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Sonablate®-500: Transrectal high-intensity focused ultrasound for the treatment of prostate cancer


Abstract and Figures

Prostate cancer (PCa) is the most common cancer in men and the second leading cause of death from malignancy in the UK. The number of men diagnosed with PCa is increasing, due in part to an increased willingness of men to visit their family doctors with lower urinary tract symptoms, and also a willingness of physicians to test for it. As the demographic of men diagnosed with PCa becomes younger and better informed, so the demand for a less-invasive alternative to standard therapies becomes greater. The Sonablate-500 is one of only two high-intensity focused ultrasound (HIFU) devices commercially available to treat PCa. HIFU is an attractive treatment option as it is the only form of therapy that neither involves direct instrumentation of the prostate nor ionizing radiation. This article describes the unique features of both the Sonablate-500 system hardware and software, and the outcome data from this device in the context of current standard therapies. Finally, a view into the future attempts to outline where this technology is heading and how a paradigm shift in the way that PCa is considered may make HIFU even more relevant.
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Device Profile
10.1586/17434440.3.6.717 © 2006 Future Drugs Ltd ISSN 1743-4440
Sonablate®-500: transrectal
high-intensity focused
ultrasound for the treatment of
prostate cancer
Rowland Illing and Mark Emberton
Author for correspondence
The Clinical Effectiveness Unit,
The Royal College of Surgeons of
England, 35/43 Lincolns Inn
Fields, London, WC2A 3PE, UK
Tel.: +44 207 869 6600
Fax: +44 207 869 6644
ablation, cancer, focused
ultrasound, HIFU, prostate,
visually directed
Prostate cancer (PCa) is the most common cancer in men and the second leading cause
of death from malignancy in the UK. The number of men diagnosed with PCa is increasing,
due in part to an increased willingness of men to visit their family doctors with lower urinary
tract symptoms, and also a willingness of physicians to test for it. As the demographic of
men diagnosed with PCa becomes younger and better informed, so the demand for a
less-invasive alternative to standard therapies becomes greater. The Sonablate
-500 is
one of only two high-intensity focused ultrasound (HIFU) devices commercially available
to treat PCa. HIFU is an attractive treatment option as it is the only form of therapy that
neither involves direct instrumentation of the prostate nor ionizing radiation. This article
describes the unique features of both the Sonablate
-500 system hardware and software,
and the outcome data from this device in the context of current standard therapies. Finally,
a view into the future attempts to outline where this technology is heading and how a
paradigm shift in the way that PCa is considered may make HIFU even more relevant.
Expert Rev. Med. Devices 3(6), 717–729 (2006)
Prostate cancer (PCa) is the most common
cancer in men and the second leading cause of
death from malignancy in the UK [1]. The
mainstay of treatment remains radical surgery
or radiation therapy; however, there are several
minimally invasive treatments now under eval-
uation that may prove to be of equivalent
oncological effectiveness in the long term [2].
The most common radical therapy – surgi-
cal excision of the prostate – has been shown
to have a modest impact on disease-specific
survival in men with cancer confined to the
prostate [3]. Over a 10 year period, surgery
offered a 5% increase in survival over observa-
tion alone (decreasing the disease specific mor-
tality from 14 to 9%). Consider also that the
side effects of the most common radical treat-
ments are high – they include amongst others
deterioration in urinary, sexual and bowel
function [4,5]. The profile and probability of
these harmful outcomes depend to a large
extent on the type of radical treatment, but all
occur as a consequence of damaging tissue or
structures that exist outside the prostate gland
– the external sphincter, the neurovascular
bundles and the rectal mucosa, respectively.
Refinements in the traditional radical therapies
(conformal or intensity modulated radiation
therapy on the one hand vs laparoscopic or
robotic radical prostatectomy on the other)
have had little impact on the key treatment
related morbidities [6,7].
The desirable attributes for a new technology
in this field have been outlined previously
(BOX 1) [8]. What is required is a truly confor-
mal, noninvasive means of performing radical
treatment for PCa; reducing the side-effect pro-
file while maintaining oncological efficacy.
Transrectal high-intensity focused ultrasound
(HIFU) has the potential to meet these require-
ments [9]. HIFU relies on the physical proper-
ties of ultrasound within tissues. For therapeu-
tic purposes ultrasound energy is focused by
either an acoustic lens, bowl-shaped transducer
Overview of the market
How the device works
Expert commentary
Future developments
Five-year view
Key issues
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Illing & Emberton
Expert Rev. Med. Devices 3(6), (2006)
or electronic phased array. As ultrasound propagates through tis-
sue, zones of high and low pressure are created. When the
energy density (in W/cm2) at the focus is sufficiently high (dur-
ing the high pressure phase), tissue damage (protein denatura-
tion) may occur as a result of thermal coagulation necrosis,
whereas acoustic cavitation may occur in the pressure nadirs.
Tissue water boiling may occur as a result of both the heating
and cavitation effects [10]. As shown in FIGURE 1, the volume of
a HIFU generated lesion at the focal point is small (typically
10–12 mm long by 3 mm wide, in a cigar shape orientated
along the long axis of the beam). To ablate a continuous vol-
ume of tissue, individual HIFU lesions are placed overlapping
next to each other in order to provide a continuous zone of
necrosis. HIFU has been used on an experimental and clinical
basis as noninvasive therapy for clinically localized PCa since
the 1990s [9].
Overview of the market
The market for devices used in the treatment of organ-confined
PCa is expanding. The number of men diagnosed with PCa is
increasing, due in part to an increased willingness of men to
visit their family doctors with lower urinary tract symptoms,
and also a willingness of physicians to test for it [11]. In 2005,
approximately 232,000 new cases of PCa were diagnosed in the
USA and approximately 30,000 deaths from PCa occurred [12].
It is estimated that the lifetime risk for a man diagnosed with
PCa is approximately 40%, and this realization has led to a
great increase in the use of screening tests. In the state of
Ontario, Canada the use of prostate specific antigen (PSA) test-
ing has increased by 388% between 1996 and 2000, and in some
American states over 40% of men over the age of 40 now
undergo PSA screening [13]. Despite there being concerns over
the use of PSA as a screening tool, it is a fact that as men become
more informed, the detection rates of small, early-stage PCa will
continue to rise. That having been said, there is now a movement
by some oncologists and urologists not to immediately treat all
early-stage PCa, but rather place these patients under ‘active
surveillance’ until there is definite evidence of disease
progression [14].
How the device works
The Sonablate®-500 (SB-500; Focus Surgery, Inc., IN, USA)
ablates the prostate via a probe inserted into the rectum while
the patient is anaesthetized. The probe contains elements that
both image and treat the prostate noninvasively through the
intact rectal wall.
The SB-500 system as shown in FIGURE 2A consists of a con-
sole, printer, flat screen monitor and a transrectal probe
incorporating two transducers of different focal lengths.
Main accessories include an articulated probe arm and a
chiller unit.
The mobile operator’s console consists of a main unit hous-
ing the ultrasound generator, flat panel 17” Active Matrix TFT-
LCD color monitor, keyboard with integral mouse buttons and
trackball, and a housing for a printer.
The SB-500 probe consists of probe tip, front housing,
probe body and probe cable connector (FIGURE 2B). It is made
from polyurethane; is just under 60 cm in length, has a tip
diameter of 3.45 cm, a neck diameter of 1.8 cm and weighs
3.2 kg. The probe tip contains two ultrasound transducers of
differing focal lengths mounted back-to-back (FIGURE 2C). The
transducers are made from a proprietary piezoceramic and
have the capability to both image and deliver HIFU treatment
pulses through the acoustic window opening in the probe tip.
The transducer moves in a longitudinal direction to provide
saggital images of the prostate and oscillates in the transverse
plane for transverse (sector) imaging. An elastomeric sheath
(latex and latex-free versions available) surrounds the probe
tip, and is secured to the probe tip via two O-rings. This
allows degassed and chilled water to circulate around the
transducer inside the probe tip, providing the necessary
coupling of the ultrasound energy for imaging and therapy to
the patient, as well as rectal wall cooling. The probe body,
Box 1. Desirable attributes of a new tissue ablation
technology for prostate cancer.
Administered with the patient under local anesthesia
Real-time monitoring of treatment
Excellent oncological efficacy (destruction of all
prostate cancer)
Minimal inflammatory response
No adverse effect on pretreatment erectile function
No adverse effect on pretreatment urinary continence
No injury to adjacent structures (rectum, bladder)
•Low cost
Outpatient treatment
Taken from [8].
Figure 1. Typical high-intensity focused ultrasound beam. Adapted with
permission from Focus Surgery, Inc. (IN, USA).
Focus Surgery, Inc.
2000 W/cm
10 W/cm
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connected to the tip by the front housing, contains the inline
rotary motor for moving the transducers for transverse
imaging, and a linear actuator for saggital movement.
The standard probe produced by Focus Surgery incorpo-
rates transducers with focal lengths of 30 and 40 mm, and a
90° treatment window (FIGURE 2D); however, probes are now
available with the longer focal length of 45 or 50 mm to
accommodate larger glands.
The articulated arm is a universal probe holder that can be
attached to most operating tables. It has a simple locking mech-
anism to tighten three integral joints and a separate ring
through which the probe is inserted, allowing probe
positioning flexibility. This arrangement allows treatments with
the SB-500 system to be performed in any setting where an
operating table is available.
The Sonachill™ device circulates degassed water through the
probe to cool the rectal wall and HIFU transducer. It is
connected to the back panel of the SB-500 console via a solid
connector cable and to the probe with hollow connecting
tubes. The solid connection provides the power supply to the
Sonachill and temperature feedback to the system while the
hollow tubes allow water circulation.
Figure 2. (A) The Sonablate®-500 (SB-500) mobile console, articulated Probe Arm, Probe, and Sonachill™ cooling unit. (B) The SB-500 probe (here seen held by the
articulating probe arm). (C) Cutaway section through the probe tip showing the arrangement of the two transducers with different focal lengths for treating tissue
at different depths. (D) The SB-500 Probe features a wide 90° treatment field; the next generation of probes feature the choice of longer focal length transducers.
Figure 3. Tabbed pages on the user interface.
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Illing & Emberton
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The three main components of the chiller are:
Liquid-to-air active cooling unit
•Peristaltic pump
•Water reservoir
An important function of the Sonachill is to remove the
closed system of any air bubbles before starting the procedure.
The water reservoir has a connector on the sidewall, which is
connected to a syringe. This is used to adjust the volume of
the sheath by pushing water in or removing it, inflating and
deflating, respectively. Fine adjustment between the trans-
ducer’s focal zones and the treatment regions is achieved using
this syringe.
The SB-500 records treatment images either to a digital
graphic printer or to the systems hard disk. This allows the
physician to record (and later review) the entire
HIFU treatment.
Patient selection & preparation
A CE mark has been awarded for the treatment of patients
with primary PCa or recurrent PCa following prior therapy.
Exclusion criteria include: evidence of metastatic disease;
previous rectal surgery (excluding surgery for hemorrhoids);
anal stenosis; metal implants or stents in the urethra; history
of prostatitis in the last 6 months; or active urinary tract
infection. Relative contraindications include: bleeding
disorders; extensive microcalcification within the prostate;
gland calcification greater than 1 cm in diameter; gland size
greater than 40 ml or an antero–posterior diameter of greater
than 4.0 cm when using a probe with maximum focal length
of 5 cm.
Prior to therapy, patients are prepared with two phosphate
enemas to empty the rectum. They then undergo
spinal/epidural or general anesthesia and are placed in the
lithotomy position. Prior to treatment a suprapubic catheter
(SPC) may be inserted under direct vision using a
cystoscope. The anal sphincter is gently dilated and the
treatment probe is introduced with a covering of ultrasound
gel to couple it to the rectal mucosa and then held in posi-
tion by the articulated arm attached to the theatre table. A
16ch Foley urethral catheter is inserted under sterile tech-
nique, and a 10 ml balloon can be inflated to allow accurate
visualization of the bladder neck and median saggital plane,
if required.
Figure 4. Screenshot from the Sonablate®-500 during therapy showing treatment of the preplanned anterior zone of the prostate.
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The custom SB-500 application program runs on a Windows
XP™ platform. It is written in C2+ and Java, uses Snag-It software
to manage treatment recording and Sonablate Information
Management System (SiMS™) to manage SB-500 access control.
The SB-500 HIFU Prostate Therapy software allows ultrasonic
imaging of the prostate in both transverse and saggital planes
(with 3D reconstruction), on-screen treatment planning and
HIFU therapy within user-defined treatment zones. At start-up
an automatic system check commences which verifies the circuits
and treatment cycle properties. Simple image and therapy verifica-
tion functionality tests can be performed by the user or service
personnel to verify proper unit function as part of a regular
maintenance schedule, or after unit transportation to a new site.
The operator interfaces with the software through multiple
tabbed pages – Prepare, Image, Plan, Volume and Therapy
(FIGURE 3). Axial and saggital images are taken through the
prostate using the transducer in the imaging mode. Treatment
planning is carried out using proprietary software that allows
the prostate to be divided into treatment regions – anterior,
middle and posterior, on both right and left sides if necessary
(FIGURE 4). A specific program [15] allows detection of the
periprostatic vessels, thought to be related to the neurovascular
bundles. This can be used should the physician wish to attempt
to perform a ‘nerve-sparing’ treatment to preserve erectile func-
tion (FIGURE 5). The software directs the transducer to move
automatically in the region prescribed by the physician during
the treatment plan mode so that the acoustic focus is moved
sequentially through each point in the treatment plan. Each
acoustic pulse ablates a volume of 3×3×10–12 mm by heat-
ing the tissue to 80–98oC almost instantaneously [16], and indi-
vidual lesions overlap slightly to ‘paint out’ the entire volume,
using a combination of 3 s exposures (‘on’) time and 3 or 6 s
pauses (‘off’) time, during which real-time visualization of the
gland takes place. The longer focal length probe is used to treat
anterior and the mid-part of the gland, and the 3 cm probe
used to treat the anterior block.
Figure 5. The neurovascular bundle identification screen.
Box 2. Features unique to the Sonablate®-500.
User directed power input
Neurovascular bundle identification (FIGURE 5)
3D image reconstruction (FIGURE 6B)
Intraprocedure therapy plan modification using the
Stack feature
Reflectivity index measurement monitoring
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Illing & Emberton
Expert Rev. Med. Devices 3(6), (2006)
As the software is semi-automated, however, control over the
amount of energy that is administered to the prostate remains
under the control of the user. A method of treatment termed
‘visually directed’ HIFU has been suggested, the early results of
which show it to be potentially more efficacious than other
techniques and systems currently available [17]. Visually directed
HIFU takes into account both inter- and intraprostatic differ-
ences in acoustic and thermal properties, and allows the user to
respond in real-time to the therapy.
Following therapy, patients may leave
the hospital the same day with the SPC
in place. A minimal amount of oral
analgesia is usually required. Trial of
voiding may be carried out using a flip-
flow valve, and patients return in one or
more weeks for removal of the SPC.
The SB-500 has some unique features
that differentiate it from other systems
available. The most important feature, as
discussed previously, is the ability to
monitor the HIFU treatment in real
time and respond to tissue changes by
adjusting the input power according to
the particular characteristics of the gland
being treated. This and other features are
listed in BOX 2. The reflectivity index
measurement (RIM) is an important
safety feature that analyzes the real-time
B-mode image of the rectal wall
immediately in front of the transducer
and digitally compares it to the stored
image taken prior to therapy. The RIM is
a composite score that alerts the user to
any differences between these two images
either caused by patient movement or
gland swelling. If the score is greater
than a certain threshold then the device
will automatically stop and alert
the clinician.
Other important safety features include
real-time rectal wall distance monitoring,
rectal wall temperature monitoring, rever-
beration detection (to alert the user to the
presence of trapped air bubbles), inde-
pendent HIFU monitoring via watchdog
timer circuitry and an emergency stop
button to disable HIFU delivery at any
time during the treatment.
Management System
The SiMS software provides a controlled
interface to the Prostate Therapy soft-
ware, and has been designed with the longer term aim of
patient tracking (as part of a registry) and user training.
There are three main features: login control that ensures that
only those who have been accredited may use the system;
data entry, which creates a database of demographic preoper-
ative features of all patients treated; and a training module
that will allow users to run through treatments in a control-
led manner, either during primary training or as part of
refresher courses.
Figure 6. (A) Multisliced, from base to the apex, treatment planning screen. (B) 3D treatment planning
screen with transverse, saggital and coronal plane imaging.
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Training, waste disposal & equipment required
The current training requirements for clinicians wishing to use
the SB-500 are given in TABLE 1.
The device has very few disposables. On top of a urological
day-case suite with cystoscopy facilities, degassed water (<3 ppm
oxygen) and nonsterile sheaths are all that are required.
Clinical profile & postmarketing findings
Phase I, II & III
The SB-500 has been granted CE marking in Europe and US
FDA-approved clinical trials are currently on-going. The results
of a multicenter Japanese trial were published in 2005 [18] and a
multicenter European trial assessing the SB-500 is currently
underway, which should report back in 2007. Transrectal
HIFU for PCa was reviewed by the National Institute for
Health and Clinical Excellence in 2005 and, following its
report, was cleared for use in the UK within the National
Health Service [101].
A problem facing all new technologies used to treat organ-
confined PCa is the length of time required to generate out-
come data. True figures regarding the disease-specific mortality
following radical prostatectomy have only recently become
available, and these show only a modest improvement in
survival at 10 years after treatment versus watchful waiting [3].
Owing to this, proxy measures of outcome must be used, with
biopsy negativity and American Society for Therapeutic Radi-
ology and Oncology (ASTRO) criteria the most common. A
recent paper has shown that a low PSA nadir following treat-
ment is strongly correlated with good outcome on subsequent
post-treatment biopsy [19], and evidence of persistent enhance-
ment on post-treatment contrast-enhanced magnetic resonance
also strongly predicts both failure on biopsy and subsequent
PSA nadir [20].
The largest case series of patients treated with the SB-500
comes from Uchidas group in Japan. This group have shown
that they were able to achieve a biopsy negative rate of 87%
6 months after treatment in men with presumed localized
PCa [21], with a PSA nadir of less than 1ng/ml in 72% of
patients treated (63 patients). At a mean of 5-years follow-up
they showed a freedom from biochemical recurrence (based on
ASTRO criteria) of 78% [22], in particular, patients with a pre-
treatment PSA of 10 ng/ml or less demonstrated 94 and 77%
biochemical disease free survival at 4- and 5-years follow-up,
respectively (181 patients). It is important to note that this
group were not using visually directed HIFU in their series;
they used predetermined power levels defined from in vitro and
in vivo experimentation [22]. This series compares very favorably
Table 1. Current training requirements for users of the Sonablate®-500.
Observation Minimum of three cases at a recognized center
Off-line training On the device using the Sonablate® Information Management System software
Didactic lectures A series of lectures covering the principles of high-intensity focused ultrasound,
techniques of treatment, follow-up strategies and trouble-shooting
Proctored cases An accredited trainer visits the users’ center and oversees treatment. An experienced
device specialist teaches the theater support staff device set-up, preparation and patient
safety. This may be a variable number of sessions until the user is deemed competent
Supervision by experienced applications specialist To help trouble-shoot and answer questions
Independent practice Following ‘sign off’ by a different accredited trainer
Table 2. Comparison of mean PSA nadirs achieved following trans-rectal HIFU using different devices.
Study Device Treatment
method Patient no. PSA nadir target
(ng/ml) % achieving Mean nadir
ng/ml Ref.
Chaussy and Thüroff Ablatherm Algorithm 184 0.5 61 1.65 [42]
Gelet et al. Ablatherm Algorithm 82 1.0 56 1.02 [41]
Thüroff et al. Ablatherm Algorithm 402 Not given Not given 1.85 [43]
Blana et al. Ablatherm Algorithm 137 0.1
0.5 56
83 Not given [44]
Uchida et al. SB-500 Algorithm 63 0.2
1.0 32
72 1.38 [22]
Illing et al. SB-500 Visually directed 25 0.2 84 0.15 [17]
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with a recent study by Potters and colleagues that compared
seven year outcome data between cohorts undergoing radical
surgery (RP) (746 patients), external beam radiotherapy
(EBRT) to a minimum 70 Gy (340 patients) and low-dose rate
seed brachytherapy (LDR BT) (733 patients) [23] . The onco-
logical outcome was defined as freedom from biochemical
recurrence (FBR) based on ASTRO criteria for EBRT and
LDR-BT, and PSA of less than 0.2 for RP. FBR was similar in
all three groups; 74, 77 and 79% at 7 years for LDR-BT, EBRT
and RP, respectively.
Proponents of visually directed HIFU suggest that lower PSA
nadirs may be achieved using direct visual feedback to tailor
treatment to the individual [17]. Comparison of mean nadirs
achieved between visually directed HIFU and other HIFU
devices (or indeed with the SB-500, when using the pre-set
energies) is given in TAB L E 2 . An example of images taken before
and after visually directed HIFU are given in FIGURE 7.
The adverse event rate for this procedure has been described by
Uchida and colleagues [22]. Having treated 181 patients, they
found a presphincteric stricture rate of 22%, epidiymitis occur-
ring in 6%, a rectourethral fistula in 0.5%, erectile dysfunction in
previously potent men of 20% and no stress incontinence lasting
more than 1month. In the cases of presphincteric strictures all
were managed with periodic urethral dilatation. The experience of
UK clinicians using visually directed HIFU is similar – at a recent
meeting of European users of the SB-500, a cohort of 81 patients
treated in London was described in which the stricture rate was
15%, infection rate 6% and erectile dysfunction in previously
potent men of 25%. In this group, grade 1 stress incontinence
persisted more than 3 months in 4% of those treated [LESLIE TA,
PERS . C OM M. ]. Overall, these figures are very acceptable compared
with other radical therapies such as radical prostatectomy, which
even in the hands of high volume surgeons may have a long-term
incontinence rate (requiring surgical intervention) of almost
7% [24]. It has been the experience of those using the Ablatherm®
device that the postprocedure stricture rate is reduced by the
administration of a preprocedural transurethral resection of the
prostate (TURP). In one study, additional de-obstruction
procedures were required in 27% of those undergoing HIFU
alone and in 8% of those with combined resection [25]. This must
therefore be considered by the physician – should 100% of
patients undergo the risks associated with transurethral resection,
rather than only those who require intervention subsequently?
In an attempt to further reduce the impotence rates, the
‘neurovascular bundle’ detection system has been developed (see
Patient selection & preparation). This relies upon the assump-
tion that neurological mechanism for erection is related anatomi-
cally to the vascular bundles lying antero–lateral to the prostate
capsule. While this is possible, there are no clinical studies yet
available that demonstrate this association. A further caveat
remains that by deliberately undertreating portions of the gland,
the risk of residual disease is greater.
Alternative devices
See TAB L E 3 .
It has been shown that HIFU using the SB-500 has many of
the desirable attributes of a new ablative technology (BOX 1),
incorporated into a highly mobile and expandable treatment
platform. It may be administered under local/regional anesthe-
sia; however, the trend, certainly in Europe, is to use general
anesthesia. Real-time monitoring of the treatment may be per-
formed, but more importantly, the information gained from
the monitoring may be used by the clinician to guide therapy in
a ‘visually directed’ manner. This is the key feature that differ-
entiates it from other transrectal HIFU devices currently availa-
ble. So far the oncological data looks promising – although
long-term results are not available, 5-year data is now emerging
that appears comparable with all of the current mainstream
modalities for the treatment of organ-confined PCa. The side-
effect profile also appears very promising – reported
incontinence, erectile dysfunction and infection rates all appear
better than current modalities. The urethral stricture rate is
high and currently under evaluation [LESLIE TA, PERS. COMM.].
Table 3. Competing minimally invasive devices and technologies in the field of organ confined prostate cancer.
Technique Background Ref.
Ablatherm-HIFU Only other transrectal HIFU device in this field. Uses three preset algorithms for primary, radiation
failure or prior HIFU failure treatments
Low dose rate brachytherapy Permanently implanted radioactive seeds. Widely used in the USA and Europe for primary disease in
combination with external beam radiotherapy
High dose rate brachytherapy Temporary insertion of radioactive sources. Used mainly for high risk disease [45]
Cryotherapy Mainly used for recurrent disease following other forms of therapy. Criticized for adverse event rate [46]
Radiofrequency ablation Investigational for recurrent prostate cancer [47]
Photodynamic therapy Investigational for primary and recurrent prostate cancer [48]
Interstitial rods Stalled in development [49]
HIFU: High-intensity focused ultrasound.
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Further attractions of HIFU are that it is repeatable, of
relatively low running cost and does not provide a therapeu-
tic impasse – surgery and radiotherapy, as well as further
HIFU sessions, are possible following initial treatment
failure [22].
One of the concerns regarding population screening for PCa
in the healthy population is that the available therapies for it
may cause significant harm to the patient. This goes against one
of the five key principles of an effective screening program –
that the benefits of treatment for a condition must outweigh
Figure 7. An example of a Sonablate®-500 treatment follow-up. Axial, T1-weighted gadolinium contrast-enhanced magnetic resonance (MR) images taken
1 min post injection of a patient with T2b prostate cancer. 58-year-old male, pretreatment PSA 7.42, prostate volume 20 ml, Gleason score 3+4, 2/6 cores positive;
left peripheral zone at mid-gland and base. (A) Pretreatment image showing an enhancing region suspicious of cancer in the left peripheral zone; (B) 2weeks
after treatment, lack of contrast uptake within the prostate consistent with coagulation necrosis; (C) 2 months after treatment, shrinkage of the necrotic volume
and typical 'double rim'; and (D) 6 months after treatment, no residual prostate tissue on MR, unrecordable PSA and no evidence of residual disease on transrectal
ultrasound guided biopsy of 7.5 ml tissue seen abutting the sphincter at ultrasound.
PSA: Prostate specific antigen.
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Illing & Emberton
Expert Rev. Med. Devices 3(6), (2006)
the risks [26]. Not taking into account the problematic nature of
the PSA test itself, having a potential therapy that can offer
comparable oncological efficacy with a lower adverse event rate
may encourage more men to come forward for screening, thus
increasing the diagnostic pick-up.
Expert commentary
The trend in all surgical disciplines is for less-invasive treat-
ments. Open surgery has given way to laparoscopic procedures
in many areas, and needle-ablative therapies (such as cryother-
apy and radiofrequency ablation) are gaining ground [27,28].
The next conceptual change is the ability to treat entirely
noninvasively – and in HIFU this is realized.
The key difference between the SB-500 and other current
transrectal HIFU technology is the ability for the user to
tailor treatment to the individual. Other systems may have
real-time imaging, however, if the treatment delivered is
derived from a preset algorithm, any input from the user over
defining the margins of the prostate is obviated. Clinicians
familiar with transrectal ultrasound will acknowledge that
the characteristics of prostate glands differ between patients.
Even men who have had no prior therapy may have glands of
different density and with different patterns of micro- or
macrocalcification. Just as the amount of pressure that is
required to exert on the scalpel is based upon the real-time
characteristics of the tissue it is passing through, so is the
amount of energy required to cause ablation within the pros-
tate gland. It is hoped that the early outcomes based on PSA
nadir [17] can be translated into medium-term biochemical
and histological freedom from disease, and ultimately
survival benefit.
Future developments
There is a great deal of work underway in the field of focused
ultrasound, both clinically and in the laboratory. In 2006, inves-
tigation into aspects of HIFU have generated over 1 million
pounds in UK government research grants from the Engineering
and Physical Sciences Research Council alone [102,103].
Considerable work has already taken place into the develop-
ment of probes for other HIFU applications and phased array
transducer technology [29]. Most clinical devices in use have
either single-element therapeutic transducers or multielement
arrays that act as a single element. Transducers with annular
arrays, allowing the focal point to be electronically moved
towards and away from the transducer face, and 2D arrays
that allow horizontal, lateral and vertical translation of the
focal point without moving the transducer itself, have already
been constructed for experimental purposes (FIGURE 8). Cou-
pled with this, speckle tracking technology is in development,
which may allow software to follow the movement of a target
over time such as through the respiratory cycle, or if the target
organ changes shape during the procedure due to edema [30].
This paves the way for a system that does not have to physi-
cally move during the treatment, but also accounts for any
intraoperative changes automatically.
Visual changes are not the only method of real-time feed-
back. Tissue elastography [31] and ultrasound thermometry [32]
are in development, but remain experimental; magnetic reso-
nance imaging (MRI) [33] may accurately detect temperature
changes, however, MRI devices are costly, do not provide feed-
back as instantaneously as B-mode ultrasound and have not
been used clinically in the setting of transrectal prostate HIFU.
Novel methods enhancing the effect of focused ultrasound
are in development. Injected microbubbles have not only been
used as a contrast agent, but also to enhance ablation [34] and
aid the delivery of genes and chemotherapy [35]. Added to this
are the potential synergistic effects of combining focused ultra-
sound with ionizing radiation, which have yet to be explored,
but which may have a role in the treatment of high-risk or
locally advanced disease.
Lastly, interest in the effect of ablative technologies on immune
upregulation [36], potentially provoke the body into producing an
innate antitumor response following treatment, is growing.
Five-year view
In 5-years’ time the field of PCa therapy may have altered radi-
cally. Not only will new drugs and devices have emerged (possibly
based on those areas outlined above), but there may also have
been a paradigm shift in the way that early disease is viewed.
Whatever the modality, the current treatment for organ-confined
disease is ‘radical’ – the whole gland is treated, as well as the PCa
within it. The reasons for this are straightforward; PCa may be
multifocal in nature, detection of small foci of disease has been
difficult and the tools to perform such precise treatment were
missing. Already this picture has changed – a range of new modal-
ities for targeted treatment have emerged, of which HIFU is argu-
ably the most promising [37], and improvements in imaging and
biopsy technique allow greater levels of confidence that all signifi-
cant foci of disease have been accounted for [38]. There is no doubt
that PCa can be multifocal, but if the targeting and treatment
Figure 8. (A) Annular array electrode laser-scribed on convex side. (B)
Annular array installed in Sonablate®-500 HIFU probe. (C) Cylindrical 2D array
electrode laser-scribed on convex side of piezocomposite material prior to
forming, and (D) completed cylindrical HIFU array transducer assembled
from [29].
HIFU: High-intensity focused ultrasound.
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methods are sufficiently accurate there is the potential for a ‘male
lumpectomy’, much in the same way as radical mastectomy has
been superseded by lumpectomy for early-stage breast cancer in
women [39]. This has the potential to greatly reduce the associated
side effects of radical treatment for PCa, and indeed trials are
currently underway to assess the feasibility of this approach.
Information resources
The International Symposium for Therapeutic Ultrasound
Cancer Research UK
The Prostate Cancer Charity
Focus Surgery
Conflict of interest
Rowland Illing is supported by a grant from Misonix. Mark
Emberton has acted as a paid consultant to Misonix. Misonix
is the European manufacturor and distributor of the
Sonablate device.
Key issues
High-intensity focused ultrasound (HIFU) is a noninvasive therapy that has the potential to treat prostate cancer in a
radical manner.
The Sonablate®-500 is the only transrectal device currently available that uses intraoperative feedback to guide treatment and to
tailor it to the individual.
Early data from this technique look promising with medium-term outcome data from less tailored treatments looking similar to
results from standard therapies.
The published side-effect profile following Sonablate-HIFU is better than current standard therapies.
There is a great deal of interest in this field and developments are underway to refine both the conduct of therapy and the devices
in use.
There is potentially a paradigm shift in the way early-stage prostate cancer is treated – more accurate diagnosis coupled with the
accuracy of HIFU could pave the way to widespread use of focal therapy for early-stage disease.
Papers of special note have been highlighted as:
• of interest
•• of considerable interest
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Illing & Emberton
Expert Rev. Med. Devices 3(6), (2006)
the conduct of therapy. BJU Int. 98(6),
1187–1192 (2006).
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19 National Institute for Health and Clinical
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20 Uchida T, Illing RO, Cathart PJ,
Emberton M. To what extent does PSA
Nadir predict subsequent treatment failure
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BJU Int.98(3), 537–539 (2006).
First paper to define the association
between PSA nadir following prostate
HIFU and outcome.
21 Kirkham APS, Hoh I, Illing RO,
Freeman A, Emberton M, Allen C.
Magnetic resonance imaging of the prostate
after high intensity focused ultrasound.
Presented at the Annual Radiological Society
of North America (RSNA), Chicago, USA,
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22 Uchida T, Ohkusa H, Nagata Y, Hyodo T,
Satoh T, Irie A. Treatment of localized
prostate cancer using high-intensity focused
ultrasound. BJU Int. 97(1), 56–61 (2006).
Provide the largest case series of patients
treated with the Sonablate®-500 (SB-
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Five years experience of transrectal high-
intensity focused ultrasound using the
Sonablate device in the treatment of
localized prostate cancer. Int. J. Urol. 13(3),
228–233 (2006).
Provide the largest case series of patients
treated with the SB-500.
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36 Mitragotri S. Healing sound: the use of
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49 Moore CM, Nathan TR, Lees WR et al.
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356–363 (2006).
50 Tucker RD. Use of interstitial temperature
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17(8), 601–607 (2003).
101 National Institute for Health and Clinical
Excellence.Interventional procedure
guideline 118 – high-intensity focused
ultrasound for prostate cancer – guidence
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102 Engineering and Physical Sciences
Reasearch Council (EPSRC). Funding
103 Engineering and Physical Sciences
Reasearch Council (EPSRC)
Rowland Illing
Honorary Research Fellow, The Clinical
Effectiveness Unit, The Royal College of Surgeons
of England, 35/43 Lincolns Inn Fields, London,
Clinical Fellow, The Institute of Urology &
Nephrology, University College Hospital,
London WC1E 3DB, UK
Tel.: +44 207 869 6600
Fax: +44 0207 869 6644
•Mark Emberton
Deputy Director, The Clinical Effectiveness
Unit, The Royal College of Surgeons of England,
35/43 Lincolns Inn Fields, London, WC2A
Consultant Urological Surgeon, The Institute of
Urology & Nephrology, University College
Hospital, London WC1E 3DB, UK
Tel.: +44 207 869 6600
Fax: +44 207 869 6644
For Electronic Distribution Only, Not to be Distributed in Print Form
... Often compared to Ablatherm is the Sonablate, produced by Sonacare Medical [96]. Similar to the Ablatherm, this system also displays the MRI image contours of the volume onto the real-time ultrasound images. ...
... The other three rely on apnea induced during general anesthesia, which is associated with long procedural times and additional complications [111,112]. Consequently, despite the advanced path-planning capabilities of many of these systems [52,53,96,97], such as the Alpius 900 system, they are not suitable for dynamically moving organs. As a result, these systems are often limited to organs such as the prostate, thyroid, etc. ...
Full-text available
This paper provides an overview of current robot-assisted high-intensity focused ultrasound (HIFU) systems for image-guided therapies. HIFU is a minimally invasive technique that relies on the thermo-mechanical effects of focused ultrasound waves to perform clinical treatments, such as tumor ablation, mild hyperthermia adjuvant to radiation or chemotherapy, vein occlusion, and many others. HIFU is typically performed under ultrasound (USgHIFU) or magnetic resonance imaging guidance (MRgHIFU), which provide intra-operative monitoring of treatment outcomes. Robot-assisted HIFU probe manipulation provides precise HIFU focal control to avoid damage to surrounding sensitive anatomy, such as blood vessels, nerve bundles, or adjacent organs. These clinical and technical benefits have promoted the rapid adoption of robot-assisted HIFU in the past several decades. This paper aims to present the recent developments of robot-assisted HIFU by summarizing the key features and clinical applications of each system. The paper concludes with a comparison and discussion of future perspectives on robot-assisted HIFU.
... The main difference is that the ultrasound waves are concentrated at a focal point, transferring energy to the tissue, which causes a rapid increase in temperature to above 70 °C. The size of the focal lesion can be varied, but is typically cylindrical in shape with a diameter and length of approximately 3 and 11 mm respectively (Illing and Emberton, 2006). The focal lesion is then rastered through the tumour to ensure complete coverage. ...
Minimally invasive therapies aim to deliver effective treatment whilst reducing off-target burden, limiting side effects, and shortening patient recovery times. Remote navigation of untethered devices is one method that can be used to deliver targeted treatment to deep and otherwise inaccessible locations within the body. Minimally invasive image-guided ablation (MINIMA) is a novel thermal ablation therapy for the treatment of solid tumours, whereby an untethered ferromagnetic thermoseed is navigated through tissue to a target site within the body, using the magnetic field gradients generated by a magnetic resonance imaging (MRI) system. Once at the tumour, the thermoseed is heated remotely using an alternating magnetic field, to induce cell death in the surrounding cancer tissue. The thermoseed is then navigated through the tumour, heating at pre-defined locations until the entire volume has been ablated. The aim of this PhD project is to develop MINIMA through a series of proof-of-concept studies and to assess the efficacy of the three key project components: imaging, navigation, and heating. First, an MR imaging sequence was implemented to track the thermoseeds during navigation and subsequently assessed for precision and accuracy. Secondly, movement of the thermoseeds through a viscous fluid was characterised, by measuring the effect of different navigation parameters. This was followed by navigation experiments performed in ex vivo tissue. To assess thermoseed heating, a series of in vitro experiments were conducted in air, water, and ex vivo liver tissue, before moving onto in vivo experiments in the rat brain and a murine subcutaneous tumour model. These final experiments allowed the extent of cell death induced by thermoseed heating to be determined, in both healthy and diseased tissue respectively.
... The Sonablate does not have a real-time imaging system while the treatment is given, but instead alternates between the treatment mode and image acquisition to create an image overlay that is used to detect patient movement; this is achieved by placing images of treatment planning along with images taken during treatment, if both images are aligned, it is indicative that there has been no movement of the patient (Figure 6) [16]. ...
Full-text available
The minimally invasive, image-guided therapies are a clear option in the urologists' armamentarium to treat BPH and prostate cancer. During the last decade, advances in the HIFU systems improved the capacities to scan, fuse MR images to target a specific zone, situation that improved the safety and possibility to ablate the cancer in a focal-ized location or a whole gland ablation, preserving continence and erections, with a proper selection of patients, with good results, comparable with surgery or radiation. In some post radiation failures, it is a very safe option to treat the recurrent cancer. In the case of BPH, the flexibility to ablate exclusively the prostate enlargement, preserving the urethra is a great advantage, considering a fast procedure, no bleeding, and a highly precise treatment, with improvement in the voiding function, improving IPSS and uroflowmetry parameters.
... The Sonablate does not have a real-time imaging system while the treatment is given, but instead alternates between the treatment mode and image acquisition to create an image overlay that is used to detect patient movement; this is achieved by placing images of treatment planning along with images taken during treatment, if both images are aligned, it is indicative that there has been no movement of the patient (Figure 6) [16]. ...
Full-text available
The minimally invasive, image-guided therapies are a clear option in the urologists' armamentarium to treat BPH and prostate cancer. During the last decade, advances in the HIFU systems improved the capacities to scan, fuse MR images to target a specific zone, situation that improved the safety and possibility to ablate the cancer in a focal-ized location or a whole gland ablation, preserving continence and erections, with a proper selection of patients, with good results, comparable with surgery or radiation. In some post radiation failures, it is a very safe option to treat the recurrent cancer. In the case of BPH, the flexibility to ablate exclusively the prostate enlargement, preserving the urethra is a great advantage, considering a fast procedure, no bleeding, and a highly precise treatment, with improvement in the voiding function, improving IPSS and uroflowmetry parameters.
... Transcranial HIFU systems 137,338 typically have an initial focal spot of around 2 mm 2 that reaches around 44 o C, but then increases considerably as the temperature increases after consecutive applications. Rectal HIFU probes can ablate regions of around 3x3x10-12 mm, and can reach temperatures >80 o C near instantaneously but are reduced to focal depths of 40-50 mm 339 . At present we have demonstrated variable ablation volumes with a radius between 8.5-45 mm 2 , which can be further reduced by applying the AMF for less than 1 minute. ...
Conference Paper
Delivering a therapy with precision, while reducing off target effects is key to the success of any novel therapeutic intervention. This is of most relevance in the brain, where the preservation of surrounding healthy tissue is crucial in reducing the risk of cognitive impairment and improving patient prognosis. Our scientific understanding of the brain would also benefit from minimally invasive investigations of specific cell types so that they may be observed in their most natural physiological environment. Magnetic particles based techniques have the potential to deliver cellular precision in a minimally invasive manner. When inside the body, Magnetic particles can be actuated remotely using externally applied magnetic fields while their position can be detected non-invasively using MRI. The magnetic forces applied to the particles however, rapidly decline with increasing distance from the magnetic source. It is therefore critical to understand the amount of force needed for a particular application. The properties of the magnetic particle such as the size, shape and magnetic content, as well as the properties of the applied magnetic field, can then be tailored to that application. The aim of this thesis was to develop magnetic particle based techniques for precise manipulation of cells in the brain. Two different approaches were explored, utilising the versatile nature of magnetic actuation for two different applications. The first approach uses magnetic nanoparticles to mechanically stimulate a specific cell type. Magnetic particles conjugated with the antibody ACSA-1 would selectively bind to astrocytes to evoke the controlled release of ATP and induce a calcium flux which are used for communication with neighbouring cells. This approach allows for the investigation into the role of astrocytes in localised brain regions using a naturally occurring actuation process (mechanical force) without effecting their natural environment. The second approach uses a millimetre sized magnetic particle which can be navigated through the brain and ablate localised regions of cells using a magnetic resonance imaging system. The magnetic particle causes a distinct contrast in MRI images, allowing for precise detection of its location so that it may be iteratively guided along a pre-determined path to avoid eloquent brain regions. Once at the desired location, an alternating magnetic field can be applied causing the magnetic particle to heat and deliver controllable, well defined regions of cell death. The forces needed for cell stimulation are orders of magnitude less than the forces needed to guide particles through the brain. Chapters 4 and 5 use external magnets to deliver forces in the piconewton range. While stimulation was demonstrated in small animals, scaling up this technique to human proportions remains a challenge. Chapters 6 and 7 use a preclinical MRI system to generate forces in the millinewton range, allowing the particle to be moved several centimetres through the brain within a typical surgical timescale. When inside the scanner, an alternating magnetic field causes the particle to heat rapidly, enabling the potential for multiple ablations within a single surgery. For clinical translation of this technique, MRI scanners would require a dedicated propulsion gradient set and heating coil.
... The formation of the HIFU lesion in the prostate is on the order of a few seconds, for instance 3 seconds of exposure and 6 seconds of pause in the case of the Sonablate ® system (Illing and Emberton, 2006), which is a short time to allow the monitoring of the creation of every single lesion by any potential monitoring technique. However, the build-up of the global ablated area can be monitored by localising and characterising individual HIFU lesions after their formation one after another. ...
Conference Paper
Prostate cancer remains a major healthcare issue. Limitations in current diagnosis and treatment monitoring techniques imply that there is still a need for improvements. The efficacy of prostate cancer diagnosis is still low. High intensity focused ultrasound ablation is an emerging treatment modality, which enables the noninvasive ablation of pathogenic tissue. Successful focal ablation treatment of prostate cancer is critically dependent on accurate diagnostic means and would be greatly benefited by a monitoring system. While magnetic resonance imaging remains the gold standard for prostate imaging, its wider implementation remains prohibitively expensive. Conventional ultrasound is currently limited to guiding biopsy. Elastography techniques are emerging as a promising imaging method, as cancer nodules are usually stiffer than adjacent healthy tissue, and even stiffer in the case of thermally ablated tissue. In this thesis, a novel transurethral elastography approach is proposed for the diagnosis of prostate cancer and its focal ablation monitoring, based on the transmission and detection of shear waves through the urethral wall. A viscoelastic wave propagation model is developed, using a finite difference time domain technique and based on a Kelvin-Voigt fractional derivative constitutive law. Validation of the model is achieved by high-speed camera tests carried out on translucent tissue-mimicking media. A Reverse Time Migration and a Genetic Algorithm techniques are proposed for reconstructing the parameters of the stiff lesion. A comparative study of the two techniques is presented. The Reverse Time Migration method finds the stiff lesion area in short computational time. The Genetic Algorithm provides full reconstruction of the location, size and stiffness of the lesion, however the computation time is much longer. A combination of both techniques achieves improved results by combining the speed of the Reverse Time Migration and the full reconstruction capacity of the Genetic Algorithm. Preliminary results support the feasibility of the method and encourage further investigation.
Full-text available
Medical therapies achieve their control at expense to the patient in the form of a range of toxicities, which incur costs and diminish quality of life. Magnetic resonance navigation is an emergent technique that enables image‐guided remote‐control of magnetically labeled therapies and devices in the body, using a magnetic resonance imaging (MRI) system. Minimally INvasive IMage‐guided Ablation (MINIMA), a novel, minimally invasive, MRI‐guided ablation technique, which has the potential to avoid traditional toxicities, is presented. It comprises a thermoseed navigated to a target site using magnetic propulsion gradients generated by an MRI scanner, before inducing localized cell death using an MR‐compatible thermoablative device. The authors demonstrate precise thermoseed imaging and navigation through brain tissue using an MRI system (0.3 mm), and they perform thermoablation in vitro and in vivo within subcutaneous tumors, with the focal ablation volume finely controlled by heating duration. MINIMA is a novel theranostic platform, combining imaging, navigation, and heating to deliver diagnosis and therapy in a single device.
A 34-mm aperture transducer was designed and tested for proof of concept to ablate tissues using an endocavity histotripsy device. Several materials and two drivers were modeled and tested to determine an effective piezoelectric–matching layer combination and driver design. The resulting transducer was fabricated using 1.5 MHz porous PZT and PerFORM 3-D printed acoustic lenses and was driven with a multicycle class-D amplifier. The lower frequency, compared to previously developed small form factor histotripsy transducers, was selected to allow for more efficient volume ablation of tissue. The transducer was characterized and tested by measuring pressure field maps in the axial and lateral planes and pressure output as a function of driving voltage. The axial and lateral full-width-half-maximums of the focus were found to be 6.1 and 1.1 mm, respectively. The transducer was estimated to generate 34.5-MPa peak negative focal pressure with a peak-to-peak driving voltage of 1345 V. Performance testing was done by ablating volumes of bovine liver tissues ( ${n} = {3}$ ). The transducer was found to be capable of ablating tissues at its full working distance of 17 mm.
Astrophysical objects, such as stars in their early evolutionary stages (so called Young Stellar Objects), neutron stars, black holes and active galactic nuclei often present highly collimated outflows of particles, called jets. All of these systems are characterised by accretion of surrounding matter onto their gravity centre. Accretion takes place through a disk, formed by dust and plasma (ionised gas) orbiting the central object. The jets are launched from inner parts of the disk, and propagate to distances much larger than the sizes of the systems launching them. In this way, the accretion-ejection processes can have an important impact on the environment to large distances, and on the formation and evolution of astrophysical objects. Understanding of accretion-ejection phenomena has grown enormously in the past decade, and physical processes underlying the phenomenological description of the problem are being elucidated. The role of magnetic fields has become evident (e.g. Murphy et al. 2010; Sheikhnezami et al. 2012).
Introduction The treatment of localized prostate cancer seeks to minimize the impact on sexual function and urinary continence. In this respect, therapy with high-intensity focused ultrasound offers important results. We present our experience with this technique in 2 Spanish centers. Material and methods We conducted a retrospective review of 75 patients with localized prostate cancer treated with high-intensity focused ultrasound between March 2007 and July 2016. The oncological results and perioperative complications were assessed, as well as the impact on sexual function and continence. Results A total of 67 patients were analyzed. The mean follow-up was 7.2 years. The PSA nadir was 0.2 ng/ml (0–3), 24 patients (35.5%) presented biochemical recurrence, and 18 underwent a further biopsy, with 10 cases (55.5%) presenting disease recurrence. The overall biochemical relapse-free survival at 5 and 8 years was 93.2 and 80.5%, respectively. The cancer-specific survival at 5 and 8 years was 96% in both cases. In the postoperative period, 50 patients (74.6%) were continent, 16 (23.9%) reported mild incontinence, and one (1.5%) reported moderate incontinence. The median International Index of Erectile Function-5 before and after the surgery was 17 (5–25) and 16 (2–23) points, respectively. Nine patients reported de novo erectile dysfunction (13.5%). Conclusion High-intensity focused ultrasound appears to be a safe alternative for the treatment of localized prostate cancer, especially for low-risk localized prostate cancer. In our experience, this technique offers advantages in preserving urinary continence, and the medium-term oncological results are encouraging. Given the natural progression of prostate cancer, long-term studies with a larger number of cases are needed to corroborate these results.
Conference Paper
We evaluated 181 patients with localized prostate cancer treated with high‐intensity focused ultrasound (HIFU) for biochemical disease‐free rate, safety, morbidity and predictors of biochemical outcome. A total of 181 patients underwent HIFU with the Sonablate‐500 and with at least 12 months of follow‐up. Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The biochemical disease‐free rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease‐free rates at 3 years for patients with pretreatment PSA less than 10 ng/ml, 10.01 to 20.0 ng/ml and more than 20.0 ng/ml were 94%, 75% and 35%, respectively (p<0.0001). According to multivariate analysis preoperative PSA (p<0.0001) was a significant independent predictor of time to biochemical recurrence. HIFU therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/ml.
Purpose: HIFU is an alternative minimal invasive treatment option for patients with localised prostate cancer. A transurethral resection before HIFU does reduce the volume of the gland, especially the area of the so called transitional zone; thus HIFU treatment can be focussed on the remaining peripheral prostate tissue. Furthermore we intend a reduction of the postoperative period of edema-related infravesical obstruction. Patients and Method: We treated 70 patients with bioptic proven, local prostate cancer (T1/T2, N0, M0) in a combination of TUR-P and HIFU (Ablatherm device, EDAP, Lyon, France). The inclusion criteria for the procedure were a PSA level ≤ 15 ng/ml and a Gleason Score ≤ 7. The mean patients age was 66,78 (± 6,3) years, the mean PSA level 7,25 ± (3,5) ng/ml and the mean Gleason Score 5,1 (± 1,2). The mean prostate volume before treatment was 32 (± 11,6) cm3; it was reduced to 22,8 (± 7,2) cm 3 by TUR-P. The follow-up was 15 (± 6,8) months and included in every patient control of PSA and randomised biopsies of the residual prostate gland. The data of all 70 patients were included. Results: The PSA-Nadir was 0,14 (± 0,34) ng/ml and achieved after 3 months. The average PSA level of the last follow up was 0,21 (± 0,38) ng/ml. 94% of the biopsies did not show any vital prostate cancer tissue. The average time of the postoperative (suprapubic) catheter was 7 days (± 4,2). 13,6% of the patients developed an urodynamic relevant bladder outlet obstruction making a second endoscopic intervention necessary. The IPS-Score und Quality of Life didn't change significantly by the treatment. Discussion: Performing a TUR-P before HIFU treatment, the volume of the prostate gland is not an exclusion criteria for HIFU any more. The postoperative edema related obstruction can be shortened to one week in relation to a single HIFU session. Although bladder outlet sclerosis after combined TUR-P and HIFU seems to be high, the incidence could be reduced to nearly 50% compared to the initial patient regime with single HIFU.
To describe the preliminary clinical outcomes of active surveillance (AS), a new strategy aiming to individualize the management of early prostate cancer by selecting only those men with significant cancers for curative therapy, and illustrate the contrast with a policy of watchful waiting (WW).Patients and Methods Eighty men with early prostate cancer began AS at the authors’ institution between 1993 and 2002. Eligibility included histologically confirmed prostatic adenocarcinoma, fitness for radical treatment, clinical stage T1/T2, N0/X, M0/X, a prostate specific antigen (PSA) level of ≤20 ng/mL, and a Gleason score of ≤7. PSA was measured and a digital rectal examination conducted at 3–6 month intervals. The decision between continued monitoring or radical treatment was informed by the rate of rise of PSA, and was made according to the judgment of each patient and clinician. During the same period, 32 men with localized prostate cancer (any T stage, N0/X, M0/X, any PSA, Gleason score ≤7) were managed by WW; hormonal treatment was indicated for symptomatic prostate cancer progression. The PSA doubling time (DT) was calculated using linear regression of ln(PSA) against time, using all pretreatment PSA values.ResultsAt a median follow-up of 42 months, 64 (80%) of the 80 patients on AS remained under observation, 11 (14%) received radical treatment and five (6%) died from other causes. No patient developed evidence of metastatic disease, none started palliative hormone therapy, and there were no deaths from prostate cancer. Of the 11 patients who received radical treatment all remained biochemically controlled with no clinical evidence of recurrent disease. The median PSA DT while on AS was 12 years. Twenty (62%) of the 32 patients on WW remained on observation, eight (25%) received palliative hormonal therapy and four (12%) died, including one from prostate cancer.ConclusionsAS is feasible in selected men with early prostate cancer. The natural history of this disease often appears extremely indolent, and most men on AS will avoid radical treatment. There is a marked contrast between AS (with radical treatment for biochemical progression) and WW (with palliative treatment for symptomatic progression). Ongoing studies are seeking to optimize the AS protocol, and to compare the long-term outcomes with those of immediate radical treatment.
Men with prostate cancer are likely to develop impotence after prostate cancer therapy if the treatment damages the neuro‐vascular bundles (NVB). The NVB are generally located at the periphery of the prostate gland. To preserve the NVB, a Doppler system is used to detect and localize the associated blood vessels. This information is used during the therapy planning procedure to avoid treatment surrounding the blood vessel areas. The Sonablate®500 (Focus Surgery, Inc.) image‐guided HIFU device is enhanced with a pulse‐wave multi‐gate Doppler system that uses the current imaging transducer and mechanical scanner to acquire Doppler data. Doppler detection is executed after the regular B‐mode images are acquired from the base to the apex of the prostate using parallel sector scans. The results are stored and rendered in 3‐D display, registered with additional models generated for the capsule, urethra, and rectal wall, and the B‐mode data and treatment plan itself. The display of the blood flow can be in 2‐D color overlaid on the B‐mode image or in 3‐D color structure. Based on this 3‐D model, the HIFU treatment planning can be executed in automated or manual mode by the physician to remove originally defined treatment zones that overlap with the NVB (for preservation of NVB). The results of the NVB detection in animal experiments, and the 3‐D modeling and data registration of the prostate will be presented.