Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5209_Библиотеки_им_академика_М_И_Перельмана.pdf
328
1. Transrectal ultrasound (TRUS)
K. J. Tay et al.
ing low-grade cancer could be safely monitored
on AS, thus sparing suitable men from the morbidity of radical treatment. Thus, there has been
increased interest in the utilization of FT to treat
localized low-to-intermediate risk PCa.
Today, there are many ablative modalities that
can be used to treat PCa. Among them, cryotherapy is the only FDA-approved ablation modality
to treat PCa that has been widely used for the past
three decades. Herein, we focus mainly on the
principles, mechanism of action, and technology
that underpin focal cryotherapy, as well as recent
contemporary outcomes.
Cryobiology andTechnological
Advances inCryotherapy
Cryotherapy refers to the use of controlled local
freezing to remove thermal heat and cause cellular death. The majority of initial cellular deaths
arises from the physical effects of intracellular
ice crystal formation that occurs initially at
approximately −10 to −15 °C and maximally at
−40 °C resulting in cell membrane rupture [12].
Extracellular ice removes water from cells that
are not completely destroyed, leading to an
abnormally high solute concentration.
Subsequently, during the thaw phase, microcirculatory failure negatively impacts the viability of
any surviving cells in which mitochondria-related
apoptotic pathways are activated [13].
The use of ice for treating inammation has
been known since the time of ancient Egyptians.
The rst recorded use of a salt-ice "frigoric"
solution to freeze cancers was described by
Arnott in 1850 [14]. Subsequent advances in
chemistry permitted the use of liquid oxygen and
then liquid nitrogen for treatment of supercial
organs. Delivery of freezing temperatures to
deep-seated organs only became possible when
Cooper and Lee designed the rst cryosurgical
probe in 1961 that comprised a dual-lumen cannula with a hollow tip allowing for circulation of
liquid nitrogen [15]. In 1974, Megalli et al.
reported the rst transperineal percutaneous
prostate cryotherapy procedure using such a
cryoprobe [16]. These early probes were large
and required prostate dilatation prior to place-
ment, and the entire procedure was monitored
with a nger in the rectum.
Modern prostate cryotherapy is vastly superior in terms of efciency, accuracy, and safety
compared to early efforts. The three key developments leading to modern cryotherapy since the
2000s are the development of imaging and cryoablation systems, including:
imaging-guidance.
2. Third-generation cryogenic systems utilizing
argon and ± helium gas for rapid cooling and
thawing.
3. Protective urethral warming catheters.
4. Thermocouple devices to ensure adequate
ablation in the target region
The development of a high-quality TRUS system has allowed cryosurgeons to harness a unique
quality of ice that has high acoustic impedance,
which results in reection of up to 99% of acoustic
signals producing a characteristic appearance [17].
Direct visualization of the edge of the ice ball
allows the operator to control the extent of cryoablation and ensure that a good margin is achieved
while avoiding the rectum, urethral sphincter, or
the neurovascular bundles if so desired.
Modern argon gas cryotherapy probes operate
on the Joule-Thompson effect, whereby rapidly
decompressing argon within the needle tip loses
heat quickly to a nadir temperature of −186
°C.These needles also exchange argon for helium
gas when the freeze phase has been completed,
resulting in a much faster thaw. Modern cryoprobes are smaller, easier to place, and through
variable ice length adjustment, allow the ice balls
to conform to the shape of the intended ablation
zone. Third, the urethral warming device protects
the urethral mucosa from necrosis [18, 19]. When
an effective warmer is used, the rates of incontinence and urinary retention are signicantly
reduced, and the use of a urethral warmer has
now become the standard of care in prostate
cryotherapy [20]. Additionally, thermocouples
ensure that a lethal temperature colder than −20
to −40 °C is achieved, while a safe temperature is
maintained in the urethral sphincter and
Denonvilliers’ fascia [21].
a
bc
de
fg
28 Focal Cryotherapy
329
Patterns ofAblation
The pattern of ablation depends on the size, number, and location of the index and satellite
lesion(s), with an adequate margin, typically
thought to be at least 5–10mm from the edge of
the known lesion [22]. Some of these ablation
types include:
1. Focal ablation: Image-guided targeted ablation of index lesion with a safety margin.
Fig. 28.1 Patterns of
focal cryoablation: (a)
Focal ablation; (b)
quadrant ablation—
posterior; (c) quadrant
ablation—anterior; (d)
Hemi-ablation—lateral;
(e) Hemi-ablation—
anterior; (f) Hockey
stick ablation; (g)
Subtotal ablation
2. Partial gland ablation (PGA):
(a) PGA is dened as image-guided regional
ablation procedures based on biopsy and/
or biopsy-proven imaging localization of
tumors. PGA templates do not necessarily
rely on image identication of tumors, but
instead utilize anatomic regions of ablation intended to preserve organ function
while achieving complete tumor treatment. The subtypes are depicted in
Fig.28.1.
330
K. J. Tay et al.
Cryotherapy asaFocal Therapy
Option
Cryotherapy is well suited for focal therapy for
several reasons:
1. The transperineal approach allows excellent
access to all regions of the prostate, including
the anterior zone, where 20–30% of PCa can
arise [23].
2. The variable-length cryoprobes allow the
shape of the ice ball to be adjusted to create
the desired ablation zone.
3. The extent of ablation can be monitored in
real-time under TRUS guidance, allowing the
operator precise control of margins.
4. The thermocouples allow real-time temperature monitoring of nearby vital structures
such as the urinary sphincter and neurovascular bundles, ensuring safety, while monitoring the ablation zone itself allows the
operator to be certain of lethal ablation
temperatures.
5. The use of the urethral warming device prevents urethral injury and reduces urinaryrelated complications compared to other
ablative modalities.
6. Finally, it is a minimally invasive, often painfree outpatient procedure and can be repeated
if necessary with low morbidity.
Focal Cryotherapy Procedure
Focal cryotherapy is usually performed in the
operating room under general or spinal anesthesia, although there have been reports of completing it under local anesthesia (Fig. 28.2). The
patient is placed in the lithotomy position. The
scrotum is elevated cephalad, exposing the
perineum and secured using adhesive tape. The
perineum is prepped and a biplanar TRUS probe,
mounted on the stepper, is introduced into the
rectum to visualize the prostate and measure its
dimensions. Cryoprobes are available in variable lengths and they are selected based on the
prostate and lesion size. They are placed into the
prostate through the perineum using a template
biopsy grid secured with the stepper under
TRUS guidance. Cryoprobes are then adjusted
to create the length of the ice balls according to
the lesion size. Cryoprobe positions are checked
on ultrasound in both transverse and sagittal
planes. Thermocouples are typically placed at
the external sphincter and Denonvillier’s fascia,
though additional probes may be placed at the
neurovascular bundles or at the margin of the
planned ablation zone as needed. A exible cystoscopy is then performed to verify that the
cryoprobes have not traversed the urethra. A
urethral warmer is placed over a super-stiff
guidewire. Freezing is performed under realtime ultrasound and temperature monitoring,
followed by an active thaw. Two freeze-thaw
cycles are typically performed to ensure complete cell kill within the ablation zone. The cryoprobes are removed after the nal thaw, and to
reduce the chance of perineal and scrotal bruising, manual pressure is applied to the perineum
until the bleeding from the puncture sites stops,
usually about 5 min. The urethral warmer is
exchanged for a Foley catheter that will usually
remain for several days to reduce the chance of
urinary retention due to edema, a sequela of
thermal ablation. The patient is usually discharged home on the same day.
ab
28 Focal Cryotherapy
d
c
331
e
Fig. 28.2 Focal cryoablation procedure. (a) The patient
is positioned in lithotomy, prepped, and draped. A biplanar ultrasound probe is inserted into the rectum, and a grid
is placed against the perineum. Both are mounted on a
stepper for stability and precision during the procedure.
(b) Left Hemi-ablation pattern is being used here with
cryoprobes placed in the left hemi-gland. (c) Conrmation
of cryoprobe placement before freezing is veried by
ultrasound in the axial view. The arrow points to the cryoprobe, identied by its hyperechoic appearance, situated
in the left hemi-gland. (d) Console readout depicting (1)
channel control: shows connected cryoprobes and thermosensors with set temperatures; (2) channel status: shows
active cryoprobes with its corresponding temperatures;
(3) temperature sensors: show active thermosensors with
its temperature; (4) organ mapping: shows positioning of
the cryoprobes. (e) The ultrasound image shows the growing ice ball (indicated by the white arrow) with the cryoprobes in place (highlighted by the red arrow) in a sagittal
view
332
K. J. Tay et al.
Contemporary Focal Cryotherapy Series
Focal cryotherapy was rst described by Onik
et al. in 1997 as a form of hemi-ablative treatment and since then has been the most widely
used modality for focal therapy in the United
States. There is much evidence in the literature
on the oncological and functional outcomes following focal cryotherapy.
Primary Focal Cryoablation
Tay etal. [24] and Kotamarti etal. [25] reviewed
contemporary cohort studies of prostate focal
cryotherapy between 2008 and 2023 (Table28.1).
Most studies used a hemi-ablation template with
a median follow-up of 6–85 months. The biopsy
criteria for patient selection prior to therapy and
posttreatment biopsy varied across studies. Also,
D’Amico risk groups were mixed, but most of the
patients treated with focal cryotherapy were of
low- and intermediate-risk groups. The biochemical progression-free survival (BPFS) rate dened
by the Phoenix criteria was 71–98%, with two
studies quoting 3-year BPFS from 56 to 62.5%
[35, 38] and two studies describing 5-year rates
from 62 to 70% [34, 36]. Among nine cohorts
that mandated re-biopsy between 6 and 12
months posttreatment, the positive biopsy rate
was 7.1–38.9%, a quarter of which were clinically signicant (csPCa). However, there is signicant heterogeneity in patient selection,
inclusion criteria, use of imaging, denition of
success, and surveillance among these studies.
Notably, in a recent prospective study involving 132 men diagnosed with intermediate-risk
PCa, partial gland cryoablation demonstrated
promising outcomes. The study reported a 3-year
freedom from recurrence for in-eld, out-ofeld, and overall csPCa at rates of 97%, 87%,
and 86%, respectively [48].
The reported posttreatment pad-free conti-
nence and potency rates were 95.1–100% and
46.8–100%, respectively. Complication rates
mentioned in the cohorts were all low, and highgrade Clavien-Dindo ≥3 complications did not
surpass 4% in any study. Urinary retention was
the most encountered adverse event likely related
to reactive edema and can generally be avoided
by maintaining a urethral catheter for a few
weeks. The urinary retention rates were recorded
at 0–9% post-focal cryoablation, and rectourethral stula was seen in up to 0.8% of patients
across all cohorts. Other reported complications
include hematuria, hematospermia, urethral
sloughing, and stricture, which are relatively
uncommon.
There are no comparative studies between
focal cryotherapy and established treatments
such as RP or RT.One study [34] compared partial to whole gland cryotherapy using a matched
pair analysis in patients with low-risk prostate
cancer in the Cryo-Online Data (COLD) registry.
No difference was observed in 60-month BPFS,
and the rates of erectile recovery were noted to be
signicantly better with partial ablation (68.8%
vs. 46.8%). A second study [36] used propensity
score matching to compare partial to whole gland
cryotherapy in patients with intermediate-risk
prostate cancer from the same registry. This study
reects a more contemporary approach to selecting focal cryoablation for patients with
intermediate- risk disease. There was no difference observed in early BPFS, and those receiving
partial ablation were 2.1 times as likely to recover
erectile function by 12 months compared to those
undergoing whole gland cryoablation (46.8% vs
29.5%, p = 0.001).
28 Focal Cryotherapy
333
(continued)
Sexual function
outcome Complications
Oncological
outcome
Median
follow-up
(months)
Follow-up
protocol
Ablation
plan
NR
90% of those
previously
potent retained
ability to
BPFS; 85%
absolute BPFS
(ASTRO);
54 92% 1year-
3 monthly
PSA for 2
years then 6
monthly
Hemi-
ablation
NR
penetrate
8.3% (outeld)
routine
1.9-point
decrease in
positive biopsy
biopsy at 12
(phoenix);
24 72.7% BPFS
months
3, 6-month
serum PSA
Hemi-
ablation
IIEF at 12
months
3.9% (ineld);
and 10.4%
(outeld)
positive biopsy
and 6
monthly after
12-core
TRUS if BCR
(phoenix)/
Rectal injury: 0%
74% had
ability to
penetrate at 1
year and 86%
and 15.1%
(outeld)
positive biopsy
44.4 1.4% (ineld)
positive DRE
3–6 monthly
PSA
6–12-month
TRUS then
Hemi-
ablation
Retention: 1.2%
Rectourethral stula:
0.1%
in 2.4 year
59% had
ability to
penetrate at 1
year
75.7%
yearly
NR NR 21.1 2-year BPFS
4% (1 retention
needing TURP), 1
UTI 4%
Rash 4% (1)
73% needed
assistance
No impotency
reported
(using nadir
+0.5); 7.7%
biopsy positive
19.1 88% BPFS
3 monthly
PSA for 2
years then 6
monthly
Triggered
Hemi-
ablation
TRUS bx if
PSA/DRE
abnormal
Declared
Table 28.1 Summary of published focal cryotherapy series
Final
demographic
Low risk: 23
(48%)
Int. risk: 18
inclusion
criteria
Unilateral
cancer
Pre-diagnostic
workup
(restaging
TMB after
48 TRUS biopsy
Author N
Onik etal.
2008 [26]
(38%)
High risk: 7
(14%)
2001)
Low risk: 44
(57%)
Int. risk: 31
cancer
77 TRUS Biopsy Unilateral
Trusdale
etal. 2010
[27]
(40.3%)
High risk: 2
(2.6%)
Low risk: 24
(33%)
Int. risk: 49
(67%)
Gleason 7 or
less
73 TRUS biopsy Unilateral,
Bahn etal.
2012 [28]
(47%)
Int. risk: 473
(41%)
1160 NR NR Low risk: 541
Ward etal.
2012 [29]
High risk: 143
(12%)
Low risk: 23
(88.5%)
Int. risk: 3
intermediate
risk
26 Staging TMB Low-
Hale etal.
2013 [30]
(11.5%)
334
K. J. Tay et al.
Sexual function
outcome Complications
Oncological
outcome
Median
follow-up
(months)
Follow-up
protocol
Ablation
plan
NR
No change in
IIEF at 24
months
(any post-op
increase);
19.4% positive
28 71% BPFS
PSA at 3, 6,
12, 18, 24
months
12 months
sectoral
ablation
biopsy
mandatory 12
core TRUS
biopsy
Retention 15%
Rectourethral stula
2%
Cavernous corpus
necrosis 2%
Urethral stenosis 2%
Mild reduction
in IIEF at 3
months then
back to
baseline at 6
months
(Phoenix);
12.5%
(ineld); and
14.6%
(outeld)
13.2 98% BPFS
3 monthly for
1st year then
6 monthly
PSA
12 core
TRUS
ablation
Retention 3.4%
76.9% of
those
positive biopsy
mandatory at
(phoenix);
63 95% BPFS
12 months
3 monthly for
1st year then
Hemi-
ablation
previously
potent retained
ability to
penetrate
4.9% (ineld);
and 12.2%
(outeld)
positive biopsy
6 monthly
PSA
12-core
TRUS biopsy
at 6–12
12 months: urinary
12 months:
months then
yearly/
triggered
continence: 100%;
urinary retention:
1.3%
63% had the
ability to
penetrate
71.3%
Final
Declared
inclusion
Pre-diagnostic
Table 28.1 (continued)
demographic
All low risk Targeted
criteria
cT1-T2b
Gleason 3 + 4
workup
62 TMB 40–85 years
Author N
Barqawi
etal. 2014
[31]
or less
Less than 50%
positive core
After TTMB,
<20% total
prostate, index
lesion <5 cc, 4
or less zones
All low risk Hemi-
involved
PSA <10
48 12 core
Durand
Positive cores
<33%
%core <50
staging TRUS
biopsy +
mpMRI
etal. 2014
[32]
Unilateral
Gleason 6 or
less
Low risk: 23
(56%)
Int. risk: 18
(44%)
Unilateral
cancer
PSA <20
1–2 cores
core biopsy
41 Minimum 12
Lian etal.
2015 [33]
<50%
involvement
Gleason 6–7
cT2b or less
All low risk Focal Reex biopsy 58.3 5 years BPFS:
≤6, PSA level
at diagnosis
<10 ng/mL,
and clinical
317 NR Gleason score
Mendez
etal. 2015
[34]
stage ≤T2a
28 Focal Cryotherapy
Sexual function
outcome Complications
NR NR
Oncological
outcome
56%
Median
follow-up
(months)
36.6 3 years BPFS:
Retention: 6.6%; No
RUF
12 months: Urinary
continence rate:
95.1%
46.8% had
ability to
penetrate
80.7%; 5-year:
70%
2.1% positive
NR NR
biopsy
83.2%
NR NR
62.5%
19 3-year BPFS:
EPIC-initial
reduction followed by
rise at 12 months
in IIEF score
which
recovered by 2
years
NR NR Mild reduction
NR NR
decline rate:
71.4% at 6
months. MRI:
6–12 months:
0 persistent
lesions
335
(continued)
Follow-up
protocol
PSA checks:
Ablation
plan
Hemi-
Final
demographic
Low: 85
Declared
inclusion
criteria
Pre-diagnostic
workup
163 NR Unilateral
year 1: every
3 months.
Then every 6
ablation
(52%),
intermediate:
67 (41%),
localized
disease
months
Partial NR 31 BPFS: 2-year:
high: 11 (7%)
Intermediate
(included
34.9% GGG1):
>10–20,
clinical stage
166 NR GGG2, PSA
Partial NR 25.2 BPFS: 2-year
166 (100%)
Low: 504
(60.9%),
T2b
disease
829 NR Localized
intermediate:
246 (29.7%),
high: 76
(9.2%)
Every 3
months for a
year, every 6
months
Hemi-
ablation
Low: 41
(39.4%),
intermediate:
53 (51%),
positive cores
<GGG4
104 NR Unilateral,
thereafter for
PSA and
digital rectal
exams
high: 8 (7.6%)
PSA at
3-month
intervals
Hemi-
ablation
3 +3: 37
(42.1%), 3+4:
39 (44.3%), 4
+ 3: 12
unilateral
disease, lack
of MRI ECE
88 NR PSA <10,
Targeted NR 6 Median PSA
(13.6%)
Intermediate: 5
(100%)
MRI visible,
targeted
biopsy-proven
biopsy
5 3-D mapping
GGG3
localized
disease
Author N
Kongnyuy
etal. 2017
[35]
Tay etal.
2017 [36]
Elshafei
etal. 2018
[37]
Kongnyuy
etal. 2018
[38]
Werneburg
etal. 2018
[39]
Inoue etal.
2019 [40]
336
Sexual function
outcome Complications
Oncological
outcome
Median
follow-up
(months)
7.1%, UTI: 3.2%,
stula: 0.8%,
hematospermia: 0.8%
Urinary retention:
5%, UTI: 9%, urinary
continence-100% at 6
84% of those
previously
potent retained
and 43%
(outeld)
27.8 57% (ineld)
months
ability to
penetrate
positive biopsy
3 years: FFS:
90.5%
NR
12 months:
mild reduction
in IIEF from
19.5 to 19
recurrence and
20% (outeld)
positive biopsy
15 No ineld
Dysuria: 2, UTI: 8
Mild reduction
in EPIC score
(ineld-54%
CS) and 17%
(outeld: 46%
CS) positive
biopsy
6 20%
NR
47 BCR: 25% 54% retained
Epididymitis: 2,
ability to
penetrate
Mild reduction
18 15% (ineld)
K. J. Tay et al.
urinary retention: 2
in EPIC score
and 4%
(outeld)
positive biopsy
Follow-up
protocol
Ablation
plan
Targeted NR 11 NR NR Urinary retention:
Final
demographic
3 + 3: 94
Declared
inclusion
criteria
Localized
Pre-diagnostic
workup
126 Systematic
mpMRI at 12
months;
Focal
ablation
(74.6%), 3 + 4:
31 (24.6%), 4
+ 3: 1 (0.8%)
3 + 3: 12
(9.8%), 3 + 4:
disease
and targeted
GGG: 2 or 3
or high
transperineal
biopsies
+ mpMRI
122 TRUS, TMB
biopsy after
BCR
89 (73%), 4 +
3: 19 (15.6%),
volume GGG1
(3 + 3)
mpMRI and
Focal
4 + 4: 2 (1.6%)
3 + 3:12
Anterior gland
17 Target and
targeted and
systematic
biopsy at 12
months
mpMRI and
ablation
(71%), 3 + 4: 2
(29%)
tumor
systematic
biopsy and/or
Focal
GGG >2 3 + 4: 32
TMB
55 MRI/TRUS
targeted and
systematic
biopsy at 6
months
ablation
(58.2), 4 + 3:
13 (23.6), 4 +
4: 7 (12.7),
4+5: 3 (5.5)
fusion target
and 12-core
systematic
biopsy
Biopsy after
BCR
mpMRI and
Hemi-
ablation
Hemi-
Low: 4 (15%)
intermediate:
22 (85%)
3 + 4: 40 (66),
Low-
intermediate
risk
Unilateral
and targeted
biopsy
26 Systematic
61 Systematic
targeted and
systematic
biopsy at 6
and 18
months
ablation
4 + 3: 15 (25),
4 + 4: 4 (9)
clinically
signicant GG
2 or higher
and targeted
MRI/US
fusion biopsy
Table 28.1 (continued)
Author N
Bakavicius
etal. 2019
[41]
Shah etal.
2019 [42]
Sze etal.
2019 [43]
Basourakos
etal. 2020
[44]
Bossier
etal. 2020
[45]
Chuang
etal. 2020
[46]
28 Focal Cryotherapy
337
(continued)
Sexual function
outcome Complications
Oncological
outcome
Median
follow-up
(months)
Follow-up
protocol
Ablation
plan
UTI: 28, RUF: 1
NR Urinary retention: 37,
and 19
(outeld)
positive biopsy
45 37% (ineld)
mpMRI at 1
and 12
months;
systematic
Focal
ablation
NR NR
6 7% (ineld)
core biopsy at
12 months
mpMRI and
Focal
positive biopsy
at 6 months
targeted +
ipsilateral
systematic
ablation
Urinary continence:
Ability to
NR 21.4% in-eld
biopsy at 6,
24, and 60
months
mpMRI at
Focal
100%
penetrate:
58%
positive
biopsy, PSA
decrease at 6
months, MRI
3–6 months,
12–24
months, and
5 years
ablation
Urinary continence:
96%, urinary
Mild increase
in IIEF-5
ability to
predict IFF
(34.6% in-eld
85 38.9% positive
mpMRI 3–12
months and
Focal
ablation
retention: 10,
hematuria: 6,
epididymitis: 7
and 36%
outeld
biopsy)
biopsy at 12
months or
earlier for
cause
Hematuria: 2 (2.6),
LUTS: 1 (1.3), UTI:
1 (1.3), perineal pain:
1 (1.3), testicular
swelling: 1 (1.3),
urinary retention: 1
in SHIM score
20 30.6% BCR Mild decrease
MRI and
control
biopsy at 12
months
Focal
ablation
(1.3), transient
incontinence: 3 (4)
Final
demographic
Low: 79 (66),
Declared
inclusion
criteria
Low or
Pre-diagnostic
workup
119 Systematic
Author N
Tourinho-
Intermediate:
40 (34)
intermediate
risk PCa
and targeted
transperineal
biopsy
Barbosa
etal. 2020
[47]
3 + 3: 9 (11%),
3 + 4: 51
(61%), 4 + 3:
23 (28%)
Unilateral GG
<4
and targeted
biopsy
83 Systematic
Wysock
etal. 2021
[48]
3 + 3: 30
(42.3) 3 + 4:
33 (46.5) 4 +
Low-
intermediate
PCa
targeted and
systematic
71 mpMRI +
Tan etal.
2021 [49]
3: 5 (7); 4 + 4:
2 (2.8) 4 + 5: 1
(1.4)
Low-Risk: 79
Low-
biopsy
121 mpMRI +
Marra etal.
(65.3)
Intermediate-
Risk: 40 (33.1)
High-Risk: 2
intermediate
PCa
targeted and
systematic
biopsy
2022 [50]
(1.7)
3 + 3: 4 (5.3) 3
+ 4: 44 (58.7)
4 + 3: 21 (28)
>2
75 NR Unilateral GG
Baskin etal.
2022 [51]
4 + 4: 4 (5.3)
GS9: 2 (2.7)