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Chapter27:Prostate ablations
are absorbed by tissues and converted to heat, inducing protein denaturation above 43°C.80 Second, US waves interact with
microbubbles in alternating cycles of compression and rarefaction, leading to inertial cavitation. Cavitation causes bubble
implosion and mechanical disruption of tissues at high intensities (>3500W/cm3). Violent dispersion of energy from cavitation can enhance tissue ablation,
81,82,83
though these eects
can be more dicult to control. Ablation specicity is possible
due to sharp energy drops outside the focal zone, preserving
the integrity of overlying and surrounding tissues. US or MR
guidance can be used for targeting and monitoring of thermal
damage in real time. HIFU ablations in the prostate mainly
use endorectal or transurethral transducers operating between
200kHz and 4MHz, delivering 100–10,000W/cm2 in the target region.
HIFU has a number of advantages relative to other thermal ablation techniques. Distinct advantages include its
non-invasive nature and lack of ionizing radiation. e procedure can be performed on an outpatient basis under spinal
or general anesthesia. e entire procedure typically takes
between 1 and 3 hours, depending on the size of the prostate
gland and operator experience. A 40-gram prostate can be
entirely treated in one session (Figure27.5, 27.6 and27.7).
Cryoablation
Cryoablation can be performed in the prostate with surgi-
84,85,86
cal,
nologic and imaging advances.
physical modication of tissue and cell destruction aer freezing below–30°C.89 Cryoablation devices typically exploit the
transrectal, or percutaneous approach due to tech-
87,88
Cryoablation is based on
Joule–ompson eect observed during expansion of pressurized gas. Ice-ball size can be tailored according to probe selection and gas ow rates. When cryoprobes are inserted into
Figure 27.4 Ultrasound-guided intensity focal ultrasound.
the prostate, an ice ball forms at the needle tip and this can be
imaged by US,87 CT (Figure27.8), or MR techniques to prevent undesired extension into surrounding tissues, the urinary
sphincter, or the rectum. Urethral warming catheters can be
used to avoid injury but warming could lead to undertreatment
of anteroseptal tumors.
Figure 27.5 Focal ultrasound
A
C
B
D
(US)-guided high-intensity focal ultrasound
ablation of a Gleason 6 (3 + 3) prostate
carcinoma (biopsies: 3 and 4 mm) in a
73-year-old patient with prostate-specific
antigen = 5.7 ng/mL. (A) T2-weighted
magnetic resonance (MR) image shows
a small tumor in the left basal peripheral
zone (arrow). (B) Corresponding
postcontrast T1-weighted MR image
showing enhancement of the tumor.
(C and D) Contrast-enhanced US images
performed at 1 month showing a complete
devascularization of the targeted zone.
Targeted biopsies showed no residual
tumor. (Courtesy of Professor Olivier
Rouvière, Dr. Gilles Pasticier, and Professor
Gregoire Robert.)
269
Section IX:Prostate
ABC
DEF
Figure 27.6 Subtotal ultrasound-guided high-intensity focal ultrasound ablation of a recurrence of Gleason 6 (3 + 3) prostate carcinoma in a 73-year-old
patient with prostate-specific antigen (PSA) = 0.68 ng/mL after radiotherapy performed 3 years ago (initial PSA = 4 ng/mL). Eight biopsies were positive in the
apex and bases. (A) T2-weighted magnetic resonance (MR) image shows a hypointensity in the left basal peripheral zone (arrow). (B) Corresponding postcontrast
T1-weighted MR image showed enhancement of the tumor (arrow). (C) T2-weighted MR image shows a hypointensity in the apex. (D) Corresponding postcontrast
T1-weighted MR image showed multifocal enhancements. (E and F) One-month MR follow-up showed subtotal devascularization of the prostate in the T1w
postcontrast images on the bases (E) and the apex (F). Healthy residual tissue may be observed (dashed arrows) due to the presence of the urinary catheter during
the procedure. (Courtesy of Professor Olivier Rouvière, Dr. Gilles Pasticier, and Professor Gregoire Robert.)
HIFU is mainly recommended for men with anteroposterior prostate diameter less than 40mm or volume under 40mL
without prostatic calcication.90 Limitations are similar to
those with diagnostic US, where sound waves do not pass readily through air or solid structures (e.g., calcications, catheters,
or brachytherapy seeds). Due to the accumulation of thermal
dose in the interposed tissue between transducer and focal
zone, special attention must be paid to overlying skin scars or
other tissue inhomogeneities. In addition, a transurethral or
suprapubic bladder catheter is recommended aer the procedure to maintain urinary ow during the postprocedure period
when edema is most pronounced. Depending upon the target
zone, one must consider that a catheter placed before the procedure may aect the ablation volume, oen in the anterior portion of the prostate (Figure27.6). Atemperature-monitoring
system is commonly used and can be particularly relevant for
transrectal approaches, where rectal stulas canoccur.
Other techniques
In addition to HIFU and cryoablation, several other techniques
have been used for focal prostate ablation. Photothermal ablation has been developed for prostate applications to a greater
degree than radiofrequency ablation, which is commonly
used in other organ systems.
91,92,93,94
Photothermal ablation
270
AB C
DEF
Chapter27:Prostate ablations
Figure 27.7 Focal ultrasound-guided high-intensity focal ultrasound ablation of a Gleason 6 (3 + 3) prostate carcinoma (biopsies: 3 and 3 mm) in a 65-year-old
patient with prostate-specific antigen = 5.14 ng/mL. (A) Postcontrast T1-weighted magnetic resonance image shows a small enhanced tumor in the right basal
peripheral zone (arrow). (B, C, and D) Corresponding apparent diffusion coefficient cartography and T2-weighted imaging (axial and coronal planes) showing the
tumor (arrow). (E and F) T2-weighted follow-up images performed at 1 year showing a scare (dashed arrow). Targeted biopsies showed no residual tumor. (Courtesy
of Philippe Puech.)
corresponds to the thermal destruction of cells by application of laser through optical bers inserted into the prostate. However, this technique is reserved for smaller discrete
tumors, because it is limited to an ablation zone with ±1cm of
maximal diameter.
Non-thermal ablation techniques have also been used in
the prostate, including irreversible electroporation and photodynamic therapy (PDT)95 (Figure27.9). Irreversible electroporation probes deliver ultrashort electrical pulses that disrupt cell
wall structure. is technique has shown promise in locations
where vascular heat-sink eects may occur with other ablation
modalities.96 Focal PDT causes cellular destruction aer systemic administration of a photosensitizing agent activated by
light within the prostate
97,98
(Figures27.10 and 27.11). e light
the rst week aer focal therapy for verication of treatment
67,68,69
eect.
ereaer, follow-up for the assessment of oncological control depends mainly on the experience of the treating teams. Several challenges exist. Firstly, no standardization
of imaging evaluation exists at this time. Secondly, PSA values
are dicult to interpret because a variable amount of prostate
tissue remains aer focal therapy as well as non-signicant
tumor tissue. It has been previously shown that several factors
inuence the postprocedural PSA, such as the ecacy of the
ablation therapy and the progression of benign prostate hyperplasia. erefore, the common methods to assess recurrence
employed aer radiation therapy have been used with ablation.
ey correspond to three consecutive rises in PSA from nadir
and/or nadir >2ng/dL.
99,100,101,102,103
source most commonly used is introduced through optical bers inserted into the target area of the prostate. Oxidative injury
has been observed aer PDT, which is thought to mediate direct cellular and local vascular damage. Studies on safety and
midterm outcomes are still limited for these two techniques.
Postprocedure evaluation
In order for focal ablation to be considered a viable option
for management of localized prostate cancer; the postprocedure surveillance requires standardization and research to
establish eectiveness to detect recurrent disease. In addition
to real-time monitoring performed during prostate ablation, US, contrast-enhanced US, or MRI can be used within
Complications and outcomes
Randomized trials to assess the comparative ecacy of each of
the ablation modalities described here are lacking. However,
several studies have separately reported complications or outcomes aer prostate ablation. In these studies, the choice of
ablation technique was based on characteristics of the prostate and cancer, as well as the experience with the technique or
availabilityofit.
Another major challenge in ablation of the prostate as
well as all therapy is the denition of what constitutes success and failure. As recommended in other organs, the Society
of Interventional Radiology criteria
104
may be used for the
271
Section IX:Prostate
AB C
DE F
Figure 27.8 Whole prostate salvage cryoablation of a T3b Gleason 8 (4 + 4) prostate carcinoma recurrence after radiotherapy in a 77-year-old patient with bone
metastases and prostate-specific antigen = 12 ng/mL. (A) T2-weighted magnetic resonance (MR) image shows a large tumor (arrow). (B and C) Four needles were
positioned into the prostate through a transgluteal way and under computed tomography guidance after carbodissection of the mesorectum. (D) Ice ball after
removing the needles. (E and F) Follow-up T2-weighted MR image and T1-weighted contrast-enhanced subtraction at 3 months showing the heterogeneous
ablative zone in T2w but without enhancement (discontinuous arrow).
description of prostate ablation. However, as prostate cancer
oen represents a slow-growing tumor and due to the selection of patients for these treatments, the use of conventional
disease-specic and overall survival could be challenging. To
obtain sucient event rates to prove non-inferiority of an ablation technique over radical whole-gland therapies in high-risk
patients or superiority over active surveillance in low-risk
patients could require large populations and long-term
follow-up of up to 10years. Moreover, although PSA outcomes are accepted as a valid outcome in standard therapies
such as prostatectomy or radiotherapy, the clinical utility of
PSA kinetics is still debated in focal prostate ablations due to
the expected residual presence of normal secreting residual
tissue as well as insignicant residual disease. Interestingly,
an imaging endpoint can be considered in future trials. e
MAPPED study, a 6-month randomized trial to evaluate the
eect of dutasteride on prostate cancer volume using MRI, is
the rst trial in localized prostate cancer to use imaging as a
primary endpoint.
105
Among all studies reported, median length of hospital stay
is 1day.
106
e incidences of the most frequent complications
(i.e., urinary retention, urinary stricture, and urinary tract
infection) range from 0% to 17%.
6,11,107,108,109
ese complication rates seem to be acceptable compared with the high incidence of complications related to radical treatment. Rabbani
etal. reported on 4,592 consecutive patients who underwent
radical prostatectomy without prior radiation or hormonal
therapy; median follow-up was 36.9 months (interquartile
range:20.3–60.6). ere were 11.4–23% minor complications
(grade 1–2 according to the Common Terminology Criteria for
Adverse Events (CTCAE) 3.0) and 5.3–6.6% major complications (grade 3–4).
110
272
AB
Figure 27.9 Focal irreversible
electroporation of a Gleason 7 (3 + 4)
prostate carcinoma (7 mm) in a
75-year-old patient with prostate-specific
antigen = 6 ng/mL. (A) Transrectal
ultrasound showing the needles on
the left side of the prostate (arrows).
(B) Needle positioning during
the ablation (1650–2850 V, pulse
length: 90 ms, number of pulses: 70).
(C) Finite-element treatment simulation
of the electric field strength according to
the anatomical structures and ablation
algorithm. (D) Follow-up T1-weighted
contrast-enhanced MR image at 3 months
showing no enhancement on the
C
D
ablative zone with outcome similar to the
modelization.
ABC
DEF
Figure 27.10 Focal vascular-targeted photodynamic therapy (WST11) of a Gleason 6 (3 + 3) prostate carcinoma in a 71-year-old patient with prostate-specific
antigen = 5.04 ng/mL. (A) T2-weighted magnetic resonance (MR) image shows a hypointensity in the right peripheral zone (arrow). (B and C) Corresponding
apparent diffusion coefficient cartography and postcontrast T1-weighted MR images showed the tumor (dashed arrow). (D) Three months postcontrast
T1-weighted MR image showed a devascularized zone. (E) Corresponding T2-weighted MR image. (F) Three-year MR follow-up showed only scar in the ablative
zone without recurrence. (Courtesy of Philippe Puech.)
273
Section IX:Prostate
AB C
DE F
Figure 27.11 Focal vascular targeted photodynamic therapy (WST11) of a Gleason 6 (3 + 3) prostate carcinoma in a 70-year-old patient with prostate-specific
antigen = 9.16 ng/mL. Two biopsies were positive in the right apex and right base. (A) T2-weighted magnetic resonance (MR) image shows a 23-mm hypointensity
in the left median peripheral zone (arrow). (B and C) Corresponding apparent diffusion coefficient cartography and postcontrast T1-weighted MR image showed
the tumor (arrow). (D) T2-weighted MR image performed 8 days after vascular-targeted photodynamic therapy shows a heterogeneous ablative zone (dashed
arrow). (E) Corresponding postcontrast T1-weighted MR image showed a devascularized zone. (F) One-year MR follow-up showed subtotal devascularization of the
prostate in the T1w postcontrast images. (Courtesy of Philippe Puech.)
A major potential advantage of prostate ablation is avoidance of injuries to neurovascular bundles as well as to surrounding organs if correctly targeted. Using validated questionnaires,
the pad-free continence rate varied between 95% and 100%
aer focal prostate ablation, and the range of leak-free rates was
83–100%. Considering only trials evaluating focal therapy with
intention to treat, when validated questionnaires were used,
erectile function sucient for penetration was reported in
54–100% of patients. Rectal toxicity was oen poorly reported.
When it was reported, rates of stula ranged from 0% to 1%,
but one series reported one of 41 men suering grade 3 rectal toxicity conservatively managed as a possible rectourethral
6
stula.
As no standardization of the techniques or comparative
(1.9%; both grade 3b). Most complications were grade 1, and
only one patient had a grade 2 complication.
Similar results have been reported by Ahmed etal. on 41 men
enrolled in a prospective development study of protocol-based
focal therapy using HIFU as dened by the IDEAL (Idea,
Development, Exploration, Assessment, and Long-term
follow-up) collaboration.6 ese treatments may involve <60%
of the prostate and edge of the treatment area is >10mm from
the neurovascular bundles. Regarding grade 1 and grade 2
complications, 9 patients (22%) had self-resolving dysuria, 7
patients (17%) had urinary tract infection, and 1 patient (2%)
had acute urinary retention. Agrade 3b complication occurred
in 1 man (2%), who had diarrhea and urethral stricture. No
patient presented any grade 4 or higher complication.
studies exist, it is at this time dicult to compare the tolerance
of each technique. However results are quite similar between
techniques but dependent on the approach (focal therapy vs.
hemi- or whole-gland ablation). In a cohort study of men with
low-risk prostate cancer who elected for focal therapy as the
primary treatment with dierent techniques (106 patients),
it has been shown that focal cryoablation was responsible for
most complications.11 However, in this study, the overall complication rate was only 13%, with only two major complications
Local control
At this time, no standardized imaging follow-up protocol has
been dened. A meta-analysis by Valerio et al.10 reported a
wide range of median follow-up in the literature from 17 to
47months in the studies reported, but only few studies had
a follow-up > 5 years. Tables 27.1 and 27.2 reported only
long-term results for the two most used focal therapies:cryoablation andHIFU.
274
Table 27.1 Outcomes of long-term studies af ter high-intensity focused ultrasound
Mean
Follow-up
Reference No. of patients Risk
Crouzet
et al., 2013
100
Ganzer
et al., 2013
114
El Fegoun
et al., 2011
108
Inoue
et al., 2011
115
Blana et al.,
116
2008
Blana et al.,
117
2008
PSA = prostate-specific antigen; US = ultrasound; bFS = biochemical-free survival; DSS = disease-specific survival; MFS = metastatic-free survival; NR = not reported; RFS = recurrence-free survival; OS = overall
survival; DFS = disease-free survival; M disease, metastatic disease.
1,002 Low
Intermediate
High
538 Low
Intermediate
High
12 Low
Intermediate
137 Low
Intermediate
High
163 Low
Intermediate
140 Low
Intermediate
(years) Intervention Guidance Major adverse eects
6.4 (0.2–13.9) Whole prostate US Incontinence: 3.1–6.4%
Bladder outlet
obstruction: 34.9–5.9%
8.1 (2.1–14) Hemiablation US Total: 28.3%
Incontinence: 16.9%
Fistula: 0.7%
10 Hemiablation US NR NR RFS: 5 years: 90%
36 months
4.8
(sd 1.2)
6.4 (1.1) Hemiablation US NR 0.16 bFS: 5 years: 77%
12–84
Hemiablation US Incontinence: 16/137
Dysuria: 33/137
Hemiablation US NR NR bFS: 5 years: 75%
nadirPSA
(ng/mL) Outcomes
0.14 bFS: 8 years: 76, 63, 57%
DSS: 10 years: 97%
MFS: 10 years: 94%
NR bDFS: 5 years: 88,
83, 48%
bDFS: 10 years: 71,
63, 32%
M disease: 0.4, 5.7,
15.4%
RFS: 10 years: 38%
OS: 10 years: 83%
DSS: 10 years: 100%
0.07 DFS: 5 years: 91, 81,
62%
DFS: 5 years: 66%
bFS: 7 years: 69%
DFS: 5 years: 66%
DFS: 7 years: 59%
newgenrtpdf
275
276
Table 27.2 Outcomes of long-term studies af ter cryoablation
Mean
Follow-up
(years) Intervention Technique Guidance
Transrectal US Potency
ablation
Major adverse
eects
impairment
Reference
Bahn et al.,
112
2012
No. of
patients Risk
73 Intermediate 3.7 (1–8.5) Focal
14%
Cheetham
et al., 2010
76 Low
118
10.1 (0.2–14.9) Whole prostate Transperineal US NR NR DSS: 10 years: 87%
Intermediate
High
Onik
et al., 2008
Bahn
et al., 2002
48 Low
119
590 Low
120
Intermediate
High
Intermediate
4.5 (2.8–10) Focal ablation Transperineal US Potency
inpairment
10%
5.43 Focal ablation Transperineal US NR NR bFS: 7 years: 61, 68, 61%
High
PSA = prostate-specific antigen; US = ultrasound; OS = overall survival; NR = not reported; DSS = disease-specific survival; bFS = biochemical-free survival; RFS = recurrence-free survival.
nadirPSA
(ng/mL) Outcomes
1.6 OS: 100%
NR bFS: 94%
newgenrtpdf
DSS: 100%
OS: 100%
RFS: 10 years: 38%
OS: 10 years: 83%
DSS: 10 years: 100%
Chapter27:Prostate ablations
Nevertheless, cancer-specic survival is extremely high
in all studies. It may be expected with the small numbers and
short follow-up inherent in almost all reported series, but also
may be related to the inclusion of many men with low-risk disease who have prolonged natural history. No man died of prostate cancer aer focal therapy in the dened follow-up period,
whereas four men died of other causes.
10
While outcomes may seem promising, residual tumors
oen persist aer prostate ablation due to the multifocal aspect
of the disease and the limitation of current detection techniques
of the prostate (i.e., biopsies or imaging). Whereas residual
disease was found in 73 of 74 men who had undergone subsequent radical prostatectomy aer ablation in six early series
performed to assess the safety of prostate ablations, residual
signicant cancer was only found in 0–17% of patients using
6,63,111,112
biopsy.
Moreover, when clinically insignicant cancer
also was taken into account, 4–50% of men had positive biopsy
results aer treatment (n=255). As explained above with the
concept of index lesion, these results must be balanced with the
therapeutic strategies used and well explained to the patient.
Moreover, these ndings as well as the persistence of normal
remaining prostate tissue also explain the diculty in using
PSA techniques aer prostate ablation. Patients may be advised
of this. Improvement of imaging follow-up must be achieved to
surpass this limitation.
Only few studies have compared radical prostatectomy
and prostate ablation. In a multi-institutional study, aer a
matched-pair comparison of focal cryotherapy and radical
prostatectomy, Bahn et al. showed a similar oncologic outcome (dened as salvage therapy-free survival)
112
for localized
low- and intermediate-risk prostate cancer. Aer a 3.7-year
follow-up, no patient developed metastasis ordied.
Although salvage treatment was given to 8–41% of patients,
and metastatic disease was diagnosed in 5–20%, overall survival
was 100% in the two series that reported this outcome.
111,112
Only 12 series reported the need for secondary focal treatments, with a range of 0–34%. Salvage local treatments were
reported in 14 series, with rates of 0–33%. One feasibility trial
with vascular-targeted photodynamic therapy had higher secondary focal (67%) and salvage treatment (83%).
113
As the
follow-up is oen short and as patients are oen adequately
selected, progression to metastatic disease is not described
in most studies to date, although it appears to be very low
(0–0.3%) when reported.
Acknowledgments
Authors thank for their contributions: Philippe Puech, MD,
PhD, radiologist, CHU de Lille, France; Olivier Rouvière, MD,
radiologist, Centre Hospitalier Universitaire de Lyon, France;
Yann Le Bras, MD, and Nicolas Grenier, MD, radiologists,
Gilles Pasticier, MD, and Gregoire Robert, MD, PhD, urologists, Centre Hospitalier Universitaire de Bordeaux, France;
Govindarajan Srimathveeravalli, PhD, Assistant Member,
Radiochemistry and Imaging Science Service, Department
of Radiology, Memorial Sloan Kettering Cancer Center,
NewYork, United States.
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