Jpn J Clin Oncol 2008;38(3)192–199

doi:10.1093/jjco/hym173

Focal Therapy with High-intensity-focused Ultrasound

in the Treatment of Localized Prostate Cancer
Satoru Muto, Takashi Yoshii, Keisuke Saito, Yutaka Kamiyama, Hisamitsu Ide and Shigeo Horie

Department of Urology, Teikyo University School of Medicine, Tokyo, Japan

Received July 21, 2007; accepted December 2, 2007; published online February 15, 2008

Background: We evaluated the efficacy and feasibility of high-intensity-focused ultrasound

(HIFU) for localized prostate cancer.
Methods: Seventy patients received HIFU using Sonablatew 500 (Focus Surgery, IN, USA).
In patients whose cancer was confined to only one lobe by multi-regional biopsies, total peri-
pheral zone and a half portion of transitional zone were ablated (focal therapy). Otherwise,
patients received whole organ ablation (whole therapy). Scheduled biopsies were performed

Downloaded from jjco.oxfordjournals.org by guest on September 20, 2010

at 6 and 12 months after treatment. Pre- and post-HIFU serum testosterone levels were
measured.
Result: The 2-year biochemical disease-free survival (DFS) rates in patients at low, inter-
mediate and high risk were 85.9, 50.9 and 0%, respectively, (P ¼ 0.0028). After 12 months,
81.6% (40/49) of patients were biopsy negative; 84.4% in patients who received whole
therapy, whereas 76.5% in those with focal therapy. The 2-year biochemical DFS rates for
the patients at low and intermediate risk was 90.9 and 49.9%, respectively, in patients with
whole therapy, whereas 83.3 and 53.6% in patients with focal therapy. In patients without
neoadjuvant androgen deprivation, serum testosterone levels continuously decreased after
whole therapy, whereas no changes were seen in those with focal therapy. The patients
whose follow-up biopsies were positive tended to have significantly higher changes in pros-
tate-specific antigen levels than biopsy-negative patients.
Conclusions: In patients with low-risk prostate cancer, HIFU monotherapy resulted in com-
parable immediate cancer control with other modalities. Particularly, focal therapy might offer
a feasible minimally invasive therapeutic option, which maintained serum testosterone level.
To our knowledge, this is the first report that whole, but not focal, therapy affects the serum
testosterone level.

Key words: high-intensity-focused ultrasound – focal therapy – localized prostate cancer –

testosterone

INTRODUCTION Organ-sparing treatments are becoming increasingly popular

among the patients with low-stage disease (3). In addition to
The incidence of prostate cancer had traditionally been lower
cancer control, there are concerns about the frequency and
in Japan than in Western countries, although the mortality
the extent of side effects, such as urinary incontinence and
rate of prostate cancer is rapidly increasing in Japan (1).
erectile dysfunction, which affect the quality of life (QOL)
Increased public awareness and serum prostate-specific
patients. Currently, such concerns tend to have a significant
antigen (PSA) screening have resulted in a change in the
impact on the choice of treatment for localized prostate
stage of prostate cancer noted at the time of diagnosis (2).
cancer (4). High-intensity-focused ultrasound (HIFU) is a
new modality that can be used for local tumor ablation
For reprints and all correspondence: Shigeo Horie, Department of Urology, therapy. During HIFU treatment, focused ultrasound waves
Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo are emitted from a transducer and are absorbed in the target
173-8605, Japan. E-mail: shorie@med.teikyo-u.ac.jp

# 2008 The Author(s).

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://
creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium,
provided the original work is properly cited.

area, thereby inducing coagulation necrosis without causing
damage to the tissue in the path of the ultrasound beam
(5,6). The first clinical application of HIFU was done by
Gelet et al. (7) in the treatment of organ-confined prostate
cancer. Currently, two HIFU devices are available:
Ablatherm HIFU device (EDAP SA, Lyon, France) and
Sonablatew 500 (Focus surgery, IN, USA). The efficacy and
safety of Ablatherm HIFU device for the treatment of loca-
lized prostate cancer has been established (7 – 14). The
Sonablatew 500 was introduced in Japan in 1999. The advan-
tage of this device is that one can monitor the prostate in
situ with ultrasonography during treatment (15,16). Uchida
et al. (15) reported an overall biochemical disease-free rate
of 75% in 47 patients following Sonablatew 500 treatment.
Prostate cancer has been recognized to be a multifocal
disease (17). However, the current evidence suggests that the
clinical significance of the tumor depends on the index or
the size of the largest cancer lesion (18). This evidence
prompted us to use HIFU for the focal therapy of a limited
area of the prostate in low-risk patients. We herein report the
efficacy and the safety of treatment with HIFU using the
Sonablatew device, particularly with respect to its use for
focal therapy.
MATERIALS AND METHODS
PATIENTS
Seventy patients presenting with localized prostate cancer
from July 2003 to August 2006 were included in this study.
The selection criteria for this study were as follows: those
who was .60 years old,TNM stage T1c-T2N0M0, and
biopsy and magnetic resonance imaging (MRI) of the pros-
tate indicating localized disease. All patients were either
unsuitable for radical prostatectomy because of comorbid-
ities or preferred to the treatment with HIFU over surgery or
radiation therapy. All patients provided written informed
consent before entering the study. Patients who were on
anticoagulant therapy, such as warfarin or aspirin, were kept
on their anticoagulant regimens before the procedure. The
study protocol was approved by the ethics committee in our
hospital. Informed consent was obtained from all patients.
HIFU TREATMENT
All 70 patients received HIFU treatment using the
Sonablatew device under general anesthesia. Patients were
placed in the supine position with their legs apart so that
they could be given transrectal HIFU. The treatment was
performed using a transrectal probe that includes a 4 MHz
piezoelectric treatment transducer and a 4 MHz ultrasound
imaging probe. Contiguous HIFU shots were delivered
1.8 mm apart with a 4-s shot duration and a 12-s interval
between shots. The volume to be treated was determined by
an urologist, who used a longitudinal and transverse ultra-
sound imaging system. The area of ablation with HIFU was
Jpn J Clin Oncol 2008;38(3) 193
determined based on the results of digital rectal examination,
multi-regional transrectal ultrasound-guided biopsy more
than 12 cores and preoperative pelvic MRI. We ablated the
peripheral zone of both lobes and the ipsilateral transitional
zone upon the patients’ consent when it was likely that the
signature cancers were localized in one lobe (focal therapy).
Otherwise, the whole organ was ablated with HIFU (Fig. 1).
The patients were discharged on the next day after the
HIFU.
FOLLOW-UP
Scheduled biopsies were done 6 and 12 months after treat-
ment. During the follow-up period, PSA was measured at 3,
6, 12, 18, 24 and 36 months. Serum PSA was analyzed with
chemiluminescent enzyme-linked immunoassay (normal
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range, 4.000 ng/ml). The American Society for Therapeutic
Radiology and Oncology (ASTRO) consensus definition for
biochemical failure, i.e. three consecutive increases in PSA
level after a nadir, was used to define biochemical failure
(19). Time to biochemical failure was defined as a midway
between the PSA nadir and the first of the three consecutive
PSA increases. Distributions of biochemical disease-free sur-
vival (DFS) times were calculated according to the
Kaplan Meier curves and the log-rank test used to determine
the differences between the curves. The risk classification is
based on D’Amico et al. (20). Low risk is defined as clinical
T stage T1c, T2a, Gleason score 6 and PSA ,10 ng/ml.
Conversely, patients with clinical stage T2c disease, a PSA
.20 ng/ml or a biopsy Gleason score of 8 have been
identified to be at high-risk group. For the remaining patients
with PSA levels higher than 10 and 20 ng/ml or lower, a
biopsy Gleason score of 7 or clinical stage T2b has been
identified to be at intermediate risk. Serum testosterone
levels (normal range: 225 – 1039 ng/dl) were measured by
the chemiluminescent immunoassay at 6 months and 1 year.
In all patients, a follow-up sextant biopsy, uroflowmetery
and the disease-targeted questionnaire using University of
California-Los Angeles Prostate Cancer Index (UCLA-PCI)
and International Prostate Symptom Score questionnaires
(IPSS) were performed at 6 months and 1 year.
STATISTICAL CONSIDERATIONS
Student’s t and Fisher’s exact tests were used to compare the
quantitative and categorical variables, respectively. All
P-values ,0.05 reflected statistically significant differences.
RESULTS
PATIENT CHARACTERISTICS
Table 1 summarizes the baseline clinical characteristics of
the patients. Median age was 72 (range, 61 – 80) years. Mean
prostate volume was 33.0 (range, 9.0 – 62.8) cc and the
median pre-HIFU PSA was 4.6 ng/ml (range, 0.0 – 29.5). The
194 Treatment of localized CaP with HIFU
Figure 1. The shaded portion indicates the ablative area. Open circle: urethral preservation. (a) Whole therapy: the whole organ was ablated with high-
intensity-focused ultrasound (HIFU) without urethra. (b) Focal therapy: when multi-regional biopsies more than 12 cores revealed the localization of cancers
in one lobe, the ipsilateral transitional zone and the peripheral zone of both lobes were ablated without urethra.
mean number of positive cores at diagnosis based on a pros-
tate biopsy was 1.6, and the median Gleason score was 6
(range from 4 to 10). Twenty-four cases (34.3%) received
androgen deprivation therapy prior to the procedure, which
was discontinued after HIFU treatment. Twenty-nine cases
(41.4%) received focal therapy, whereas 41 cases (58.6%)
had whole organ treatment. There was no significant differ-
ence in age, initial PSA, PSA density and prostate volume
between the focal and whole therapy groups (Tables 1
and 2). T-stages were distributed as follows: T1c, 32
(78.0%); T2a, 4 (9.8%); T2b, 5 (12.2%) in whole therapy
group and T1c, 25 (86.2%); T2a, 4 (13.8%) in focal therapy
(Table 1).
Among the whole therapy group, 29 of 41 patients
(70.7%) had bilateral positive cores. No patients in focal
therapy group had bilateral positive cores at diagnosis based
on a prostate biopsy (Table 1). The mean HIFU treatment
time was 93.6 min (whole therapy, 109.7 + 38.5 min; focal
therapy, 71.8 + 28.3 min, P ¼ 0.0000).
ONCOLOGICAL RESULTS
At a median follow-up of 34 (range, 8 – 45) months, the effi-
cacy of HIFU treatment was examined in all patients. By the
time of this study was undertaken, no patients had died. The
biopsy-negative rates at 6 months and 1 year were 59 of 67
(88.1%) and 40 of 49 (81.6%), respectively (Table 3). No
difference was seen in the biopsy-negative rates between the
focal and whole therapy groups (6 months: P ¼ 0.8489, 12
months: P ¼ 0.7698) (Table 3). No difference was seen in
the biopsy-negative rates between the androgen deprivation
therapy prior to the HIFU group and no neoadjuvant
hormone therapy groups (6 months: 90.9% versus 86.7%,
P ¼ 0.7076; 12 months: 89.5% versus 76.7%, P ¼ 0.4536).
Patients who had positive biopsies at follow-up preferred to
receive androgen deprivation therapy even though other
treatment options were proposed. PSA levels significantly
decreased after HIFU (at 3 months, 1.78 + 2.55 ng/ml:
P ¼ 0.0000; at 6 months, 2.26 + 2.87 ng/ml: P ¼ 0.0004; at
9 months, 2.55 + 2.55 ng/ml: P ¼ 0.0051; at 12 months,
2.74 + 2.69 ng/ml, P ¼ 0.0066; at 24 months, 3.05 +
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3.13 ng/ml, P ¼ 0.0935; at 36 months, 1.89 + 1.51 ng/ml,
P ¼ 0.0357) (Table 4). The 2-year biochemical DFS rates in
patients at low, intermediate and high-risk were 85.9, 50.9
and 0%, respectively (Fig. 2a). No significant differences
were noted in the 2-year biochemical DFS rates for the
patients at low and intermediate risk treated with between
whole (90.9 and 49.9, respectively) and focal therapy (83.3
and 53.6, respectively) (P ¼ 0.8864 and 0.8843, respect-
ively) (Fig. 2b and c).
DPSA AND THE TREATMENT EFFICACY
To evaluate the amount of focused ultrasound energy
absorbed by the prostate, we examined the change in the
PSA level after the procedure. The PSA increased on the day
after the procedure, presumably due to the destruction of
prostate tissue by HIFU. The increase in the PSA level from
the preoperative values 1 day after the operation (DPSA) was
correlated with the total ablative energy of HIFU that was
used (R ¼ 0.5420, P , 0.0001). DPSA was significantly
higher in patients with negative biopsies at 6 months and
1 year after HIFU monotherapy [DPSA (ng/ml): at 6 months,
128.5 + 114.0 versus 53.3 + 39.4 (biopsy negative versus
biopsy positive), P ¼ 0.019; at 12 months, 124.3 + 102.6
versus 32.8 + 29.0 (biopsy negative versus biopsy positive),
P ¼ 0.043]. Therefore, DPSA might be an alternative
method for predicting the outcome of cancer control.
QOL AND SIDE EFFECTS
The QOL questions (IPSS, Urinary function and bother of
UCLA-PCI) did not differ between the focal therapy and the
whole therapy groups (Table 5). Actually, in the results of
uroflowmetry, maximum and average flow rates did not
differ between these groups (Table 5). The period of indwel-
ling urethral catheter after HIFU was significantly decreased
in focal therapy group when compared with the patients in
the whole therapy group (15.2 + 4.4 versus 19.7 + 7.6 days,
P ¼ 0.0213). The frequency of urethral stricture and
 Jpn J Clin Oncol 2008;38(3) 195

Table 1. Patient characteristics Table 2. Total prostate volume and transitional zone volume before and
after HIFU therapy
Total Whole therapy Focal therapy P
Whole Focal P value
Number of 70 41 (58.6) 29 (41.4)
patients (%) Total prostate
volume (ml)
Age (years)
Pre-HIFU 31.0 + 14.0 35.8 + 11.4 0.1902
Median 72 73 72 0.45
6 months 17.2 + 6.7 26.9 + 13.1 0.0008
Range 61–80 61–79 62– 80
12 months 15.5 + 6.7 30.3 + 16.2 0.0001
Follow-up periods
(M) Transitional zone
volume (ml)
Median 34 37 32 0.66
Pre-HIFU 14.2 + 8.0 14.8 + 6.3 0.7548
Range 8 –45 8– 44 9 –45
6 months 7.0 + 3.1 13.1 + 8.8 0.0008
PSA at diagnosis
(ng/ml) 12 months 7.2 + 3.7 14.7 + 7.8 0.0001
Median 6.8 7.0 5.4 0.29

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Range 1.8–29.5 3.3–29.5 1.8– 25.1
Pre-HIFU PSA
(ng/ml)
Table 3. The results of prostate biopsy after HIFU: PB  6 months: the
Median 4.6 4.6 5.4 0.77 results of prostate biopsy after 6 months after HIFU, PB  12 months: the
Range 0.0–29.5 0.0–29.5 0.2– 25.1 results of prostate biopsy after 12 months after HIFU

Pre-operative
Gleason score (%) Total Whole Focal P value

5 or less 5 (7.1) 3 (7.3) 2 (6.9) PB  6 months

6 32 (45.8) 18 (43.9) 14 (48.3) n 67 39 28
7 21 (30.0) 15 (36.6) 6 (20.7) Negative(%) 59 (88.1) 34 (87.2) 25 (89.3) 0.8489
8– 10 8 (11.4) 3 (7.3) 5 (17.2) Positive(%) 8 (11.9) 5 (12.8) 3 (10.7)
Unknown 4 (5.7) 2 (4.9) 2 (6.9) PB  12 months
Pre-operative n 49 32 17
T-stage (%) Negative(%) 40 (81.6) 27 (84.4) 13 (76.5) 0.7698
T1c 57 (81.4) 32 (78.0) 25 (86.2) Positive(%) 9 (18.4) 5 (15.6) 4 (23.5)
T2a 8 (11.4) 4 (9.8) 4 (13.8)
T2b 5 (7.1) 5 (12.2) 0 (0.0) PB, prostate biopsy.
Location of
positive biopsy
(%)
continent before surgery, 49 were also continent after HIFU.
These results indicate that HIFU treatment did not affect
Unilateral 41 (29.3) 12 (29.3) 29 (100.0)
QOL status of the patients.
Bilateral 29 (70.7) 29 (70.7) 0 (0.0)
Number of 24 (34.3) 17 (41.5) 7 (24.1) 0.32
patients with
hormone therapy
at the time of the CHANGES IN THE SERUM TESTOSTERONE LEVELS AFTER THE
treatment (%) HIFU MONOTHERAPY

PSA, prostate-specific antigen; HIFU, high-intensity-focused ultrasound.

symptomatic urinary tract infection tended to be higher in
whole therapy group [3/35 (8.6%), 4/35 (11.4%), respect-
ively) when compared with the patients in focal therapy
group (1/25: 4.0%, 1/25: 4.0%, respectively), although stat-
istically non-significant. Transient urinary retention was
noted in four patients (5.7%) who received transurethral
resection of prostate (TURP). Of the 52 patients who were
We examined the serum testosterone levels before and after
HIFU monotherapy. In patients without neoadjuvant
hormone therapy group who received whole therapy, the tes-
tosterone levels decreased at 6 and 12 months after HIFU,
whereas no changes were seen in patients who received focal
therapy without neoadjuvant hormone therapy group. Serum
testosterone levels (ng/ml) were: pre-HIFU, 454.5 + 171.6
versus 378.2 + 141.6 (focal therapy versus whole therapy),
P ¼ 0.148; at 6 months, 465.7 + 154.8 versus 312.6 + 91.7
(focal therapy versus whole therapy), P ¼ 0.0006; at 12
months, 488.1 + 186.1 versus 262.1 + 151.4 (focal therapy
versus whole therapy), P ¼ 0.0002 (Table 5).
196 Treatment of localized CaP with HIFU

Table 4. PSA levels significantly decreased after HIFU

Pre-HIFU 3 months 6 months 9 months 12 months 24 months 36 months

Whole 4.92 + 5.73 1.14 + 1.58 1.59 + 1.84 2.04 + 2.29 2.45 + 2.73 2.84 + 3.42 2.07 + 1.76
Focal 5.36 + 5.89 2.74 + 3.37 3.17 + 3.70 3.37 + 2.79 3.14 + 2.64 3.42 + 2.67 1.52 + 0.92
P value 0.7539 0.0134 0.0258 0.0838 0.3622 0.6673 0.5305

Table 5. Urinary symptoms, testosterone and uroflowmetery scores before

and after HIFU

Whole Focal P value

IPSS
Pre-HIFU 8.58 + 7.14 10.20 + 6.14 0.3737
6 months 6.50 + 7.00 10.21 + 7.11 0.1935

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12 months 8.13 + 5.50 9.25 + 7.29 0.6827
Urinary bother
Pre-HIFU 81.25 + 18.85 84.38 + 12.94 0.6884
6 months 89.29 + 18.90 75.00 + 31.62 0.2220
12 months 85.71 + 24.40 80.00 + 20.92 0.6812
Urinary function
Pre-HIFU 88.62 + 18.30 83.33 + 16.64 0.5202
6 months 88.57 + 20.72 86.10 + 17.63 0.8021
12 months 87.21 + 11.42 86.04 + 20.83 0.9019
T
Pre-HIFU 378.23 + 141.62 454.54 + 171.58 0.1481
6 months 312.64 + 91.65 465.69 + 154.77 0.0006
12 months 262.13 + 151.37 488.11 + 186.10 0.0002
Maximal flow rate
Pre-HIFU 16.76 + 6.87 15.29 + 6.82 0.5126
6 months 15.31 + 8.74 15.48 + 6.82 0.9421
12 months 12.77 + 7.09 11.98 + 5.78 0.7711
Average flow rate
Pre-HIFU 9.17 + 3.38 7.70 + 4.46 0.2766
6 months 8.58 + 5.54 8.26 + 3.70 0.8269
12 months 7.38 + 4.36 6.90 + 3.59 0.7756

T, testosterone; IPSS, International Prostate Symptom Score questionnaires.

Figure 2. (a) Kaplan – Meier biochemical disease-free survival (DFS)

curves according to risk group. (b) Kaplan – Meier biochemical DFS curves
in the treatment of low-risk group. Biochemical DFS did not differ between
the whole and focal therapy groups. (c) Kaplan – Meier biochemical DFS
curves in the treatment of intermediate-risk group. Biochemical DFS did not
differ between the whole and focal therapy groups. M, months.
DISCUSSION
The treatment efficacies of the some modalities to localized
prostate cancer are different by a risk category. For low-risk
disease, all of the currently available treatment modalities
(i.e. radical prostatectomy (21,22), cryoablation (23,24),
brachytherapy (21,25), three-dimensional conformational
radiotherapy (26) and external-beam radiotherapy (21,27))
achieve excellent local and systemic control. Although the
follow-up periods are short, HIFU, in this study, achieved
excellent biochemical control for low-risk disease. When
compared with the results for low-risk patients, more uncer-
tainty arises in determining the optimal approach for patients
with intermediate- and high-risk disease. Despite treatment,
a significant proportion of these men will experience
PSA-defined failure and cancer-specific death. A drop in

efficacy can be observed for all therapies with increasing
disease risk (20 – 24,26,28 – 31). Correspondingly, in this
study, the 2-year biochemical DFS rates after HIFU in
patients at high risk were significantly inferior than those in
patients at low risk. Marberger (32) reported if an adequate
PSA nadir is not reached within 3 – 4 months, curative
therapy is probably failing and repeat HIFU or a change in
therapy should be considered. From our results, for patients
with intermediate-risk prostate cancer, combination therapy
of HIFU and other modalities (e.g. hormone therapy) should
be considered. But for patients with high-risk prostate
cancer, HIFU monotherapy did not result in satisfactory
cancer control.
Previous reports have shown that the negative biopsy rates
after HIFU treatment based on sextant core biopsies ranged
from 75 to 93% (8,9,11,15). In our study, since the time
series, post-HIFU PSA levels and positive rates at scheduled
biopsy did not differ significantly between patients who had
focal therapy and those who had whole therapy (Tables 3
and 4), cancer control with focal therapy could considered to
be equivalent to that of whole therapy. Although the median
follow-up time (34 months) was relatively short, neverthe-
less, these results suggest the efficacy of focal therapy.
However, restricting the region of ablation in the prostate is
not congruent with the traditional view that prostate cancer
usually manifests as a multifocal disease (17). Previous
attempts at prostatic lumpectomy with HIFU have so far
been impeded by the unreliable localization of the index
lesions (33). In 1995, Madersbacher et al. (34) treated 10
patients with T2a – b prostate cancer with one positive core
in a unilateral palpable nodule, with HIFU of the tumor-
bearing lobe only. Histologic evaluation after subsequent
radical prostatectomy showed that the tumor was always cor-
rectly targeted. However, because of unexpected tumor dis-
tribution, only 3 of the 10 patients’ tumors were completely
ablated. The conclusion from this at the time was that
because of the unpredictable tumor location the entire pros-
tate has to be always ablated. However, this report did not
clarify the way of clinical preoperative diagnostic criteria,
including prostate biopsy (e.g. how many cores, sextant or
more?) and imaging studies. Today’s advances in imaging
and biopsy techniques seem to permit more reliable detec-
tion of index cancers. Especially by the increasing number
of multi-regional biopsies more than 12 cores such as
adopted in this study, the cancer distribution is now more
accurately diagnosed (35). In the current study, the majority
of cancer treated was staged as T1C. By providing focal
therapy, it was possible that the treatment missed the transi-
tional zone cancer in the ipsilateral side. However, transition
zone cancers in stage T1c tumors, if any, have a favorable
pathology (36). Thus, there may be a little chance that focal
therapy missed the treatment of significant cancer. Indeed,
the incidence of new cancer lesion in the follow-up biopsies
was small in this study (data not shown).
Recently, Carroll et al. (37) have identified three potential
clinical parameters (lower stage, the number of positive
Jpn J Clin Oncol 2008;38(3) 197
biopsy core at diagnosis and prostate volume) that correlate
with unifocal disease. The use of some parameters to corre-
late with unifocal disease may need to establish the focal
therapy to localized prostate cancer.
In our results, the total volume and the transitional zone
volume of the prostate were not changed after focal therapy
in spite of decreasing PSA levels. Sequential anatomical
imaging showed that a gradual shrinkage of treated volumes
occurred by the whole therapy, which indicates the replace-
ment of the necrotic region with fibrous scar tissue. A pre-
vious report showed the size of the gland decreased after
HIFU to a 41% of the initial size (8). Since the contralateral
transitional zone was not ablated in focal therapy group,
these areas might have been spared for the circulation, and
hence, maintained its size.
It is still debatable whether PSA is the adequate measure
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to define the recurrence.
Although Uchida et al. (38) reported that there was an
association between the PSA nadir and the risk of treatment
failure after HIFU, our data showed no correlation between
PSA nadir and oncological results (data not shown). During
HIFU treatment, the temperature at the ablative focus can
rise rapidly to .80ºC, and this should lead to effective cell
destruction. This increase in tissue temperature depends on
the emitted mechanical energy and the absorbance of the
specific tissue. DPSA may reflect the extent that HIFU
injures the prostate parenchyma. Our results might indicate
that DPSA could be used as a predictor for successful
treatment.
If the entire prostate is not ablated, morbidity could be
reduced. Regarding the voiding function and QOL, there was
no difference between the focal and the whole therapies
(Table 5). However, the period of indwelling urethral cath-
eter after HIFU was significantly decreased in focal therapy
group compared with the patients in whole therapy group.
Clearly, the toxicity and results of HIFU depend on the
volume of prostate treated. If cancer volume is low and only
the cancer-bearing part of the prostate is treated, morbidity is
minimized: this is the theory behind focal therapy (32).
Considering that previously reported HIFU causes urinary
stricture in high frequency and needs transurethral resection
as an adjunct therapy at many institutions (39), focal therapy
may be useful for maintaining normal urination after HIFU.
Moreover, whole therapy, but not focal therapy, without
neoadjuvant hormone therapy decreased the serum testoster-
one levels. The magnitude of the changes in the androgen
levels may not have a direct influence on cancer control.
However, several results fit into a growing body of data,
suggesting that the persistent decline in the androgen levels
may have an impact on the QOL of the patients’ by influen-
cing their mood, physical abilities and sexual function (40).
Sarosdy et al. (41) even propose that testosterone-replace-
ment therapy after prostate brachytherapy treatment for early-
stage prostate cancer can be performed safely in selected and
carefully monitored patients. Thus, when focal therapy
results in cancer control equivalent to that of whole therapy,
198 Treatment of localized CaP with HIFU
it might be beneficial since it can maintain testosterone
level. It has been known that the radiation therapy for pros-
tate cancer causes a transient decline in serum testosterone
levels (42). This decline in testosterone levels after radiation
has been attributed to the scatter effect of the radiation on
the testis. However, since whole but not focal therapy with
HIFU affected the serum androgen levels, this decline in
serum androgen levels might not represent damage to the
testis, but rather indicate that the destruction of a large
number of prostatic cells could have a negative feedback on
testicular function. To our knowledge, this is the first report
about the effect of whole, but not focal, therapy on the
serum testosterone level. It still needs to be determined
whether the decreased androgen levels seen in patients fol-
lowing whole therapy subsequently recover, as is seen fol-
lowing radiation therapy.
The limitation of this study is the small number of treated
patients and the short duration of the follow-up. Both focal
and whole therapy groups have shown that HIFU did not
affect the UCLA-PCI and IPSS scores. As a result, HIFU
can be considered to be a QOL-oriented therapy (43).
Currently, no definite image studies are available routinely
to circumvent biopsy to know the exact localization of the
prostate cancer. However, when modalities to identify the
localization of prostate cancer developed, the focal therapy
would possibly be a feasible way of choice in the treatment
of small-volume prostate cancer.
In conclusions, HIFU can be considered to be a feasible
minimally invasive therapy for low-risk of localized prostate
cancer. HIFU focal therapy was equivalent to whole therapy
with respect to the short-term efficacy of cancer control.
Furthermore, focal therapy maintained serum testosterone
levels.
Funding
Funding to pay the Open Access publication charges for this
article was provided by Shigeo Horie.
Conflict of interest statement
None declared.
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