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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5209_Библиотеки_им_академика_М_И_Перельмана.pdf
Contributors
xxiii
Christopher Warlick Department of Urology, University of Minnesota,
Minneapolis, MN, USA
Priya N. Werahera Department of Pathology, University of Colorado
Anschutz Medical Campus, Aurora, CO, USA
Thomas M. Wheeler Department of Pathology & Immunology, Baylor
College of Medicine, Houston, TX, USA
ThomasR.Williams Smith Institute for Urology, Northwell Health, New
York, NY, USA
James S. Wysock Department of Urology, NYU Langone Health, NYU
School of Medicine, New York, NY, USA
Chi-Hang Yee SH Ho Urology Centre, Department of Surgery, Prince of
Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong
Kong, China
Alec Zhu Department of Urology, New York-Presbyterian Hospital/Weill
Cornell Medical Center, New York, NY, USA
Part I
Why Consider Focal Therapy?
Focal Therapy forProstate Cancer:
AGuide forPatients
KaeJackTay, EricS.Adams,
andThomasJ.Polascik
1
Introduction
Prostate cancer has been traditionally treated
with surgical removal or irradiation of the entire
prostate gland. While these techniques are effective at cancer treatment, they can damage the
delicate structures surrounding the prostate
responsible for urinary control and erectile function, resulting in long-term side effects and
reduced quality of life in prostate cancer survivors. In an effort to achieve cancer control and
yet minimize damage to these structures, the urological community has been exploring techniques
that treat the specic portion(s) of the prostate
where the cancer is located and actively monitoring the untreated portions of the prostate. This
approach is known as “focal therapy.1”.
1
Focal therapy: Cancer treatment where only the area(s)
of the organ where the cancer is located is treated.
K. J. Tay
Department of Urology, Singapore General Hospital,
Singapore City, Singapore
E. S. Adams
Department of Urology, Duke University Medical
Center, Durham, NC, USA
T. J. Polascik (*)
Duke Cancer Institute, Duke Prostate and Urological
Cancer Center, Durham, NC, USA
e-mail: thomas.polascik@duke.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
T. J. Polascik et al. (eds.), Imaging and Focal Therapy of Early Prostate Cancer,
https://doi.org/10.1007/978-3-031-66754-1_1
Focal therapy has become possible within the
past two decades due to advances in diagnostic
imaging and biopsies that localize the cancerous
parts of the prostate, as well as advances in treatment modalities that can focally target prostate
cancer treatment. If you are a good candidate for
focal therapy, this treatment strategy may allow
you to maintain a greater quality of life while still
providing control of your prostate cancer. This
strategy involves only treating the areas of the
prostate with aggressive cancer, so additional
treatments can be administered in the future if
new areas of aggressive cancer are identied. A
close follow-up regime is, therefore, necessary
after treatment to identify and treat any new or
remaining areas of aggressive cancer.
We believe that the best outcomes are achieved
when an appropriate treatment is matched to a
suitable patient based on individual circumstances and preferences. This chapter is written
to serve as a resource to aid you in making an
individualized treatment decision for your prostate cancer by helping you better understand the
concept of focal therapy including its benets,
possible side effects, and risks. For a more
detailed description of specic topics of interest,
please refer to the other chapters in this text. For
any specics regarding your personal health,
please consult your physician.
3
4
K. J. Tay et al.
Treatment Options forProstate
Cancer
Traditional Radical Therapies
Traditional treatment strategies for localized
prostate cancer,2 or cancer conned to the pros-
tate only, are based on treating the entire prostate
gland. These include surgical excision of the
whole prostate (radical prostatectomy), radia-
tion therapy of the whole prostate (delivered by
external beam radiation or implantation of radioactive seeds into the prostate [brachytherapy]),
or ablation of the whole prostate (using various
methods to kill prostate tissue including thermal
methods such as cryotherapy, high-intensity
focused ultrasound [HIFU] and lasers, or nonthermal methods such as electric pulses [irreversible electroporation]).
These whole-gland, radical strategies have
generally worked well in eliminating prostate
cancer within the prostate gland, but they are
often associated with collateral damage to adjacent tissues, causing long-term side effects. To
help you understand this better, a sketch of the
basic male anatomy is shown in Fig. 1.1. For
example, damage to the erectile nerves causes
reduced ability to have a penile erection, resulting in erectile dysfunction.3 Damage to the urinary sphincter may cause urinary leakage or
incontinence.4 Scarring to the urethra/urinary
passage causes stricture5 that may result in difculty in the passage of urine. Radiation can affect
the bladder (causing cystitis6) as well as the rectum (causing proctitis7), which can result in irritative symptoms and bleeding even years after
treatment.
2
Localized prostate cancer: Prostate cancer conned
within the prostate gland only, with no evidence of outward spread.
3
Erectile dusfunction: Difculty or inability to have an
erection of the penis.
4
Incontinence: Urinary leakage that cannot be controlled.
5
Stricture: Narrowing of the urinary passage, usually due
to scar tissue.
6
Cystitis: Irritation/inammation of the bladder.
7
Proctitis: Irritation of the rectum.
The recognition that these long-term side
effects have a signicant impact on the quality of
life of prostate cancer survivors has led the urological community to explore other, less morbid
ways of managing prostate cancer. One major
development has been the recognition that lowrisk8 prostate cancer tends to be slow- growing
and nonaggressive. Low-risk prostate cancers
and some intermediate-risk prostate cancers are
unlikely to impact a man’s lifespan, and this has
led to many calling for not treating these cancers
unless they grow or become more aggressive.
Low-risk prostate cancers and some intermediate-risk prostate cancers can be managed with
monitoring instead of active treatment. However,
this is complicated by the fact that a signicant
proportion of prostate cancers initially thought to
be low-risk are discovered later to be higher risk,
necessitating treatment in order to prevent cancer
growth and spread.
Active Surveillance
Active surveillance is an observation strategy of
carefully monitoring men with low-risk prostate
cancer with regular checkups using nger/digital
exam of the prostate, blood tests (such as prostatespecic antigen [PSA]), imaging scans, and/or
biopsies to periodically monitor the behavior of
their cancer. If cancer appears to be more aggressive during active surveillance, then surveillance
can be discontinued, and prostate cancer can be
treated. In published reports, approximately
50–70% of men remain treatment- free at 5years
of surveillance. The downside to this approach is
that frequent checks and biopsies are a healthcare
burden on the patient. Prostate imaging and biopsies have an associated cost, and biopsies are
associated with discomfort, anxiety, and potential
complications. There is still insufcient data and
experience to support a reduced frequency of
checks in men on active surveillance.
8
The D’Amico low-risk criteria consider those with a
prostate-specic antigen (PSA) <10, tumor involving less
than half of one lobe of the prostate gland, and a biopsy
Gleason score of 3+3 or less.
1 Focal Therapy forProstate Cancer: AGuide forPatients
5
Fig. 1.1 Anatomy of
the prostate and
surrounding structures in
(a) transverse view and
(b) side view
a
b
Focal Therapy forPrimary Treatment
Focal therapy refers to a strategy of treating only
the part(s) of the prostate gland that contains
aggressive cancer using a highly targeted energy
source such as cryotherapy (using very cold temperatures to freeze the tissue), HIFU (highintensity focused ultrasound that heats up the
tissue), lasers, or nonthermal methods such as
electric pulses (irreversible electroporation). Focal
therapy has become possible within the past two
decades due to advances in diagnostic imaging
and biopsies, which better localize prostate cancer,
as well as advances in treatment modalities that
can focally target prostate cancer treatment. This
strategy is generally only suitable if you have one
or two discrete areas of clinically signicant pros-
tate cancer. This allows your doctor to treat your
prostate cancer while minimizing the risk of collateral damage and reducing side effects, including
maintaining sexual and urinary function. These
techniques, however, are still being researched to
compare the long-term effectiveness of focal therapy with traditional treatment modalities. All
patients receiving both focal prostate cancer treatment and traditional radical prostate cancer treatment should have close monitoring for prostate
cancer persistence and recurrence. The treatment
strategy and modality you choose can inuence
the recommendations for your follow-up, but all
patients should have follow-up monitoring either
during surveillance or after treatment.
To take things one step further, your physician
may treat the area of aggressive cancer within the
6
K. J. Tay et al.
prostate while intentionally leaving areas of lowrisk, slow-growing prostate cancer untreated.
With this approach, the remaining untreated parts
of the prostate gland, including any areas of lowrisk prostate cancer, are placed on active surveillance and closely followed to ensure no additional
aggressive prostate cancer tumors develop. Focal
therapy is repeatable and can be applied to the
same part of the prostate gland if cancer recurs
and/or to other parts of the prostate gland if the
need arises during surveillance.
Focal Therapy forSalvage Treatment
Treating locally recurrent prostate cancer after
the failure of primary local treatment is called
“salvage” treatment and aims to treat the prostate
cancer while it is still localized and avoid the
need for systemic treatments such as hormonal
therapy and chemotherapy. After the failure of
primary treatment for prostate cancer, sometimes
focal therapy can be an option for salvage treatment of recurrent prostate cancer. For example,
for patients who have had prostate cancer treatment with radiation or ablation and have a recurrence of cancer in a well-dened portion of the
prostate, focal therapy can be used to target and
treat the localized recurrence of prostate cancer.
Salvage therapy using focal therapy may help
you avoid the need for hormonal therapy or chemotherapy, but you should understand that all
methods of salvage therapy carry more risks of
side effects than primary treatment because the
primary treatment already had an impact on the
prostate and surrounding tissues.
Determining if Focal Therapy Is
Suitable foryou
Why Consider Focal Therapy?
Focal therapy should be considered if you wish to
try to preserve your sexual and urinary function
while achieving control of your cancer using a
minimally invasive treatment. However, focal
therapy is a highly personalized approach that is
well suited for some, but not all, men. The following sections discuss some factors that you
should consider to help determine whether focal
therapy is a treatment strategy suitable for you.
Cancer Treatment Needs
The primary goal of prostate cancer treatment is
to eliminate any aggressive cancer within the
prostate. Therefore, it is rst important to determine whether your cancer can be sufciently
treated with focal therapy. In the past, all prostate
cancers were recommended for treatment, however, we now recognize that many low-risk prostate cancers pose little threat to your life and do
not require treatment. It is currently thought that
the majority of prostate cancer tumors are lowrisk and pose little threat to your health or life if
untreated. Conversely, a minority of prostate cancer tumors are high-risk, more aggressive, and
more likely to threaten your health or life if left
untreated. These latter tumors are called clini-
cally signicant cancers. It is thus essential to
map out the location of prostate cancer tumors
within the three-dimensional (3D) space of the
prostate with an emphasis on the identication
and localization of any aggressive prostate cancer
tumors.
The most important principle in order for
focal therapy of prostate cancer to be successful
is to get as accurate a cancer location map within
the prostate as possible so that prostate cancer
can be targeted appropriately. Fortunately,
advances over the past two decades in prostate
cancer mapping using imaging and biopsies have
made focal therapy for the treatment of prostate
cancer possible. Cancer mapping can be accomplished using biopsy with or without the help of
imaging. To date, there are two methods to identify and locate prostate cancers within the threedimensional prostate gland: multiparametric
magnetic resonance imaging (mpMRI) and threedimensional template mapping biopsy (3DTMB). Your physician may recommend either a
3D-TMB or mpMRI (sometimes both) to locate
your cancer and determine if you are a candidate
for focal therapy.
1 Focal Therapy forProstate Cancer: AGuide forPatients
7
Imaging
Multiparametric magnetic resonance imaging
(mpMRI) is the best imaging modality available
today for detecting and localizing prostate cancer
within the prostate gland. This imaging technique
preferentially detects larger and higher-risk prostate cancer tumors compared to low-grade prostate cancers. If there is suspicion of a potentially
cancerous area seen on your mpMRI, a targeted
biopsy will be recommended to obtain a sample
of the suspicious area to conrm whether it represents a prostate cancer tumor and to characterize
how aggressive the tumor is.
Biopsy oftheProstate
Standard 12-core template transrectal ultrasound biopsy (TRUS biopsy) is the typical type
of biopsy commonly used for the detection of
prostate cancer. However, this method of biopsy
alone is thought to be insufcient to precisely
localize your prostate cancer well enough for
focal therapy treatment planning. Increasing the
number of biopsy cores used to map out the prostate improves the detection and localization of
cancer, but it also increases the length of the
biopsy procedure and possibly the associated discomfort. Although the standard prostate biopsy
procedure with a template of 12 cores is usually
performed in the ofce setting, when mapping
biopsies are recommended, this is usually performed under general anesthesia with many more
biopsy cores.
Three-dimensional transperineal9 mapping
biopsy (3D-TMB) is a biopsy technique obtaining
anywhere from 40 to 80+ biopsies at close (5mm)
intervals using a grid to provide a 3D spatial map
of the location (using x, y, and z coordinates) of
each biopsy core. Although the number of biopsy
cores needed for this mapping depends on the size
of the prostate, this is usually performed under
9
Transperineal: Perineum refers to the skin between the
scrotum and anus. The transperineal biopsy procedure
thus has biopsies taken from the perineum and avoids
needles going through the rectum.
general anesthesia while you are asleep. This is
thought to be the gold standard for biopsy mapping of prostate cancer. While it is still possible
for this technique to miss a prostate cancer tumor
between these small (5mm) intervals, such a cancer tumor would likely be very small and unlikely
to be high-risk or clinically signicant.
Personal Preference
In traditional whole-gland treatment, there is a
moderate to high risk of damage to the neurovascular bundles containing your erectile nerves,
even when trying to preserve them (nerve- sparing
prostatectomy) (Fig. 1.1a). Focal therapy can
offer you a higher likelihood of preserving and
maintaining your current level of sexual function.
This is particularly the case if the area of your
prostate cancer is located at a distance from your
erectile nerves. However, sexual function carries
a different importance to every individual, so you
should consider your current and anticipated
future levels of sexual activity when deciding if
preservation of sexual function is an important
goal for you. For example, if you currently have
satisfying erections and sexual function, then
maintaining erectile function and sexual function
may be of great importance to you. On the other
hand, if you already struggle with erectile dysfunction, then preserving your current level of
sexual function may not be an important value to
you, and traditional whole- gland treatment may
be more aligned with your preferences.
Similarly, whole-gland prostate cancer treatment carries risks of causing post-treatment urinary leakage (incontinence) and narrowing of the
urinary passage (urethral stricture) due to damage to the urinary sphincter and/or urethra
(Fig. 1.1b). The urinary symptoms experienced
after prostate cancer treatments are usually the
worst in the short term, but these side effects can
be lifelong for many men. Focal therapy directed
to a specic portion of the prostate can reduce the
chances of these long-term side effects, especially if the area of focal therapy treatment is
relatively small and/or relatively distant from the
urethra and urinary sphincter.
8
K. J. Tay et al.
Mindset andPersonality
The goal of focal therapy is to treat your prostate
cancer while preserving your sexual and urinary
function by selectively treating the portion of
your prostate that has prostate cancer that needs
treatment. Because the goal is not to eradicate the
entire prostate, even after successful treatment, it
is possible for aggressive cancer to develop later
in untreated parts of your prostate gland. This
shares some similarities to radiation therapy in
which residual prostate tissue remains that can
later develop new prostate cancer tumors because
although the entire prostate gland is treated with
radiation, tumoral areas are preferentially killed
by the radiation. This is in contrast to surgical
radical prostatectomy, in which the entire prostate gland is removed entirely, offering a “onestep cure.” As such, close follow-up monitoring
is required after focal therapy, similar to patients
on active surveillance who do not receive cancer
treatment. Thus, focal treatment itself can be seen
as the rst step in the journey of managing prostate cancer, which will require further surveillance and may require additional treatment.
While we believe that better functional outcomes and fewer long-term side effects can be
achieved with a focal therapy strategy if you are a
good candidate, you should understand that this
treatment strategy requires continued careful follow-up surveillance after treatment. During surveillance after your focal therapy, it is possible
that additional prostate cancer treatments may
become recommended as your condition evolves.
Therefore, a focal therapy strategy may not be
well suited for you if you are low intolerance of
uncertainty, high in anxiety, and/or prioritize the
problem being “resolved” in a one-step fashion.
If these personality traits tend to describe you, an
individual might be better served with traditional
whole-gland treatment methods.
Summary: Factors toConsider
When Deciding if Focal Therapy Is
aGood Fit forYou
• Your PSA is less than 15.
• Your prostate cancer clinical stage is T1c or
T2a.
• Your prostate cancer appears to be clustered in
one area of the prostate on mpMRI, 3D-TMB,
or both.
• You understand and accept that the whole
prostate gland will not be treated.
• You understand the risk of undertreatment and
the potential need for further treatment.
• You understand the need for continued monitoring after focal therapy treatment.
• You value maximizing the preservation of urinary and sexual function.
Types ofAblative Technology
Available forFocal Therapy
While the concepts of focal therapy remain the same
for all types of ablative technology used, there are
several technologies available in current practice. All
of these technologies deliver targeted toxic therapy
to a certain focus of the prostate gland to kill the
tumor within that area while preserving surrounding
tissues. The technical details of the various types of
toxicity and how they can be delivered to the prostate are discussed in separate chapters of this book.
You should understand that the risks associated with
your treatment, including potential short-term and
long-term side effects, depend in part on the technology used. Research comparing these technologies is
ongoing, but these comparisons are challenging
because treatment risks are also inuenced by pretreatment risk factors and the specic size and location of prostate cancer being treated. Furthermore,
developments and improvements in technology have
1 Focal Therapy forProstate Cancer: AGuide forPatients
Table 1.1 Various technologies for focal therapy
Energy Energy type Delivery mode Guidance Commercial Example
Heat High-intensity focused
ultrasound
(HIFU) MRI InSightec
Laser Transperineal Ultrasound
Cold Cryotherapy Transperineal
Radiation Gamma radiation Extra-corporeal
Alpha radiation Transperineal seed
Nonthermal Irreversible
electroporation
Light
therapy
a
This list is not meant to be exhaustive
b
From outside the body
Photodynamic therapy Transperineal Ultrasound Tookad™
Transrectal Ultrasound Ablatherm™
Sonablate™
Transurethral Ultrasound TULSA™
MRI Visualase™
Transrectal Ultrasound, also
MRI
Ultrasound Endocare
needles
MRI
b
Surgically placed
gold markers
Ultrasound Seed brachytherapy
implants
Transperineal Ultrasound NanoKnife™
Galil/Boston Scientic
Stereotactic body radiation
therapy (SBRT)
9
a
continued to occur, making it challenging for
research studies to compare studies performed with
the latest advances. Therefore, although we can
compare treatment technologies, there is currently
insufcient evidence to conclude denitively on the
superiority of one technology over the others. In the
absence of stronger evidence that one technology for
focal therapy is better than the others, you should
discuss with your surgical team which method(s)
they have the most expertise with and which
method(s) would be best suited for your treatment.
Table1.1 summarizes these various techniques.
What toExpect During
theTreatment Process
The typical focal therapy procedure is an outpatient procedure, often performed while you are
asleep under general anesthesia. While the procedure is usually short (approximately 1+ hours in
duration), anesthesia has its own risks, even for
relatively short procedures. Therefore, standard
pre-anesthetic screening and workup may be performed by the anesthesia team. If you have other
signicant medical problems, these may necessitate optimization prior to your procedure. For
example, if you are on anticoagulants,10 these
may need to be stopped or adjusted surrounding
the time of your procedure under the direction of
your medical team.
Fasting for several hours is also usually
required prior to anesthesia, typically starting
from the night prior to the procedure. You may
also be required to undergo bowel preparation
with laxatives prior to your procedure, which will
be explained to you by your surgeon. Occasionally,
focal therapy may be performed under spinal
anesthesia or simply with a local nerve block.
This may be safer from an anesthetic standpoint,
but there would be a possibility that partial anesthesia is insufcient and must be converted to
general anesthesia. If electing anesthesia, the
anesthesiologist will meet with you to explain
these and other anesthetic considerations and
risks in detail.
During your treatment, you will be positioned
on the treatment table in a way that protects you
10
Anticoagulant: A blood-thinning medication.
10
K. J. Tay et al.
from injury from pressure, straining, or falling
but allows your surgeon to perform your treatment. The typical positions are lying on your side
for a transrectal treatment or lying on your back
with legs supported by stirrups for a transperineal
Fig. 1.2 (a) An
example of transrectal
treatment using a HIFU
probe. The treatment
beam passes through the
rectal wall to focus on
the prostate. (b) An
example of transperineal
treatment using a
cryotherapy probe. The
probe is placed through
the perineal skin, and
treatment is monitored
by the ultrasound probe
in the rectum
a
treatment. A targeting and/or imaging probe may
be placed in the rectum, and the ablative energy
will be delivered transrectally or transperineally
(Figs. 1.2 and 1.3). You may experience shortterm rectal discomfort after your procedure. If
b