditions such as coronary heart disease, cerebral vascular disease, hypertension, diabetes
mellitus, and cirrhosis of the liver have been examined. However, because there is no wellaccepted clinical case definition of BPH, there is insufficientevidence to regard any of these
factors as causal.
Incidence and prevalence of BPH
Estimatesof the age-specificprevalence of BPH vary widely depending on the way the
disease is defined. Estimates have been obtained from autopsy studies, disease diagnosed
clinically on the basis of a medical examination and rectal examination, medical examinations
to qualdy for life insurance and from community-based studies. The interpretation of the
data is hampered by a lack of standardised diagnostic criteria and other difficulties. It is
evident that the disease, however defined, is prevalent in a substantial fraction of men aged
50 years and older, that prevalence increases with age, and that differences in prevalence
2
among studies could be because of different case definitions, or differencesin the
populations studied, or both.
In the USA more than half of all men over 50 years have symptoms caused by an enlarged
prostate and 25 per cent to 30 per cent ultimately require surgery. BPH accounts for an
estimated 1.7million physician office visits a year in that country. Urologists in the USA
perform about 400 000 TURh each year at a cost to the insurers of $US10 000 to $US12 000
per procedure, so up to $US4.8 billion is spent each year to relieve blocked urinary tracts, of
which some $1.6billion is for hospitalisation.
Drummond et al. estimated the economic burden of treated BPH in the United Kingdom.
Their estimates showed that the cost to the NHS and Department of SocialSecurity is
between €54 million and €71 million.The maximum cost to the NHS (€67.89million)
represented approximately 0.4 per cent of NHS expenditure.
Symptoms of BPH
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In Australia, Medicare data (which covers private patients treated in public or private
hospitals) for 1993-94shows that 13957 TURPs were performed at a cost to Medicare of
$8.6 million, representing 0.2 per cent of total Medicare Benefits-paid. Data available from
the Hospital Morbidity Collectionsprogram indicates that the total number (including
public and private) of TURPs performed in Australia is more than 25 000 procedures
a year. lo
Patients may present with a symptom complex called ‘prostatism’that may include:
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diminution in the calibre and force of the urinary stream;
hesitancy in initiating voiding;
inability to terminate micturition abruptly, with postvoiding dribbling;
a sensation of incomplete bladder emptying; and
occasionally, urinary retention.
These are known as obstructive symptoms. They are distinguished from irritative lower
urinary tract symptoms that include dysuria, frequency nocturia and urgency
l
It is important to note that none of these symptoms is exclusivelyrelated to either
obstruction or irritation and none clearly identifies men with obstructive uropathy related
to prostatic hypertrophy. Thus men need to be carefully selected on clinical grounds to
ensure that their symptoms are indeed due to urinary obstruction.
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The degree of difficulty caused by BPH is often quantified using a symptom score system,
such as the newly developed American Urological Association symptom score. l2 There is
no absolute score in whichever scoring system is used that indicates the need for
intervention.
Diagnostictools for assessing BPH include physical examination, cystoscopy intravenous
pyelography, urodynamic studies, and transrectal prostatic ultrasonography
Patients usually seek medical advice for one of three reasons -nocturia (excessive
urination at night), concern about prostate cancer, and because they are bothered by their
symptoms. Patients may have a combination of these symptoms, which may or may not
progress in severity The proportion of men who have symptoms, but who do not seek
medical advice, is not known.
3
Clinical progression of BPH
Most information on the clinical course of BPH has been obtained from relatively small
series of patients followed in urology clinics over various periods for symptoms of
prostatism. These studies have shown that the clinical course of BPH in individual patients
is highly variable over time, whether measured by symptoms or by urinary flow rates. An
appreciable fraction of patients improve spontaneously without treatment. Because of the
small sample size and the high degree of intra-individual variability in the diagnostic
measures used to assess the disease, most studies have had little statistical power to
quantify what factors are relevant to long-term prognosis.
Complications of BPH
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Potential complicationsof the outflow obstruction and urinary residuals caused by BPH
include bladder wall muscular hypertrophy leading to trabeculation and formation of
diverticula. When urine remains in the diverticula of the bladder, bacterial overgrowth may
ensue, leading both to urinary tract infection and formation of bladder calculi. Reflux into
the ureters may eventually occur, with resulting hydronephrosis and sometimes
pyelonephritis with permanent renal damage. Finally acute episodes of complete urinary
retention may develop, necessitatingemergency surgical intervention. The main sources of
morbidity and mortality with BPH are renal .failure, urologic infections leading to
pyelonephritis and sometimesto sepsis, acute urinary retention and mortality from
complicationsof therapy. Quantitative epidemiologicalinformation on the likelihood of
these complications and on what risk factors may be most important is lacking.
4
Management options for BPH
Transurethral resection of the prostate (TURF'), a surgical, endoscopic procedure, has been
the 'gold standard for the treatment of bladder outlet obstruction for many years.
However, the incidence of clinically significantpost-operative complications, treatment
failures and re-operation rates have encouraged the search for safer and more effective
treatment options for BPH.
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Table 1categorises the.different techniques becoming available for the management of BPH.
Table 2 provides a summary of the technologiesand their clinical status. The clinical status
of these treatment options is discussed in the following sections.Table 3 provides a
summary of the literature cited on the treatment options for BPH.
Table 1: Categories of management options for BPH
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Pharmacologic
Mechanical
Open surgery
Laser
Alpha blockers
Stents
Transurethral
resection (TURF')
Microwaves
Hormones
Balloon dilation
Transurethral
incision (TUIP)
High intensity
focused ultrasound
Surgical
Watchful waiting
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Thermal
No intervention
Cryosurgery
Transurethral
needle ablation
(TUNA)
5
Ultrasonic
aspiration
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Pyrotherapy
Phytopharmaceuticals
Watchful waiting
The natural history of BPH is not well understood. In most patients, the condition does not
progress from mild or moderate symptomatic manifestations to a more severe form. Also,
although complete resolution of symptoms of prostatism is uncommon, progression to
more serious sequelae such as urinary retention likewise is infrequent. Severe
manifestations of BPH are prkent at the time of initial assessment in approximately 5 per
cent of all older men for whom intervention for BPH is considered. l3 In the British and
Danish health servicesonly l-2 per cent of patients waiting for surgery develop retention
per year. l4
Izaacs l5 has reviewed the small number of existing reports of the natural history of BPH,
and found that approximately 20 per cent of patients tend to improve and 20 per cent tend
to deteriorate after initial assessment.The course of the disease waxes and wanes for the
remaining 60 per cent. He concluded that those patients who have the greatest degree of
spontaneous improvement usually have had a history of symptoms of less than six months.
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6
Tissue is heated transurethrally to temperatures ranging from 45°C to 60°C.
Hyperthermia is achieved either via a tramrectal or transurethral
approach. The tissue is heated to between 42°Cand 44°C.
May be undertaken by suprapubic, retropubic or perineal approaches.
Prostate is resected using electrocauteryunder direct vision.
Incisionsare made in the prostate and bladder neck.
These lasers (ultrasound-guided or under visual control)are introduced
transurethrally to coagulate the tissue.
Bare fibrescarrying the low power (<15W)laser are placed in contact
with the tissue to shmk the prostate by coagulation.
150000 with a once-only
use probe costing 1300
10000-750000
Equipment cost ($A)
Considerable morbidity has been reported.
Either expandable tubular mesh or removable spiral stents are placed in
the urethra to dilate the vessel.
A balloon catheter is introduced in the prostatic urethra and inflated.
Transrectalprobe dinxts ultrasound to the prostate and heats tissue
to between 80°C and 9 O C
Highly focused ultrasound shock waves generated outside the body are
used to destroy tissue deep within the body.
The device disrupts the tissue by repetitive striking and fragments are aspirated.
Sub-zerotemperatures are used to destroy tissue.
A pair of needles, through which pass RF waves, are placed in
contact with the tissue.
Stents
Balloon dilation
High intensity focused
ultrasound
Pyrotherapy
Ultrasonic aspiration
Cryosurgery
Transurethral needle
ablation (TUNA)
40 000 plus 1 000 per
patient for needles.
40 000
113OoOO
500 000
1000
2000
Lifetime commitment and complianceis required.
Long-term effects of drug usage are unknown.
These drugs (for example, Hytrin) affect the muscular tone of the prostate
capsule to alleviate voiding problems.
2) Alpha blockers
Trials are in beginning in Australia in three centres.
There is renewed interest in this technology.
We are not aware o f results using this technology.
Early results on few patients are encouraging,but
the technique for treatment of BPH is experimental.
Few patients have been treated. The technology i s
experimental.
Clinicaltrials have begun in the USA but
no results have yet been published.
Recent assessmentshave concluded that the technology
is experimental.
Lifetime commitment and complianceis required.
Long-termeffectsof drug usage are unknown.
Undergoing trials in three centres in Australia for
the past three years.
This therapy (for instance, the drug Proscar)is used to block testosterone’s
growth-stimulating effect on the prostate.
Medical treatment
A limited trial in progress in Australia.
The technique is experimental.
1) Hormone therapy
150000
Trials are under way in Australia and overseas.
Short-term results are only available.The technique is
considered experimental at this stage.
Number of patients treated so far is extremelylow.
Procedure is still experimental.
Treatmentcomprises one session of one hour.
Results not as good as TURP and short-term
outcomes are only available.
Between C10 treatment sessions,each of one hour.
The use of this technique is diminishing and
thermotreatment is being preferred.
Used for large prostates.
Most common procedure for prostatectomy.
Used for small prostates. Procedure becoming more
popular.
Comments
Observation without surgical treatment is a more
reasonable option than previously believed.
A sapphire-tipped probe is dragged over the prostate to vaporise it.
D
DE
3) Contact laser surgery
2) Side-fimg lasers
Laser irradiation
1) Interstitial laser
coagulation
2) Thermotreatment
Microwaves
1) Hyperthermia
Surgery
1)Open surgery
2) Transurethral resection
3) Transurethral incision
Description
The natural history of BPH is not well understood. BPH usually does
not progress from mild to a more severe form.
IN
Watchful waiting
r
2: Summa1 of management
options for the treatment of BPH
-
SC
Table
RE
Table 3: Summary of literature c i t e d on options for therapy for BPH
I
2ference
1
1 ;;i~;;; 1
I
I
I
Type.ofstudy
of
Follow-up perkd
(months)
Results reported
Laser (CLS)
20
ns
All patients experienced
marked improvement.
32'
Laser (CLS)
Prospective
No controls
25
u p to 11
Successful results were
noted in 20 patients (80%).
33'
Laser (ILC)
Prospective
No controls
56
u p to 12
Success in over 80% o f
patients.
34'
Laser (ILC)
Prospective
No controls
11
u p to 12
Encouraging.
35'
Laser (ILC)
Prospective
No controls
20
ns
All patients experienced
marked improvement.
36'
Laser (TULIP)
Prospective
No controls
200
6
Success rate of 82.5%.
37
Laser (TULIP)
Prospective
No controls
28
12
Significant improvement in
subjective and objective
symptoms.
40'
Laser (TULIP)
Randomised
100
3
Procedure appears safe and
effective for BPH.
41'
Laser (VLAP)
Prospective
No controls
200
up to 6
Significant reductions in
symptom scores.
ficrowaves
SC
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31'
30
Hyperthermia
Prospective
No controls
43
Hyperthermia
Prospective
No controls
72
44
Hyperthermia
Prospective
No controls
133
4
5
'
Hyperthermia
Prospective
No controls
46
Significant improvement of
objective voiding parameters
achieved in only 2 patients.
1
IN
42
40% remained catheter-free.
up to 96
59% of those with catheter had
satisfactory outcome; those who
had severe symptoms (65%)
showed improvement.
41
6-48
65% initial success and of those 9
were catheter-free.
Hyperthermia
Prospective
No controls
15
3-7
80% (12 patients) showed
improvement.
47
Hyperthermia
Prospective
Randomised
Controlled
68
3
4
8
'
Hyperthema
Retrospective
150
24
Treatment did not resolve obstructior
49
Hyperthermia
Prospective
No controls
32
3-19
72% (25patients) catheter-free.
50
Hyperthema
Comparative
No controls
36
10-28for transurethral
7-16 for transrectal
Improvement was observed in both
groups but noted more frequently in
the transurethral group.
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12
68%subjective improvement in
treatment group with 33%
improvement in sham group.
8
Table 3 (cont.): Summary of literature cited on options for therapy
for BPH
.
I'ype of study
Number of
patients
Follow-up period
(months)
Results reported
3
18 of 22 patients who received
microwave treatment were successfully
treated.
40
Hyperthermia
Multicentre
Prospective
Double blind
Randomised
Controlled
200
over 12
Hyperthermia does not ameliorate the
objective parameters of urinary
obstruction.
Thermotherapy
Prospective
No controls
300
upto6
Good subjective response in most
patients. Objective improvement not so
impressive.
Thermotherapy
Prospective
No controls
135
6
133 patients improved but flow rate
improvements were modest.
Thermotherapy
Prospective
No controls
Multicentre
60
upto3
Symptomatic improvement occurred
with time.
Thermotherapy
Prospective
150
12
Results durable out to one year,
Thermotherapy
Prospective
No controls
336
u p to 12
63% experienced subjective
improvement but objective
improvement was less pronounced.
Thermotherapy
Prospective
Randomised
Comparative
79
u p to 24
Improvement was less pronounced afte
thermotherapy.
40
3
Treatment group showed 70% decrease
in symptom score while the sham g r o q
experienced no significant change.
6
Significant improvement in both group:
but more durable in the treatment
PUP.
Thermotherapy.
Prospective
Randomised
Controlled
46
Terazosin
Prospective
Randomised
Controlled
57
Terazosin
Multicentre
Randomised
Controlled
Double-blind
137
Significant improvement m mean flow
rate and peak flow rates. But
symptomatic response not statistically
significant from placebo.
Terazosin
Prospective
Randomised
Controlled
313
Significant improvements were observec
in all symptom score parameters. These
were dose related.
Terazosin
Prospective
No controls
45
Significant increases were seen in all
patients in peak urine flow rates and in
symptom scores. A 2-year follow-up of
9 patients showed sustained
improvement.
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u p to 24
DE
7
IN
Thermotherapy
Prospective
Randomised
lControlled
SC
RE
Hyperthermia
Prospective
1Double blind
Randomised
,Controlled
47% of patients showed durable clinical
response to terazosin.
24
L
9
Table 3 (cont.): Summary of literature cited on options for therapy for BPH
Reference
'
Type of study
Indoramin
Prospective
No controls
67
Terazosin
Multicentre
Prospective
Randomised
Controlled
Finasterid
Prospective
Randomised
Controlled
Pollen extract
Prospective
Controlled
Double-blind
71
74
Stents
Follow-up period
(months)
190
upto6
150
u p to 40
77
Prospective
No controls
29
u p to 11
79
Prospective
No controls
21
u p to 16
60
u p to 24
SC
Prospective
No controls
27
IN
Prospective
No controls
249
8
8
'
Prospective
No controls
61
89*
Prospective
No controls
30
ns
29
6
qwfierapy
9
Prospective
Randomised
No controls
Prostatic spiral is a useful alternative to
a catheter but life-long follow-up is
necessary.
Stent was removed in 14 patients (48%)
and calcification was a late
complication.
There was a gradual decline in peak
and median urine flow rates over the
follow-up period.
Effective in some forms of prostatism.
Successful in 25% of patients.
Technology does not offer any
advantage over established methods.
Safe and effective,but not appropriate
f o r all uatients.
Technology offers a safe and efficient
option for BPH.
DE
Ultrasonic aspiration
91'
Symptom scores decreased in the
treatment group but due to sample size
did not reach statistical significance.
Extract has a beneficial effect on BPH.
76
No controls
Results reported
There was an improvement in overall
symptom scores and in peak flow rates i
41 patients (75%)who could be assessed
Improvements observed in symptoms in
treatment groups were not statistically
significant from the placebo group.
RE
66
Number of
patients
Technology is feasible in humans.
Procedure appears to be as efficacious
as TURF!
D
Notes: * denotes abstract
ns = not stated
The difficultywith urinary obstruction is that the indications for prostatectomy for symptoms
are imprecise.There is much debate on whether these symptoms are caused by bladder
outflow obstructionand whether these symptoms and s i p s indicate the need for
prostatectomy. This is reflected m the widespread variations in rates of prostatectomy among
small geographicareas m the United States and in other Western countries, which have been
interpreted as evidencefor professionaluncertainty concerning the appropriate method for
treating BPH. l6
10
For most patients with BPH, no objective set of rules will assure that surgery is being used
‘appropriately’.In an interview study, Wennberg l7 reported that patients with moderate and
severe symptoms of BPH were asked how much they were bothered by their symptoms. He
found considerable differencesamong individual patients. Even some severely symptomatic
patients were not very much bothered with their symptoms. Moreover he found differences
in willingness to undertake the risk of operation which did not correlate well with the
severity of symptoms. He realised that there are no objective rules that allowed the physician
(much less a third party) to classify such patients according to whether the operation is
’appropriate’or ‘inappropriate’ for an individual. He concluded that for uncomplicated BPH
patients with moderate and severe symptoms (which include most patients) rational
decision-makingrequires informing physicians and individuals of the risks and benefits of
prostatectomy and its alternative, watchful waiting.
RE
Mehl l* reported that involving the patient in treatment decision-makingreduced the rate of
surgery for BPH by 44 per cent. Interactive videodisc technology was used to promote patient
participation and was designed to be used when a diagnosis was made that involved
treatment options that the patient must choose from. In such situations, patients’ choices were
influenced by their lifestyles and personal preferences.
SC
Fowler et al. M have noted that the medical literature shows a clear ‘average’advantage for
prostatectomy when comparing the relative value of prostatectomy and watchful waiting for
improving symptoms. However the magnitude of the effect of the operation on symptoms
and quality of life has not been well documented. Barry et al. l9 performed a decision analysis
to compare the expected outcomes of immediate TURP compared to watchful waiting. They
concluded that patient preference should be the dominant factor in the decision whether to
perform a prostatectomy.
Although more information is needed, it is clear that observation without surgical treatment
is a more reasonable option than previously believed.18
DE
IN
However Catalona 2o cautions that the potential side effects of watchful waiting should not be
overlooked. Some men may harbour other serious disorders that pass for prostatism, and
patients with long-standing obstruction may suffer urinary tract deterioration and loss of
renal function. 2o He further comments that it is not advisable, therefore, to treat symptomatic
patients with drugs such as alpha blockers, or even watchful waiting without appropriate
urologic evaluation.
Surgical procedures
D
Surgical methods of treatment for BPH include TURP,transurethral incision of the prostate
(TUIP)and open prostatectomy by a suprapubic, retropubic or perineal approach. Although
performed in 40-70 per cent of patients with BPH during the 197Os, by 1986TURP had
become the procedure of choice for 95 per cent of prostatectomies in US non-Federal shortstay hospitals. 21
Open prostatectomies are typically reserved for men with prostates too large to permit
transurethral resection.Details of these surgical procedures are provided in standard
urologicaltexts.
TURP is effectivein improving obstructing symptoms in 75-85per cent of patients. The
duration of improvement is variable and re-operations are required at a rate of approximately
2.5 per cent per year, a rate that remains constant during eight years of follow-up after
original resection.
11
While the postoperative mortality of TURP is low (between 0.2-0.05per cent 23) there has
been some concern regarding higher long-term mortality rates following the procedure. 24,25
Dribbling and urge incontinence (20-50 per cent), impotence ( 5 4 0 per cent), retrograde
ejaculation(50 per cent), urethral stricture (5-15 per cent), chronic urinary tract infection (less
than 5 per cent) and haemorrhage (5 per cent) have all been reported following TURP.
Many of the men afflicted by BPH who require treatment are elderly and frequently have
concurrent medical conditions that may markedly increase the operative risks. In addition,
the potential surgical morbidity may deter men fromundergoing treatment until urinary
obstruction is so advanced that intervention becomes essential.
S
RE
A recent development in TURP in the US is the performance of the procedure in an outpatient
setting. 2 7 3 McLoughlin and Kinahan 27 reported on 150patients treated by TURP in an
outpatient setting and concluded that the method proved to be safe and cost effective. They
commented that the decision whether to perform outpatient TURP depends on the health of
the patient, the ability of the family to care for him, the home environment and the
motivation of the patient to undergo the procedure in this manner. The implications of such
developments for cases in Australia are unclear, and the feasibilityof such an outpatient
procedure would need careful assessment.
TUIP is increasinglyused to treat small, obstructive prostates (less than 30 g). The procedure
is a modified version of TURP in that one or two incisions are made in the prostate and
bladder neck. No tissue is resected. Studies comparing TUIP with TURP have found TUIP
significantlybetter than TURP in terms of shorter operating time, less anaesthesia and blood
loss and shorter length of stay in hospital. 29,30 The procedure is preferred by younger men
because it results in only one fourth of cases of retrograde ejaculationas does TURP
Laser therapy
ND
CI
In summary, surgery remains the standard treatment for BPH, with TURP being the most
common procedure.
A number of different methods to deliver laser energy to benign and malignant prostatic
tissue are being explored. These include contact laser surgery (CLS)interstitial laser
coagulation (ILC),transurethral laser-induced prostatectomy (TULIP)and visual laser
ablation of the prostate (VLAP).
ED
Contact laser surgery (CLS)
In CLS laser energy is delivered to a sapphire-tip probe which is in contact with the target
tissue transurethrally. Advantages claimed for this procedure are the shortened length of
hospital stay (overnight) and less bleeding. 31,32
A limited trial using this technology on about 30 patients is in progress in Victoria,
The technologyis in its early stage of development.
Interstitial laser coagulation (ILC)
Tissuecoagulation is produced by low power laser light transmitted by fine fibres inserted
interstitially.Shrinkage of the prostate takes place within 6-8 weeks of treatment. The number
of patients treated so far is very low and only short-term results have been reported. 33-35
12
Transurethral laser-induced prostatectomy (TULIP)
A number of commercial devices have been developed to allow the deposition of laser
irradiation on the prostate transurethrally with the use of right-angled fibre delivery systems.
In this procedure a right-angled delivery optical fibre is used which is centred within the
urethra by an inflatable balloon. The laser fibre can be rotated through 360" and moved along
the length of the balloon. The objective is only to coagulate the tissue, rather than vaporise or
cut it, in order to avoid bleeding. Dead tissue sloughs away in the urine over seven weeks.
The procedure is monitored using a miniature ultrasonic imaging device mounted inside the
dilation balloon, along the laser fibre, in such a way that the laser beam is always in the centre
of the ultrasonic image. No irrigation is used, eliminating the dilution syndrome, caused by
excessiveabsorption of irrigating fluids. The dilution syndrome may produce confusion,
nausea, hypertension, seizures and/or coma.
RE
Fuselier et al. reported on the US Human Cooperative Study of TULIP which began in 1990.
Two hundred patients were enrolled in the study as of September 1992and 114 were followed
up to at least six months. For these patients the successrate was 83 per cent with an average
hospitalisation of 1.4 days, no transfusions and only 7 per cent experiencing retrograde
ejaculation.
SC
Schultze et al. 37 reported on their early results in 28 patients with symptomatic obstructive
BPH treated by TULIP and followed to one year. Significantimprovement of objective and
subjectivesymptoms was recorded. Bleeding was minimal and no transfusion was required
and two patients (7 per cent) reported retrograde ejaculation.
Visual laser ablation of the prostate (VLAP)
IN
In this procedure a fibre-opticdelivery system is used comprising a 600mm quartz fibre with
a gold-plated alloy deflecting dish glued to the tip of the fibre to reflect the beam at 90". The
procedure is carried out under direct vision using a standard cystoscope with a 30" viewing
telescope.
DE
Costello et al. ~ 3 - 4have
~
reported on their experience with the system. They found the
procedure relatively safe, simple, speedy, and attended by virtually no blood loss. They
suggested that laser ablation may offer some advantages over TURP in a selected subgroup of
patients. Patients were able to return to work immediately,while TURP patients generally
convalesce for two to four weeks before resuming work to minimise the risk of postoperative
bleeding. Voided flow rates and symptom scores measured after operation had approximated
those reached by TURF'. Preliminary results of a randomised study of 100patients comparing
TURP with laser ablation had shown a flow rate equivalence at three months. Costello et-al.
concluded that the procedure appeared safe and effective in the treatment of BPH.
D
Kabalin et al. 41 reported the use of a similar side-firing laser, on 200 patients evaluated for six
months. Preliminary results indicated significant reductions in symptom scores with
improvement in peak urine flow at three and six months.
The short-term results obtained with the use of lasers (particularlywith TULIP and VLAP) m
the treatment of BPH are promising. The reported shorter hospital stays, less bleeding and
apparent lower morbidity associated with these procedures rival outcomes experienced with
TURF! However, these are results from short-term studies and longer-term results will
determine the durability of those outcomes.
13
Microwave therapy
The prostate can be heated by microwave probes inserted transrectally or transurethrally
Microwave hyperthermia has been proposed as a treatment for BPH since the early 1980s.
While little is known in regard to the effective mechanisms of hyperthermia on the prostate, 42
it is known that diseased tissue heated to temperatures of 42°C to 44°C(108"-111"F) is more
susceptible to permanent damage than healthy tissue. The disadvantage of using these
temperatures is that the tissue needs to be exposed to the microwaves over a number of
sessions, typically five to ten, each lasting 60 minutes.
Some centres are now heating the prostate to temperatures ranging from 45°C to 60°C. This
procedure is called transurethral microwave thermotherapy (TUMTT)and is said to obviate
the need for multiple sessions for a lasting therapeutic effect.
RE
Machines have been developed to achieve temperature increases in the prostate either
transrectally or transurethrally. Details of some microwave machines available commercially
are provided in Table 4.
Table 4: Microwave therapy devices available for the treatment of
enlarged prostates
Device
Company
Prostatic
Microthermer
Leo (UK)
kostatron
Technomed
International
(France)
BSD 2000
USA
40 000
transurethral
10 000
transurethral
Method of
heating
Intraprostatic
temperature
Cooling
Number of
treatment
sessions
mixture of radiofrequencies
44.5'C
No
one (3 h r )
No
one or two
treatments
IN
Direx (Israel)
Route
SC
Thermex I1
Cost
W )
45-55Oc
Yes
one (1 hr)
transurethral
915 MHz
42-44OC
No
6-10 (1hr each)
kostathermer Biodan(Israe1)
transrectal
915 MHz
42-44OC
Yes
6-10 (1hr each)
Primus
Technomatix
(Belgium)
transrectal
915 MHz
40.5-42.5'C
Yes
6-10 (1hr each)
kostcare
Bruker (France)
40 000
transrectal
915 MHz
no data
Yes
no data
Tempron
TMA (Italy)
40 000
transrectal
Microfocus
Breakthrough
Medical (USA)
Prostalund
Dantec Medical
(Denmark)
400 000 transurethral
D
DE
1 GHz
750 000 transurethral
Yes
,
915 MHz
Source: Australian Institute of Health and Welfare
14
46-48'C
Yes
one (1hr)
Transrectal and transurethral microwave hyperthermia
While the use of transrectal and transurethral microwave hyperthermia in poor-surgical-risk
patients has produced some encouraging results 4M6, some authors have found this approach
ineffective 42*47,48 and others have concluded that further trials are required to define the role of
this technology. 49,50
To counter criticisms that previous studies using microwave hyperthermia were uncontrolled,
so that the placebo effect was not assessed, Bdesha et al. 51 reported on a prospective double
blind randomised study of 40 patients with BPH. Twenty-twopatients received a single 90minute transurethral microwave treatment using the LEO device and 18received sham
treatment. Follow-up at three months revealed that the treatment is safe, effective and well
tolerated by most patients. It preserved sexual function and antegrade ejaculation.They
commented also that TURP, however, remains the standard against which all other treatments
should be judged. No microwave treatment has been shown to relieve obstruction to the same
degree: increasesin flow rates after microwave treatment are modest compared with the
increases seen after surgery.
RE
Recently,a French technology assessment agency, Comite d’Evaluation et de Diffusion des
Innovations Technologques (CEDIT),in collaborationwith the country’s Urological
Association, undertook a multicentre prospective randomised double-blind clinical trial of
hyperthermia between February 1991and December 1992. 52 Some of the conclusions of the
study were:
l
l
l
IN
SC
it does not ameliorate the objective findings of urinary obstruction;
it requires a complementary treatment, medical or surgical, during the period of the year
followinghyperthermia treatment in 18per cent of patients;
amelioration of functional signs of BPH was observed when treatment was administered
endo-urethrally in 52 per cent of patients, but half of this relief was a placebo effect;
it does not constitute an alternative to surgical treatment, but it may be an alternative to
medical treatment by alpha1 blockers and 5 alpha reductase inhibitors in particular.
On the basis of these findings, and an economicstudy, CEDIT did not recommend the
purchase of first-generation hyperthermia devices for treatment of BPH.
l
DE
Transurethral microwave thermotherapy (TUMTT)
D
The incorporation of a cooling system for the urethra during microwave heating has enabled
the use of high-power settings to heat the prostatic tissue to temperatures greater than 45°C
without causing unacceptable pain to the patient or damage to the urethra (which is
maintained at a lower temperature). Transurethral microwave thermotherapy (TUMTT),as
this technique is called, is attracting much interest, particularly as only one treatment session
is required.
Laduc 53 reported on 300 patients treated with TUMTT. Within 48 hours of treatment, urinary
retention developed in 26 per cent of patients for which an indwellmg catheter was inserted
for one week. Preliminary results after six months showed a significantimprovement m
symptom scores. There was no significant change in residual urine and prostate volume.
Short-term results showed a good subjectiveimprovement response in the majority of cases.
Objective improvement, however, was not impressive. They concluded that long-term followup will decide if TUMTT treatment could be a good alternative for TURP.
15
Kirby et al. reached similar conclusionsfollowing a study of 135patients over six months.
They concluded that TUMTT has some efficacy, especiallyin terms of irritative symptoms in
BPH, but flow-rate improvements are modest and further controlled studies are required to
confirm these results.
Blute et al. 55 reported on a multicentre trial of TUMTT in 60 men followed-up for six weeks.
They noted that symptomatic improvement after treatment was dramatic, especially nocturia
and urgency which seemed to be the primary complaints of patients before treatment. As no
controlswere included the placebo effect could not be discounted. Peak urinary flow rates
increasedby 30 per cent, and no patient had a clinically significantincreased postvoiding
residual. Except for temporary urinary retention, the complicationswere minimal and rare.
Although high temperatures caused prostatic edema, the 40 per cent rate of catheterisation
observed was more likely due to substantial manipulation necessary for performance of the
procedure. No patient experienced retrograde ejaculationor deterioration of sexual function.
The authors concluded that longer follow-up and further study were needed to determine the
exact role of TUMTT.
SC
RE
Blute et al. have also reported on a pilot study of 150patients with BPH using the
Prostatron device with a one-year follow-up of 94 (63 pefcent) of patients. The patients
experienceddecreases in symptom scores and a mean increase of 2.9mLls (34 per cent) in
peak flow. Thirty experienced post-procedure urinary retention for 2-11 days. No patient
experiencedtreatment-limiting pain and there were no reports of retrograde ejaculation or
sigruficant change in sexual function. The re-treatment rate was less than 10 per cent and six
patients (3per cent) went to TURl?
Laduc and co-workers 57 treated 336 patients with BPH with thermotherapy and reported on
the 12month follow-up data. A subjective improvement was seen in 63 per cent of patients
but objectiveimprovement as shown by peak flow measurements before and after treatment
was less pronounced. They acknowledged that a part of the improvement would have been
due to the placebo effect, whose impact was unknown.
DE
IN
The results of a randomised study comparing TUMTT (39 patients) with TURP (40 patients)
showed that the maximum flow rate increased from 8.0 to 12.3 ml/s after TUMTT and from
7.9 to 17.7 ml/s after TURP at the 12month follow-up.58The decrease in the symptom score
after TUMTT was almost comparable to TURP and the improvement in residual urine was
slightly more pronounced after TURP. The authors concluded that significant improvements
were observed in both groups with regard to symptom score, peak flow, residual urine,
bladder capacity and detrusor pressure at peak flow. While the improvements in most
regards were less pronounced after TUMTT, complicationswere only observed after TURF'.
D
Because of the large placebo effect in the treatment of BPH, studies have been undertaken to
investigate this effect during TUMTT treatment.59Ogden et al. 59 reported on the placebo
response in a single-blind randomised study of TUMTT (21patients) versus sham treatment
(19 patients). Evaluation at three months showed that the thermotherapy group showed a
70 per cent decrease in the symptom score, a 53 per cent increase in flow rate, and 92 per cent
decreasein residual urine volume. No significantchange was seen in these mean indices in
the sham group. There was no difference in the main complication of transient hematuria
between the two groups. However there was a 22 per cent frequency of acute retention in the
TUMTT group. The results showed little significantplacebo component to the subjectiveand
objectiveimprovement that occurs in patients who received TUMTT.
16
In another study 46 patients with symptoms of BPH were randomised for TUMTT versus
sham treatment.60At three months both groups showed a good subjectiveresponse. However
this improvement was temporary in the placebo group (at six months) and ongoing after
TUMTT.
In a review of TUMTT, Perez-Castroet al. 61 concluded that the treatment produces transient
retention between 5 and 40 per cent of cases and gives prolonged relief of symptoms with
maintained increases in peak flow and reduction in bladder pressure in 40 per cent of cases. It
is not suitable for the patient with a bladder neck stenosis, middle lobe enlargement or a large
prostate gland. However for those with a gland up to 30-70 g it is a technique which holds
promise and which is likely to be developed further.
Table 3 summarises the results obtained in the literature cited on the use of microwave
therapy for BPH.
Medical treatment
SC
RE
In summary, there is widespread interest in the use of microwaves for the treatment of BPH
and the use of thermotreatment is being preferred to hyperthermia. The technology is still
undergoing development and there is considerable interest in higher operating temperatures.
The availability of this technology, particularly TUMTT, had led to a widening of indications
to include patients with non-obstructive symptoms. While the technology appears useful
there is still too little long-term data to make an unequivocal assessment of its place in the
armamentarium of methods for treatment of BPH.
.
Alpha 1
- adrenergic inhibitors
IN
The clinical symptoms associated with BPH result from a combination of dynamic and
mechanical obstructive components. The dynamic component involves smooth muscle tone
in the prostatic urethra and capsule. The mechanical component is the anatomical obstruction
to urine outflow caused by the enlarged prostatic tissue. Medical therapies are being used to
influence these two obstructive components.
D
DE
Alpha blocking agents act on the dynamic component, decreasing the tone of the smooth
muscle in the prostatic urethra and capsule.
In recent years many alpha blockers have been evaluated for the treatment of symptomatic
BPH. Phenoxybenzamine (Dibenzyline),prazosin (Minipress)and terazosin (Hytrin) are the
alpha blockers most widely investigated.
Recent concern over the carcinogenicity,frequency and severity of other effects (such as
dizziness and asthenia) from phenoxybenzamine led to the clinical study of the alpha blocker,
prazosin. 62 Prazosin appears to be equally effectivebut associated with fewer side effects. 63 A
disadvantage of prazosin is that it is administered twice daily
Controlled trials have reported on the short-term improvements in symptoms and safety with
the use of terazosin in patients with BPH. 62,-54,65
However there is a need for additional long-term controlled studies with a greater number of
patients to fully evaluate the effectsof terazosin in patients with BPH. 62 Similar studies are
required for other alpha1 adrenergic inhibitors. The optimal candidate for this therapy has
yet to be defined.
17
Two studies comparing the efficacy of alpha blockers and surgery found that surgery
produced better results and that some patients might benefit from treatment while awaiting
surgery, although significant side effects may severely restrict its use for this purpose. %h7
In general, alpha blockers are administered in doses similar to or lower than those used to
treat hypertension. However their long-term efficacy is uncertain because prostatic volume is
not decreased and the hyperplastic process may continue. a
Hormone therapy
There is considerable evidence that BPH may be partly androgen (hormone)mediated and
Matzkin and Braf have reviewed the literature. 69 Medical treatment with antiandrogens,
luteinising hormone-releasing hormone agonists and gonadotropin-releasing hormone
analogues have been tested and improvement in urodynamics with objective decrease in
prostate volume has been reported.
RE
A class of drugs being evaluated is 5 alpha reductase inhibitors. These agents interfere with
the conversion of testosterone to dihydrotestosterone, the hormone primarily responsible for
prostatic growth and enlargement, 7o by inhibiting the activity of the enzyme 5 alpha
reductase. This results in decreased serum dihydrotestosterone levels while circulating levels
of testosterone are maintamed.
SC
Finasteride (Proscar)is being evaluated in the treatment of symptomatic BPH in many
centres. 7172 The drug received approval in June 1992 by the FDA for this purpose. 72 Proscar
has recentlybeen granted approval by the Australian Government for marketing in this
country.
IN
The magnitude of the changes in urinary flow is small compared to that achieved with TURP
and some sexual dysfunction is observed at higher doses. The drug relieves symptoms in
about one third of all patients, and only if they continue to take it for six months to a year.
The drug is relatively safe, but does have some side effects: impotence, and decreased libido
occur in about 3 per cent of cases.
As with the alpha blockers, daily long-term administration of these drugs poses problems
with compliance and safety.
DE
Experience with these drugs is still in the early clinical stage and the results of more longterm follow-ups are required to establish efficacy, effectivenessand safety
Phyto-pharmaceuticals
The renewed interest in the medical management of BPH has stimulated the search for
treatment of symptomatic BPH by the use of pharmacological compounds derived from
plants.
However reports of definitive trials in the literature are lacking. 73
D
Stents
Stents are devices inserted in the prostatic urethra to restore and maintain the lumen of the
urethra. Stents were first developed as an alternative to a long- term indwelling catheter to
relievebladder outflow obstruction. With improved technology and methods of insertion, the
indications for the use of stents in the male urethra have increased. 75
Stents are usually inserted under direct vision with a cystoscope under local or regional
anaesthesia m a hospital setting.
18
There are a number of stents available. They may be temporary or permanent and may
consist of either expandable tubular mesh or removable metallic spirals.
Temporary stents are usually spiral in shape and are not intended to become incorporated
into the urinary tract. They are therefore likely to become dislodged, leading to further
retention or incontinence requiring readjustment of the position of the spiral. 75
The use of these stents causes considerable morbidity (for example, migration of the device,
infectionand calcification)and are not intended as an alternative to TURP but for use in the
seriously unfit patient. a 7 u 7
Permanent stents are designed to remain permanently in the urethra and allow
epithelialisation over the surface. They have a tubular mesh design and are inserted under
direct vision with a cystoscope in a 10-12 minute procedure performed after the patient
receives a local or regional anaesthetic.
Results with the use of the metallic mesh stent have been encouraging. 75,7&80 However, the
duration of follow-up is still too short in most studies to draw any firm conclusions.
RE
Although the role of intraprostatic stents in the management of BPH has yet to be clearly
established 81, it has been suggested that they may have a role in 5-10 per cent of the
population with BPH who are not candidates for major surgeqm
SC
Balloon dilation
IN
In prostatic balloon dilation a guide wire is passed through a cystoscopeinto the bladder. The
cystoscopeis then removed and a dilating catheter is passed over the guide wire and the
balloon is inflated using a pressure gauge and a hand-held inflating syringe. The balloon is
inflated usually to 4 atmospheres of pressure for 15 minutes to a size of 90F (30 mm). The
balloon is then withdrawn. An indwelling urethral catheter is introduced and may be kept in
place for 3-7 days. It is removed in an outpatient visit.
DE
A physician panel assembled by the American Medical Associationconsidered the safety and
effectiveness of balloon dilation for BPH in patients who require treatment. 82 The panel
concluded that balloon dilation of the prostate is safe but the efficacy of the technique is
unproven. Subsequent studies have failed to resolve the controversy regarding the efficacy of
this technique. 83-85
A review of literature by Perez-Castro et al. concluded that neither symptomatic nor
objective improvement is obtained in more than two thirds of the cases treated with balloon
dilation and that it is not maintained even for a year in more than half the cases.
High intensity focused ultrasound (HIFU)
D
A Canadian assessment of the technology in 1993concluded that as the limited number and
the quality of the studies do not permit an evaluation of its effectiveness, it must be
considered as a technology in the experimental stage of its development.
In this procedure a tramrectal probe provides ultrasound both for imaging and heating
tissue. 87 The focused energy heats the targeted tissue to 80°C-90°C. This causes coagulative
necrosis and results in rapid cell death. No results using this technology have yet been
published.
19
Pyrotherapy
In pyrotherapy highly focused ultrasound waves generated from a transducer outside the
body are used to destroy tissue deep within the body An ultrasound imaging system is
included in the treatment head and is used to locate the target tissue and direct the
procedure. Destruction of the tissue is achieved by both a brief intense rise in the local
temperature (>lOO"C) and non-thermal events (acousticcavitation).The patient receives a
series of pulses of 0.1 to 0.5 seconds each. The short pulse duration minimises thermal
damage to adjacent tissue.
The therapy is experimental and results from some human studies have been reported. ~
4
Ultrasonic aspiration
RE
In this technique electrical energy is converted to mechanical motion at the tip of a hollow
titanium cylinder that vibrates longitudinally along its axis at ultra-high frequencies. The
patients are discharged on the second or third postoperative day.
Two reports using the technology have been published. One concluded that it could be used
m sexually active younger men who have bladder outlet obstruction secondary to prostatic
adenoma and not bladder-neck obstruction. The other report concluded that, after six
months, ultrasonic aspiration appeared to be as efficacious as TURF' for the treatment of
bladder outlet obstruction, but with a decreased incidence of retrograde ejaculation. 91
SC
The technology is still in the development stage.
Cryosurgery
IN
Cryosurgery is the use of sub-zero temperature to destroy diseased prostatic tissue and has
been used in the past to treat prostatic cancer. It was not widely accepted because of local
complicationsdue to poorly controlled freezing. 92 Recent developments in this area have
renewed interest in this technique in the treatment of prostatic cancer 93 and in the treatment
of BPH.
DE
The Working Party is not aware of results of trials using this technique in the treatment of
BPH.
Transurethral needle ablation (TUNA)
D
In this procedure radiofrequency energy is delivered directly into the prostate via two sidedeploying needles delivered from a catheter-like device transurethrally About 8-12 lesions
are required for most prostates and treatment is accomplished in one procedure lasting from
2O-40 minutes, on average. Further clinical details are not available at this stage.
The Working Party is not aware of results of trials using this technique in the treatment of
BPH.
20
~
3
~
Issues related to the introduction
of new technologies for the
treatment of BPH
RE
Although surgery remains the standard treatment for BPH, a number of less invasive
techniques are being developed and are starting to occupy a place in the expanding range of
treatments.
The increasing availability of these technologies raises many issues related to patient
assessment, the status of the new procedures, the need for clinical trials, the potential for
increased procedures on an expanded patient base and costs to the health care system.
SC
Evaluation of patients
Many patients with obstructive symptoms are evaluated minimally, and, with the new
treatments becoming available,there is a peed to improve the urological evaluation of the
patient.
IN
Kirk 94 has commented that measuring outcome of treatment for BPH has not previously been
of great interest, and that urologists have been ‘cavalier’in assessing the benefits of TUlW
The situation is no longer so simple because of the availability of alternative treatments. He
states that as well as objective measurements, patient symptoms must be taken into account.
DE
The timing of any decision to intervene is another important issue in the presence of different
treatment options for BPH. The decision of when to intervene is made more difficult when
the entry requirements for the various technologies are not yet well defined.
Best-practice guidelines
D
There appears to be a need to develop best-practice guidelines to determine what constitutes
a successfuloutcome and to assist practitioners to decide which diagnostic tests should be
performed, when intervention should occur and which treatment option to choose. These
guidelines would be of value to the patient as well as to the general practitioner and the
urologist. The Working Party notes that some alternative treatments are already entering the
Australian scene, and that medical therapy is likely to be carried out by general practitioners
as well as urologists. The Working Party therefore believes that best-practice guidelines are
required as a matter of urgency
The Working Party noted that a WHO-sponsored International Consensus Committee 95
recently adopted recommendations on the diagnosis and treatment of BPH which could serve
as a basis for such guidelines in Australia.
21
The development of best-practice guidelines could have cost implications. Equally their
application could avoid unnecessary intervention.
Prostate cancer testing of men with evidence of urinary obstruction
With recent publicity concerning prostate cancer, patients with minimal obstructive
symptoms are more likely to consult their general practitioner to resolve cancer fears. The
investigation for cancer may diagnose asymptomatic disease which would otherwise have
gone untreated. This may have cost implications.
Prostate cancer is very prevalent in the older male population but is rare in men under the
age of 50 years. In men over 50 years of age about 30 per cent 96,97 have histologic evidence of
prostate cancer and m men over 70 years of age about 45 per cent are likely to have cancer of
the prostate.
The development and adoption of best-practice guidelines should provide a means to
standardise the approach to the testing process.
RE
Recommendation 1
SC
The Working Party recommends that best clinical practice guidelines for the diagnosis and
treatment of BPH be drawn up as a matter of urgency with representation from the Royal
Australian College of General Practitioners, the Urological Society of Australasia, and
expertise provided by consumer bodies and health economists. Recent recommendations
adopted by a WHO-sponsored Consensus Committee on BPH could serve as a basis for .
such guidelines in Australia.
Consumer statement
DE
IN
Men need to be aware that BPH is a normal part of ageing and need to be informed about
when symptoms may warrant treatment. More information should be made available to
patients and the community generally regarding alternative approaches to the treatment of
BPH. The Working Party has developed a consumer statement to meet these needs
(Appendix 2).
Recommendation 2
The Working Party recommends that the consumer statement, contained in Appendix 2
providing information on BPH and the options available for its treatment, should be
disseminated widely.
D
Potential for increased numbers of intervention in Australia
Kaplan et al. 98 found that when faced with treatment choices, patients preferred more
conservative treatments, particularly medical therapy, when their symptoms were mild or
moderate. When symptoms progressed however, more invasive treatment was preferred. The
authors commented that although the risks and benefits of therapeutic alternatives should be
an important consideration, urologists need to be aware of the desires of their patients.
22
The Working Party has noted that, with the introduction of minimally invasive therapies such
as laparoscopic cholecystectomyin Australia, the number of procedures has increased by
25 per cent. There is likely to be a similar degree of unmet demand for the treatment of
urinary obstructive symptoms.
The Working Party anticipates that, with the availability of drug treatment for BPH in
Australia, and in the face of anticipated intense media pressure, general practitioners will
find it difficult to resist or discourage treatment of various degrees of urinary obstruction.
Many men with minimal symptoms of urinary obstruction seek professional advice. As a
result of publicity concerning the availability of other less invasive alternatives besides
prostatectomy and watchful waiting, men, who would have otherwise accepted their
symptoms as part of the ageing process, may well seek treatment. This will result in increased
numbers of interventions adding to health care costs.
RE
Treatment cascade
The introduction of less invasive procedures is likely to add to rather than replace existing
therapies. Patients who are anxious to avoid prostate surgery could conceivablybegin an
open-ended course of therapies involving a number of technologies resulting in a cascade of
therapies being used over the patient’s lifetime. After such options patients may still find it
necessary to undergo prostatectomy.
SC
The extent to which this pattern of care might develop is unknown, but the impact on the
health-care system is potentially cost increasing.
Current status of new technologies
IN
Many of the studies evaluating new alternative therapies for BPH have not provided data on
long-term efficacy or compared the new therapy in a prospective, randomised fashion with
an established treatment such as TURF! l3
DE
Surgical procedures are established, with the use of urethral stents being generally limited to
older patients who are in relatively poor condition. All other alternatives are considered
experimentalby the Working Party with some of these technologiesbeing in a more
advanced stage of development, such as the use of lasers, thermotherapy and drugs. While
the results from the use of these three technologiesare promising, they cannot be regarded as
being established.
The arrival of some of these technologies in Australia without adequate evidence of
effectivenessis of concern to the Working Party
D
Since 1989the drug finasteride has been undergoing trials in three centres in Australia on
small numbers of patients, and a more extensive trial of lasers has been in progress since
1991.The use of stents and balloon dilation have been used in trials to lesser degrees.
The Working Party is aware that the introduction of new technologies for the treatment of
BPH in Australia is imminent, making urgent the need for a more rational introduction of
them in Australia.
23
Recommendation 3
The Working Party recommends that the introduction of new technologies for the
treatment of BPH should be managed in such a way that clearly identifies whether they
are established, or the degree to which they are experimental or emerging.
General problems with research in new treatment
options for BPH
The introduction of new alternative treatments for BPH has led to a substantial body of
literature on the subject in urologic journals. However the Working Party believes that the
inadequacies of the studies do not support the routine introduction of these technologiesin
clinical practice.
RE
Problems relate to the early stage of evolution of the technologies, ongoing refinement of the
techniques and the development of treatment protocols in the presence of evolving
technologies.For example, in the case of thermotherapy and lasers, more research is being
camed out on the optimum energy levels required, method of energy delivery and duration
of treatment. In addition, because of lack of diffusion of the technologies, results from studies
emerge from single institutions.
SC
Reports of prospective randomised controlled trials are in the minority and, in general, small
numbers of patients have been involved. As well, in most cases only short-term results have
been reported.
Another difficulty in assessing results of trials in this area is the uncertainty that comparisons
are made with patients with equal levels of obstruction. Further, in some studies, patient
outcomes have allowed them to meet the entry criteria for the same treatment, the
implication perhaps being that the treatment was unsuccessful.
IN
Adequate assessment of the efficacy of the technologies awaits sizeable, prospective
randomised trials with lengthy follow-up of patients.
Need for regulation and clinical trials
DE
D
As many of the technologies becoming available for the treatment of BPH are still
experimental, the Working Party believes that their introduction should be subject to some
control. The Working Party is concerned by recent experience in Australia where one of the
new technologies attracted considerable press coverage. This raised public awareness and
expectations which were enhanced by the technology attracting a Medicare rebate. These
factors together gave the impression that the procedure was an established technique and
fuelled public demand for increased availability of the technique.
The Working Party considers that none of the new technologies used in the treatment of BPH
have had adequate trials, and that they should be clearly labelled as experimental until they
have been subjected to an evaluation process or clinical trials. There is a need therefore for
control to ensure that they are adequately evaluated before use.
Under current arrangements, the regulation of medical devices within Australia is covered by
the Therapeutic Goods Act 1989 (the Act) and its related Regulations. However this Act tends to
deal with medical devices generically and does not cover medical procedural technologies.
The Act therefore does not provide the control over new BPH technologies envisaged by the
Working Party.
24
In addition, it is currently possible to exert some control over the use of these new
technologiesthrough Medicare rebates. The Working Party believes that Medicare rebates
should not be introduced until the technology has been shown to be safe, effective and cost
effective and can be regarded as established.
The Working Party believes that these mechanisms should be strengthened and linked to
ensure adequate evaluation of BPH technologiesbefore they are used clinically Such controls,
however, should not be so restrictive as to stifle medical research and advances in the
treatment of BPH in Australia. Manufacturers of the technology should also be encouraged to
support trials financially.The Working Party believes that all such trials should be
coordinated by government in conjunction with the urological professional bodies.
Although these controls are intended for new technologies associated with the treatment of
BPH, the Working Party recognisesthat similar controls may have wider application to
medical technology generally.
RE
Recommendation 4
The Working Party recommends that as a matter of urgency, AHTAC consider the need
for a mechanism to ensure that new treatment technologies for BPH have had adequate
trials before they are introduced into routine clinical practice, or alternatively that they are
introduced under trial conditions involving urological professional bodies.
Recommendation 5
SC
The Working Party recommends that funding of trials should generally be from
government or industry. Medicare rebates should be available for technologies shown to
be safe, effective and cost effective, and which can be regarded as established. The
Working Party believes that Medicare rebates should also be available for such established
therapies which are being further evaluated within controlled trials.
IN
Funding issues
DE
The way in which medical and hospital services are funded has the potential to influence
practice patterns. Both State and Commonwealth Governments have available a range of
funding options which might affect the treatment of BPH in the future.
Casemix - or diagnosis-related groups @RG) - funding, with its emphasis on efficiencyin
treating each case and maximising the throughput of hospitals, may encourage the
development and uptake of techniques which shorten patients’ length of stay, or lend
themselves to outpatient treatment.
D
Purchaser-provider (or other population-based) funding systems are also under consideration
in a number of jurisdictions. These seek to contain both cost per case and the volume or
number of cases treated, through capped per capita funding to a purchasing agency Such a
funding system would encourage the development of mechanisms to allow only treatment of
appropriate patients. This would be undertaken through better documentation of the need for
intervention in any particular case of BPH and the use of best-practice guidelines.
While responsibility for health services is split between the Commonwealth and State
Governments, it is likely that providers of care would seek to circumvent regulations at one
level by transferring costs to the other level of government, or to private health insurance.
25
This division of responsibilities may also lead to anomalous treatment patterns, as for
example, greater use of uncapped pharmaceutical therapies (a Commonwealth responsibility)
in the face of restricted access to surgical alternatives (largelyavailable through State-funded
public hospitals).
These effects are not unique, of course, to treatments for BPH, but will have an impact on the
introduction and availability of the therapies considered in this report.
Cost considerations
In addition to the uncertainties regarding safety and efficacy of the various methods for BPH,
it is not yet clear how they might compare with regard to their costs to health programs or to
patients, and analysis will need to take account of patient costs and benefits. There will be
major advantages for many individuals in avoiding complicationsof TURF’,even if surgery is
deferred for a relatively limited time.
RE
A cost-effectivenessstudy of the use of lasers in Australia is in progress but results are not yet
available.
SC
Russell and co-workers examined the relative costs of TURP and drugs in the management
of BPH. They commented that an idealised comparison would compare the two options over
13 years, would assume minimal follow-up of the TURP patients, and for simplicity would
assume also no cross-over or failure in the medical group. Given these assumptions, they
calculated that the cost of medical management exceeded that for surgery at six years and
was twice the cost at 13 years.
D
DE
IN
In general, however, it would be difficult to amve at meaningful cost data on the range of
therapeutic alternatives to the treatment of BPH because of their early stage of development
and the absence of information on failure rates, re-treatment rates, lack of data on which
patients would benefit from a particular treatment and what mix of technologies would
prevail.
26
Appendix 1
AHTAC Working Party
Terms of reference
In investigating the clinical treatment of benign prostatic hyperplasia, the Working Party will:
Dr D Waggett
l
Dr T Jackson
l
Mr W Johnson
D
DE
IN
Chair
Member of AHTAC
expertise in biomedical engineering
St Vincent’sHospital, Melbourne
expertise m hospital administration
National Centre for Health Program Evaluation
health economist
Royal Melbourne Hospital
practising urologist
Flinders Medical Centre
practising urologist
La Trobe University
nominee of Consumers’ Health Forum
l
Dr D Campbell
SC
RE
assess the current effectivenessof microwave thermotherapy;
assess the current availability and effectivenessof other alternatives to surgery;
assess the potential role of microwave thermotherapy, and other alternatives to surgery
within the Australian health care setting;
ascertain the cost and estimate the cost-effectiveness, including any cost savings to the
Australian health care system, resulting from the introduction of microwave
thermotherapy or other alternatives to surgery;
determine issues which need to be considered by governments, the health professions
and the community, in the introduction of microwave thermotherapy or other
alternatives to surgery; and
recommend the approach and direction that Australian governments should take with
the introduction of microwave thermotherapy or other alternatives to surgery.
Members of the Working Party during preparation of this report were:
l
Prof V Marshal1
l
A/Professor E Willis
l
27
Appendix 2
Consumer statement on the treatment of benign prostatic
hyperplasia (BPH)
Non-cancerous enlargement of the prostate
(BenignProstatic Hyperplasia)
what are the options?
Changes in the prostate over time
RE
The prostate gland produces most of the fluid in semen. It is just below the bladder, and
surrounds part of the urethra (the tube passing u m e from the bladder through the penis).
The prostate maintains a constant size from puberty to about 45-50 years of age. At that
point, it should begin to progressively decreasein size. However, for about half or more of
men, the prostate enlargesinstead. This non-cancerous enlargementis called Benign Prostatic
Hyperplasia (BPH).
SC
BPH seems to be a process of age and the normal function of the testes, and has not been
associated with any lifestyle or risk factors. The condition can worsen to the point where
seriousurinary complicationsmay develop, but that is unusual.
What are the symptoms?
IN
An enlargingprostate can put pressure on the urethra, and so obstruct the flow of urine. The
symptoms of BPH are called ’prostatism’, and include:
l
DE
diminution in the calibre and force of the stream of urine;
hesitancy in beginning to urinate;
an inability to end the flow abruptly, with dribbling afterwards; and
a sensation of incomplete emptying of the bladder.
Occasionally men with BPH can suffer from k-ineretention. Mostly though, men seek
medical advice if they find they need to urinate too often at night. It is important to
distinguish between BPH and other problems, such as urinary tract conditionswhich involve
pain or urgency and frequency of urination. Accurate diagnosis is therefore important,
including ruling out prostate cancer.
l
l
l
D
There is a lot of variation in men’s experiencesof BPH, and the difficultiesit causes them. It
has been estimated that this conditiongenerally improves for about 20 per cent of men, and
gets worse for another 20 per cent, with the severity of problems over the years varying for
the others.
What is the usual treatment?
Treatment decisions depend largely on individual men’s preferences and circumstances.The
most appropriate action generally is to monitor BPH carefully and only treat it more actively
if the conditionbecomes very problematic or complications develop. Current treatment,
28
while quite effective, is invasive and can cause other problems with urinary and sexual
function. Newer treatmentswhich are less invasive and which minimise these worrying side
effects are being explored,but they are still experimental.
At the moment, the main treatment offered for BPH is surgery40 reduce the prostate. A
procedure known as a TURP (transurethral resection of the prostate) has been used very
commonly for years. A TURP involves using a endoscope to view and reach the prostate
through the urethra, so that the surgery can be done without any open or external incisions.
It provides a fair degree of relief for most of the men who undergo it, although some need reoperationin subsequent years.
When the prostate is smaller, a TUIP (transurethral incision of the prostate) may be possible.
Another endoscopicprocedure, this form of surgery has been associated with a much lower
rate of post-operative problems than the TURP.
Neither endoscopicprocedureswill always be possible if the prostate is particularlylarge. In
these relatively rare circumstances, an 'open prostatectomy' may be needed.
RE
While quite large numbers of men report problems with incontinenceor disruption to sexual
function after prostate surgery, this may be partly due to the fact that it is often undertaken m
the men experiencingthe greatest difficulties-or avoided till the condition has become
complicated.Other than 'watchful waiting', surgery is still the treatment most confidently
recommendedby health authorities.
SC
What are the new treatments?
IN
The Australian Health TechnologyAdvisory Committee (AHTAC)believes that some new
techniques may prove to be useful, and has recommended that severalbe evaluated in
clinical trials. However, there is not enough evidence about the safety and effectivenessof
these treatments for any to be recommended as yet. While some may eventually prove to be
valuable, others may turn out to be less effective and/or more harmful than current forms of
care.
The new treatmentsbeing explored use a variety of techniques, including:
DE
thermal energy sources such as lasers, ultrasound, and microwaves to remove the excess
tissue;
mechanical techniques such as balloon dilation (using a ballooningdevice to enlarge the
urethra) and stents (artificialtubes) to overcome the obstruction;
drugs and hormones to reduce the severity of the symptoms as well as the obstruction.
More detailed information on these techniques is availablem a report from AHTAC. With the
exception of stents, which may be needed for some older men who need treatment but cannot
have surgery, all the new methods are regarded by AHTAC as experimentalonly.
l
l
l
D
There is some concern that many men who want to avoid surgery may find themselves t&ing
several of these therapies to find relief from the symptoms of urinary obstruction -including
long-term daily usage of drugs whose ultimate side effectshave not been adequately studied.
Surgery may still be the only effectiveform of treatment.
Until further evidence is availableto firmly support or reject alternative treatments, AHTAC
concluded that 'watchful waiting', with surgery when necessary, remains the best treatment
for BPH. Men should be fully informed of the status of any alternativesoffered to them.
29
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2
3
5
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11
13
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17
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7
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