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 Introduction
For decades, Transurethral
Resection of the Prostate (TURP) was the
undisputed gold standard therapy for
treatment of Lower Urinary Tract
Symptoms (LUTS) due to benign prostatic
hyperplasia (BPH). Within the past 15
years, the role of TURP has been
increasingly challenged by the
development of medical therapies and
Minimally Invasive Treatments (MITs).
The aim of the present review is to
provide updated information regarding
the current role of MITs for LUTS/BPH.
Key Words: Prostate, benign disease,
hyperplasia, treatment, minimally
invasive
Classification of MITs
MITs
could be classified into 5 categories:
1. Thermal-Based Therapies.
2. Laser
Therapies.
3. Transurethral Vaporization
of the Prostate (TUVP).
4. Balloon & Stents.
5. Chemoablation.
1. Thermal-Based Therapies
Thermal-based therapies use high
temperatures to induce a coagulation
necrosis within the prostate. A
thermal-based therapy that achieves
temperatures below 450C is referred to
as hyperthermia and treatment
temperatures above 450C are referred to
as thermotherapy. There are 2 types of
thermotherapy: low-energy thermotherapy
with temperature 45-600C and high
-energy thermotherapy with temperature >
600C.
Classification of Thermal-Based Therapies
1- Transurethral
and transrectal hyperthemia.
2-
Low-Energy Transurethral Microwave
Thermotherapy (LE-TUMT).
3- High-energy
transurethral microwave thermotherapy
(HE-TUMT).
4- Water -Induced
Thermotherapy (WIT).
5- High -Intensity
Focused Ultrasound (HIFU).
6-
Transurethral Needle Ablation (TUNA).
1.1. Transurethral and Transrectal Hyperthermia
Via a al or
transurethral route, therapeutic
temperature of < 45 0C are generated by
microwaves. Randomized Clinical Trials (RCTs)
showed that hyperthermia induces only a
transient improvement of symptoms with
no proof of long-term efficacy.
Therefore, this technique is not
recommended by the European Association
of Urology (EAU) and the American
Urological Association (AUA) guidelines
(1,2). This technique is considered
obsolete for treatment of BPH (1,2).
1.2. Low-Energy Transurethral Microwave Thermotherapy (LE-TUMT)
Via a
transurethral route, microwave is used
to increase the temperature of the
prostate to 45 - 60 0C. Short-term
results of this technique are good.
However, long-term data are
disappointing with a failure rate
between 25% to 70% (3). Due to these
poor long-term results, LE-TUMT has been
abandoned.
1.3. High-Energy Transurethral Microwave Thermotherapy (HE-TUMT)
The HE-ce consists of
a module and a treatment catheter. The
module contains microwave generator,
temperature sensor and fluid channels
for cooling of the prostatic urethra.
The microwave energy is delivered to
increase the temperature within the
prostate > 60 0C, thus inducing a
coagulation necrosis.
Randomized
Clinical Trials (RCTs) comparing HE-TUMT
versus TURP showed a comparable
improvement in symptom score (63% for
TUMT Vs 74% for TURP). However, the
improvement in the maximum flow rate (Q
max) and the reduction in post-voiding
residual urine (PVR) were significantly
higher with TURP (Q max 53% Vs 128%; PVR
32% Vs 78% for TUMT and TURP,
respectively (4).
HE-TUMT has the
advantages of being done under local
anesthesia as an outpatient procedure
with minimal postoperative morbidity.
However, it has the disadvantages of
prolonged catheterization (2-4 weeks)
and high re-treatment rate (5-15% at one
year).
The guidelines of EAU and AUA
stated that HE-TUMT should be reserved
for patients who prefer to avoid surgery
or who no longer respond favorably to
medication (1,2).
1.4. Water-Induced therapy (WIT)
WIT is carried out under
local anesthesia via an 18 F WIT
catheter which consists of a treatment
balloon inflatable to 50 F within which
heated water circulates during therapy
and an air inflatable positioning
balloon.
Muschter et al performed a
single-arm multicenter trial on
125 patients (5). At 12 months, the
International Prostate Symptom Score (IPSS)
improved by a median of 12.5 points and
Q max by 6.4 ml/s. Serious adverse
events are infrequent.
The EAU and AUA guidelines consider WIT
to be an investigational procedure,
which should not be offered outside the
framework of clinical trials (1,2).
1.5. High Intensity Focused Ultrasound (HIFU)
HIFU is carried out under
spinal or general anesthesia via a
transrectal ultrasound transducer which
increases the temperature of the
prostate to 80-200 0C, thus inducing
coagulation necrosis.
Madersbacher et al studied the long-term outcome of 80 patients followed
for a mean of 41 months (6). Within 4
years, 44% of patients underwent TURP.
EAU and AUA guidelines consider HIFU to
be an investigational procedure for
indication BPH, which should not be
offered outside the framework of
clinical trials (1,2).
1.6. Transurethral Needle Ablation (TUNA)
TUNA delivers low radio
frequency energy directly into selected
areas of the prostate through a catheter
equipped with adjustable needles, thus
producing a coagulation necrosis while
sparing the urethral mucosa. Ablation is
achieved when the needles reach
temperatures of 80-100 0C. TUNA can be
performed under local anesthesia
although it has a higher requirement for
analgesia and sedation than does TUMT.
Bruskewitz et. al, randomized 121
patients to TUNA or TURP(7). While
improvements of the bother score was
similar in both groups, changes of
symptoms and Q max were higher in TURP
arm (7). Zlotta et al reported on the
outcome of TUNA with a follow-up of up
to 5 years in 3 centers (8). A total of
23% of patients required additional BPH
treatment after a mean of 63 months (8).
The EAU and AUA guidelines stated that due to a significant treatment
failure rate, TUNA is not recommended as
a first line treatment for LUTS/BPH
(1,2).
2. Laser Therapies
Laser energy can be used to produce
coagulation necrosis, vaporization of
tissue or resection of tissue. The most
commonly used types of laser therapies
include:
1- Visual Laser Ablation (VLAP).
2- Interstitial Laser Coagulation (ILC).
3- Holmium Laser Resection (HoLR).
2.1. Visual Laser Ablation (VLAP)
Nd: YAG laser is used in either
non-contact technique to induce
coagulation necrosis or in contact
technique to produce immediate
vaporization of tissue. RCTs comparing
VLAP Vs TURP showed that both arms
produces a comparable improvement in
IPSS (63% Vs 71%) and increase in Q max
(93% Vs 109%) for VLAP and TURP,
respectively (9). Moreover, VLAP has the
advantages of less bleeding and less TUR
syndrome. However, the non-contact
technique has the limitation of
prolonged period of catheterization. The
best results were obtained with small
and moderate sized prostates.
Long-term studies comparing VLAP Vs TURP
at 3 and 5 years showed that the
improvement of symptom score was similar
but VLAP had a higher re-treatment rate
(10).
The EAU and AUA guidelines stated that
VLAP is not recommended as first line
surgical treatment for LUTS/BPH. It may
have a role in high-risk patients.
2.2. Interstitial Laser Coagulation (ILC)
Under cystoscopic control,
laser fibers are directly introduced
into the prostate. This technique gives
fewer irritative symptoms because the
urethral mucosa is spared and prostate
tissue is resorbed by the body rather
than sloughed.
RCTs comparing ILC Vs
TURP showed comparable improvements of
symptoms, but improvement in Q max and
PVR were less after ILC (11). The
re-treatment rate is 5-15% at 12 months.
The EAU guidelines stated that ILC is
not recommended as a first-line surgical
treatment of LUTS/BPH (1). It may have a
role in the treatment of high risk
patients (1). The AUA guidelines stated
that there is inadequate evidence to
support inclusion of ILC as treatment
option of LUTS/BPH (2).
2.3. Holmium-Laser Resection (HoLR)
With HoLR the prostatic adenoma is mobilized and
then either morcillated or resected
using the mushroom technique.
Gilling et
al compared HoLR to TURP in 120 men
followed for 12 months (12). Both
treatments resulted in significant and
comparable improvements in symptom
score, quality of life and Q max.
Operating time was significantly longer
during HoLR, catheter time and hospital
stays were shorter after HoLR (12).
Intraoperative morbidity was lower after
HoLR. HoLR can be performed even in men
with large prostates as documented by
Kuntz and Lehrich who randomized 120 men
with prostates > 100 g to HoLR or open
prostatectomy (13). Improvement of
symptoms and Q max were comparable in
both groups. Surgical time was longer
with HoLR. Hospital stay and
catheterization time were significantly
shorter after HoLR (13). Blood
transfusions were required in 13% after
open prostatectomy as compared to 0%
after HoLR.
The EAU guidelines stated
that HoLR is a promising new technique
with outcomes in the same range as those
of TURP (1). According to the AUA
guidelines, HoLR is an option for
patients seeking an alternative method
of resection or enucleation of the
prostate in medical centers where the
procedure is available (2).
3. Transurethral Vaporization of the Prostate (TUVP)
TUVP uses a modified transurethral
equipment that delivers uninterrupted
high electrical energy causing
vaporization of tissue. Thermal damage
to surrounding structures, even at a 300
W setting, does not seem to be a major
problem. The major disadvantage of TUVP
is that the clinical efficacy of the
electrode rapidly decreases as tissue
desiccates. The total energy used during
TUVP is 8-10 fold higher than that of
the conventional TURP. Furthermore, the
electrode must be activated for
substantially longer time during TUVP.
RCTs comparing TUVP Vs TURP showed
comparable improvement in symptom score
and Q max in both arms. The risk of
bleeding and of TUR syndrome is lower
after TUVP. These data of RCTs suggest
that the clinical efficacy of TUVP seems
to be comparable to conventional TURP at
least for patients with small prostates
(14). Moreover, a recent study by
Hammadeh et al reported results of TUVP
similar to TURP after 5 years of
follow-up (15).
The TUVP is not mentioned in the EAU
guidelines as it is considered as a
modification of conventional TURP than
an MIT (1). The AUA guidelines state
that long-term comparative trials are
needed to determine if TUVP is superior
to standard TURP (2).
4. Balloon and Stents
4.1. Balloon dilatation
Balloon
dilatation is not recommended for
treatment of ng to the
AUA guidelines (2) and not mentioned any
more in the EAU guidelines (1). This
technique is considered obsolete for
this indication.
4.2. Prostatic Stents
Prostatic stents are not mentioned any
more in the EAU guidelines (1). The AUA
guidelines stated that because of the
significant associated complications,
stents are indicated only for high-risk
patients with short life expectancy
suffering from urinary retention (2)
5. Chemoablation
This technique involves
transurethral injection of abolute
alcohol into the prostate leading to
coagulation necrosis. A small
single-centers studies have reported
encouraging results, although
significant side effects such as bladder
necrosis requiring surgical intervention
have been reported as well (16).
Due to
its recent development, chemoablation is
not mentioned in the EAU and AUA
guidelines (1,2).
Discussion: MITs Vs TURP
In this part of the review a global
comparison will be made between MITs and
TURP regarding anesthesia, intra-and
post-operative complications, sexual
dysfunction, learning curve, clinical
efficacy, durability of the clinical
response and anatomical limitations.
* Anesthesia
One attracting aspect of MITs
is the avoidance of anesthesia thus
being able to treat high-risk patients
unfit for general anesthesia or to be
performed on a purely outpatient basis
(17). However, only TUMT and WIT can be
reliably performed under local
anesthesia. TUNA and ILC usually require
some form of intravenous sedation. More
invasive MITs, such as TUVP and various
laser approaches require general or
spinal anesthesia similar to
conventional TURP (17).
* Intra-and postoperative complications
Compared to TURP, MITs have the advantage of less
intraoperative complications in the form
of bleeding and TUR syndrome. For this
reason, MITs can be safely performed in
patients with bleeding disorders or
under warfarin therapy (17). On the
other hand, the incidence of
postoperative complications is
significantly higher with MITs.
Particularly with non-ablative
techniques, major complications include
prolonged catheter time (up to 6 weeks)
and high degree of postoperative dysuria.
* Sexual dysfunction
Impairment of
erectile function was not observed after MITs (17). The long-standing controversy
on erectile dysfunction after TURP was
classified by the Veterans Affairs
Cooperative Study Group comparing TURP
with watchful waiting (18). After a mean
follow-up of 2.8 years, the proportion
of patients deteriorating their sexual
performance was identical in both arms,
i.e. 19% after TURP and 21% after
watchful waiting (18).
The incidence of
retrograde ejaculation after TURP
depends on the degree of bladder neck
resection and in a recent meta-analysis
this incidence was 65% (19). The
incidence of retrograde ejaculation
after MITs depends on the invasiveness
of the procedure and if preservation of
the bladder neck is obtained. Antegrade
ejaculation is preserved in up to 70%
following TUMT, TUNA, ILC and WIT.
Nevertheless, more invasive MITs, such
as TUVP, VLAP or HoLR result in
incidence of retrograde ejaculation
comparable to TURP.
* Learning curve
TURP is considered a rather difficult
surgical procedure requiring a
substantial big number of cases to
become familiar with it. An attracting
aspect of many MITs is the short
learning curve. Procedures like TUMT,
TUNA, ILC, VLAP and TUVP require few
cases to achieve an adequate skill,
particularly for urologists familiar
with endoscopic procedures and TURP.
Selectively, HoLR has a long learning
curve and requires a big number of cases
to be familiar with it.
* Clinical efficacy
Conventional TURP is still the
"gold standard". Although improvements
of symptoms following MITs are generally
in the range of TURP, changes of
objective and urodynamic parameters are
more profound after TURP. In general,
there is a close correlation between the
degree of invasiveness of a MIT and the
clinical efficacy. Procedures like TUMT,
TUNA or ILC lead only to moderate
improvements of Q max and PVR. More
invasive procedures, such as TUVP and
HoLR lead to changes comparable to
conventional TURP.
* Durability of clinical response
One of the crucial
issues of any therapy of LUTS/BPH is the
durability of the clinical response. The
rate of secondary intervention needed is
the essential variable for evaluating
the long-term efficacy of procedures
aimed at relieving bladder outflow
obstruction. In a recent meta-analysis
of 29 RCTs, the rate of secondary
intervention after TURP was 2.6% with a
mean follow-up of 16 months (19). The
need for secondary intervention is
substantially higher after MITs.
* Anatomical Limitations
A drawback of many MITs is the fact
that anatomical limitations may hinder
their general application, in particular
regarding prostate volume and shape. For
example, larger prostate cannot be
reliably treated by VLAP, HIFU and TUVP.
Patients with large median lobes are
generally considered not good candidates
for TUMT, TUNA and HIFU. Moreover, HIFU
cannot be performed in men with
prostates with dense calcifications
because of the possibility of tissue
cavitation (17). The advantage of TURP
to MIT is the tissue availability for
histopathology .
Conclusions
Many early MITs such as balloon
dilatation and hyperthermia have been
abandoned despite initial enthusiastic
reports. The clinically most effective
MITs are TUVP (particularly for small
prostates) and HLoR. Both procedures,
however, require anesthesia (similar to
conventional TURP) and can be considered
as modifications of TURP. Any MIT not
recommended as an established method of
treatment for LUTS/BPH by the EAU and
AUA guidelines should not be used
outside the context of clinical trials.
References
Other
Topics:
Review Article # 1
- Poisoning with Organophosphorus Compounds (OPC): Mythology vs. Reality
Review Article # 3
- Insight into the New Changes in European Resuseition Council Guidelines for
Adult Resuscitation (2005)
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