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Balkan Military Medical Review
Oct - Dec 2013; 16(4): 441 - 448
Review Article
Contemporary Role of Transrectal Ultrasound - Guided Prostate Biopsy
Ioannis GALANAKIS1, Eleftherios AGIANNIOTAKIS2, Stylianos MEGREMIS3, Georgios
DELIMPASIS4, Konstantinos PSARAS5, Anastasios GIFTOPOULOS4, Konstantinos
PSILLAKIS6, Ioannis PETINARAKIS2, Ilias PALAIODIMOS7, Christos BISSIAS8*
Affiliation of the authors:
1. MD, PhD, FEBU, Department of Urology, Naval Hospital of Athens
2. MD, Department of Radiology, Sitia District General Hospital, Crete
3. MD, PhD, 1st Department of Radiology, Venizeleion Hospital, Crete
4. MD, Department of Radiology, 251 Hellenic AirForce Hospital, Athens
5. MD, Aegean Imaging, Rhodes
6. MD, 1st Department of Radiology, Venizeleion Hospital, Crete
7. MD, Department of Urology, Sitia District General Hospital, Crete
8. MD, 1st Department of Orthopaedics, Naval Hospital of Athens
Corresponding author:
Dr Ioannis GALANAKIS, MD, PhD, FEBU
Naval Hospital of Athens
Deinokratous Str, 70
11521 - Athens
Tel: 0030 210 7261333
E-mail: [email protected]
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Abstract
Prostate cancer is by far the most
common solid neoplasm in male
population, in Europe and USA,
nowadays. The only accurate method to
establish the diagnosis is the biopsy of
the prostate or the presence of cancer in
prostatectomy specimen. Prostate biopsy
is usually performed using transrectal
ultrasound (TRUS) which has gone
through various modifications over the
years and is considered now as the gold
standard for prostate biopsy. However,
a lot of unnecessary biopsies are
performed and a lot of insignificant
cancers are identified every day. "When
to biopsy" is a rather puzzling issue.
This article aims to review the current
indications and techniques of TRUS guided prostate biopsy.
Key words: prostate cancer, biopsy,
transrectal ultrasound
Introduction
Prostate
cancer
(PCa)
is
recognized, nowadays, as one of the most
important medical problems facing the
male population. In Europe, PCa is by far
the most common solid neoplasm with an
incidence rate of 214 cases per 1000 men
and it is the second most common cause of
death in men [1, 2].
The etiology of PCa is not well
known and many risk factors have been
studied; however only three of them have
been well-established: increasing age,
heredity (if one first-line relative has PCa,
the risk is doubled and if two or more firstline relatives are affected, the risk
increases by 5- to 11-fold), ethnic origin
(African and African Caribbean men are
three times more likely to develop prostate
Balkan Military Medical Review
Vol. 16, No 4, Oct - Dec 2013
cancer than white men of the same age) [1,
2].
Digital rectal examination (DRE),
Prostate-specific antigen (PSA) and
Transrectal Ultrasonography (TRUS) are
the main diagnostic tools to obtain
evidence of PCa and to perform, in
consequence, prostate biopsy which
definitely confirms the presence of cancer.
This article aims to review the
current indications and techniques of
TRUS-guided prostate biopsy.
Prostate Anatomy
The prostate gland (Fig. 1) is about
the size of a walnut and surrounds the neck
of a man’s bladder and urethra. It measures about 4 cm transversely at the base, 2 cm
in its antero-posterior diameter, and 3 cm
in its vertical diameter, with a mean
volume of 20ml. The prostate is
immediately enveloped by a thin but firm
fibrous capsule, distinct from that derived
from the fascia endopelvica and separated
from it by a plexus of veins. This capsule
firmly adheres to the prostate and is
structurally continuous with the stroma of
the gland.
Figure 1. Sagittal view of the prostate
Galanakis I. et al: Contemporary Role of Transrectal Ultrasound - Guided Prostate Biopsy
The prostate can be divided in two
ways: by zone or by lobe. McNeal was the
first to propose in 1968 that a prostate
consists of three zones: transitional,
central, peripheral and the anterior fibromuscular stroma [3], (Fig. 2). The zone
classification is most often used in
pathology while the lobe classification
(anterior, posterior, middle and lateral
lobes) is used in anatomy. Up to 70-80%
of prostatic cancers originate from the
peripheral zone, 10-20% from the
transitional and only 2.5% originate from
the central zone.
Figure 2. Schematic depiction of the transition
zone (TZ), central zone (CZ) and peripheral zone
(PZ) in transverse (A) and sagittal (B) planes. The
arrows represent the path of sextant biopsy needles
The seminal vesicles (SVs) are a
pair of small tubular glands located
posterior to the bladder and distal ureters.
The SV joins the distal portion of the vas
deference (VD) and becomes the
ejaculatory duct (ED), which drains into
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the prostatic urethra through the
verumontanum.
The arteries supplying the prostate
are derived from the internal pudendal,
inferior vesical and middle hemorrhoidal
artery. The prostatic venous plexus drains
into the internal iliac veins and
communicates with the vertebral plexus,
thereby allowing neoplastic spread to the
vertebrae. The lymphatics end mostly in
the internal iliac nodes, although some end
in the external iliac nodes. The nerves are
derived from the pelvic plexus.
Trus technique
There are several variations in the
technique of the TRUS-guided prostate
biopsy. We present here the most widely
accepted:
Patient preparation: fully informed
consent
that
outlines
alternatives,
consequences and complications of biopsy
is obtained prior to the procedure. A fiveday course of oral fluorokinolone is
required, starting the previous day. The
patient is advised to take a selfadministered cleansing enema (sodium
phosphate and dibasic sodium phosphate)
prior to the biopsy to eliminate gas and
remove feces. Patients on anticoagulation
therapy, aspirin or non-steroidal antiinflammatory (NSAIDS) agents are
advised to stop or adjust their treatment
depending on the agent.
Transrectal ultrasound: the patient
is positioned in the left lateral decubitus
position so as the probe can be inserted
more easily to the rectum. A topical
anesthetic ointment is applied to the index
finger prior to performing the DRE. A 5.0
to 7.5 mHz transducer is used for
transrectal imaging of the prostate. The
probe is gently advanced into the rectum
and transverse images are then obtained as
the probe is moved back from the base to
the apex. The volume of the prostate can
be calculated assuming that the gland is an
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ellipsoid. Thus, the formula for the
prostate’s volume is: (transverse diameter) × (cephalo-caudal diameter) × (anteriorposterior diameter) × (0.52).
The normal prostate gland has a
homogenous, uniform echo pattern. The
most common finding of prostate cancer in
TRUS is a hypoechoic area in the
peripheral zone with a sensitivity of 82%,
specificity of 24%, positive predictive
value of 23%, negative predictive value of
88% and overall accuracy of 40% (Fig. 3).
The prevalence of isoechoic or nearly
invisible prostate cancers on TRUS ranges
from 22 to 38%. European Association of
Urology (EAU) guidelines recommend not
to replace systematic with targeted
biopsies of suspect areas [4]. However,
additional biopsies of suspect areas may be
useful [16].
Figure 3. Transrectal ultrasonography. Top image,
solid white arrow depicts hypoechoic lesion within
the peripheral zone concerning prostate cancer.
Lower image depicts hypervascular area seen with
color Doppler imaging, yellow and red area
corresponds to the hypoechoic area seen on the
grayscale ultrasonography above.
Biopsy technique: An 18-gauge
biopsy needle loaded in a spring-action
Balkan Military Medical Review
Vol. 16, No 4, Oct - Dec 2013
automatic biopsy device is commonly used
to procure multiple 1.5cm prostate biopsy
specimens. The sextant biopsies scheme
from the mid lobe (parasagittal) of each
side of the prostate at the apex, middle, and
base, proposed by Hodge et al, was the
standard of care for many years [5], (Fig.
2). However, it was the time when most
cancers were palpable on DRE. In the
current PSA era, most cancers are NOT!
Furthermore,
mapping
of
radical
prostatectomy specimens has shown that
the majority of non palpable lesions lie in
the far lateral peripheral zone of the
prostate, which is not routinely sampled by
the sextant technique. Many authors
evaluated various biopsy strategies with
extended sampling cores, however the
optimum has not yet been determined. The
EAU recommends: "Sextant biopsy is no
longer considered adequate. At a glandular
volume of 30-40 ml, at least eight cores
should be sampled. The British Prostate
Testing for Cancer and Treatment Study
has recommended 10 core biopsies. More
than 12 cores are not significantly more
conclusive" [4]. Larger prostate volumes
need an individualized core strategy. A
recommended scheme for initial prostate
biopsy is shown on Fig. 4.
Galanakis I. et al: Contemporary Role of Transrectal Ultrasound - Guided Prostate Biopsy
Figure 4. Recommended scheme for initial prostate
biopsy. A lateral and medial sextant pattern with 12
cores (extended) covers the entire peripheral zone
(PZ) of the prostate to maximise diagnosis of the
most frequent cancer located in the PZ.
Anesthesia for prostate biopsy: The
minimum is the application of rectal
lidocaine gel 2% for 10 min before the
procedure. This should be combined with a
diclofenac 100 mg suppository 1 hour
before biopsy. However, the EAU
recommends: "Ultrasound-guided periprostatic block is state-of-the-art. It does
not make any difference whether the depot
is apical or basal. Intrarectal instillation of
a local anesthetic is clearly inferior to periprostatic infiltration" [4]. 10–20 mls of
local anesthetic is adequate. For prostate
biopsies with high number of samples
(saturation biopsy), a spinal or general
anesthesia is useful.
General indications for prostate biopsy
A) Level of PSA
The first elevated PSA level should
not prompt an immediate biopsy. It needs
to be verified after a few weeks by the
same assay under standardized conditions
(no ejaculation and no manipulations, such
as
catheterization,
cystoscopy,
transurethral resection and no urinary tract
infections) [4].
There is no normal value for PSA;
25% of cancers are detected in the zone 04ng/ml. Stamey et al in 1987 found 5.5%
cancer in patients with PSA 4-10ng/ml and
normal DRE [6]. Recent studies found 2030%! It is widely accepted that
PSA>4ng/ml is a strong indication for a
biopsy. However, many experts suggest
that the cut-off should be 2.5ng/ml, taking
into consideration recent studies (Catalona,
Smith) who found raised prostate cancer
rates in the PSA zone of 2.5-4ng/ml, with
80% of them being aggressive! [7, 8]
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B) Positive DRE
Jewet et al found that 50% of
patients with a positive DRE have prostate
cancer. Schroder et al, however, showed in
1998 that DRE has low prognostic value
and since then the European Randomized
Study of Screening for Prostate Cancer
does not recommend DRE as a screening
tool [4]. Nevertheless, DRE remains a
routine examination in all centers!
C) High Grade Prostatic Intraepithelial
Neoplasia (HGPIN)
In earlier studies, 25-79% of
patients with HGPIN had prostate cancer
on repeat biopsy. More recent studies
though, where the extended core technique
was used, showed much lower results (2.54.3%). As a conclusion, HGPIN as an
isolated finding is no longer considered an
indication for repeat biopsy [9]. If PIN is
extensive (i.e. in multiple biopsy sites),
this could be a reason for early repeat
biopsy because the risk of subsequent PCa
is slightly increased [10].
D) Atypical Small Acinar Proliferation
(ASAP)
ASAP is a different entity than
HGPIN, rather aggressive, found in 0.523% in prostate biopsies. In the presence
of ASAP, a repeat biopsy will reveal
cancer in 36-49%! Iszkowski et al
proposed repeat biopsies with 3-12 months
intervals [11].
Relative Indications for Prostate Biopsy
A) Palpable abnormality or/and rising PSA
after definitive treatment
Many authors suggest that a
palpable abnormality or/and rising PSA
after
definitive
treatment
(radical
prostatectomy, radiotherapy, cryotherapy)
is a relative indication for a prostate biopsy
in order to exclude local recurrence.
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B) PSA elevation related to age
Oesterling et al evaluated 2119 healthy
men aged 40 to 79 years, in a prospective,
community-based study and concluded that
the serum PSA concentration is directly
correlated with patient age and prostatic
volume, the latter of which is also directly
related to age [12]. Thus, rather than rely
on a single reference range for men of all
age groups, it is more appropriate to have
age-specific reference ranges. These agespecific reference ranges have the potential
to make serum PSA a more discriminating
tumor marker for detecting clinically
significant cancers in older men
(increasing specificity) and to find more
potentially curable cancers in younger men
(increasing sensitivity):
 40 to 49 years — 0 to 2.5 ng/mL
 50 to 59 years — 0 to 3.5 ng/mL
 60 to 69 years — 0 to 4.5 ng/mL
 70 to 79 years — 0 to 6.5 ng/mL
C) PSA velocity
Some authors have suggested that
assessing changes in PSA over time (PSA
velocity) may improve the accuracy of
aggressive prostate cancer detection when
compared to a single measurement of PSA
alone [13]. It has been proposed that a PSA
rise of 0.75 ng/ml or greater may be related
to cancer in patients with a PSA between 4
and 10ng/ml, while a PSA velocity
threshold of 0.4ng/ml has been proposed
for younger men with baseline levels
<4ng/ml.
D) Free/total PSA ratio (f/t PSA)
The free/total PSA ratio (f/t PSA) is
used to stratify the risk of PCa for men
who have total PSA levels between 4 and
10ng/ml and a negative DRE. In a
prospective multicentre trial, PCa was
found on biopsy in 56% of men with f/t
PSA < 0.10, but in only 8% of men with f/t
PSA > 0.25 [4, 14]. Nevertheless, the
concept must be used with caution as
Balkan Military Medical Review
Vol. 16, No 4, Oct - Dec 2013
several pre-analytical and clinical factors
may influence the f/t PSA, e.g. instability
of free PSA, variable assay characteristics
and very large prostate size. For example,
free PSA is unstable at both 4°C and at room temperature. In addition, assay
characteristics may vary and concomitant
Benign Prostatic Hyperplasia (BPH) in
large prostates may result in a dilution
effect. Furthermore, f/t PSA is of no
clinical use in total serum PSA values > 10
ng/mL or during follow-up of patients with
known PCa [4, 15, 16].
E) PSA density
Less commonly agreed upon
recommendation for TRUS guided prostate
needle biopsy includes PSA density
(PSAD) > 0.15, which is a measure of the
amount of PSA relative to the overall
prostatic volume (PSA / Prostate Volume
in cubic centimeters).
It must be emphasized that there is
no consensus on using any of the PSA
modifications and none of them has been
shown in clinical trials to reduce the
number of unnecessary biopsies or
improve clinical outcomes. The total PSA
cutoff of 4.0 ng/ml has been the most
accepted standard because it balances the
trade-off between missing important
cancers at a curable stage and avoiding
both detection of clinically insignificant
disease and subjecting men to unnecessary
prostate biopsies. Ongoing efforts are
targeted at identifying new serum markers
that will have greater diagnostic accuracy
for prostate cancer, particularly for
aggressive tumors.
Special Considerations
Transition zone biopsy
Transition zone (TZ) sampling
during baseline biopsies provides a very
low detection rate and TZ sampling should
Galanakis I. et al: Contemporary Role of Transrectal Ultrasound - Guided Prostate Biopsy
therefore be confined to repeat biopsies
[4].
Seminal vesicle biopsy
Indications for SV (staging)
biopsies are poorly defined. At PSA levels
>15-20 ng/mL, the odds of tumor
involvement are 20-25%, but a biopsy is
only useful if the outcome will have a
decisive impact on treatment, i.e. if the
biopsy result rules out radical removal for
tumor involvement or radiotherapy with
intent to cure [4].
Saturation biopsy
The incidence of PCa detected by
saturation repeat biopsy (>20 cores) is
between 30% and 43% and depends on the
number of cores sampled during earlier
biopsies [4]. The high rate of urinary
retention (10%) is a drawback.
Transperineal biopsy
The standard of care to perform a
prostate biopsy is the transrectal approach.
However, some urologists prefer to use a
perineal approach with comparable cancer
detection rates. The prostate is accessed
with the tru-cut biopsy needle through a
small incision of the perineum about 2cm
above the anal verge with the ultrasound
probe in the perineum.
The ultrasound-guided perineal
approach is a useful alternative in special
situations, e.g. after rectal amputation.
Complications of prostate biopsy
TRUS-guided
prostate
needle
biopsy is generally a safe procedure. It is
associated with frequent minor (range 60%
to 79%) and rare major (range 0.4% to
4.3%) complications and the need for
hospitalization ranges from 0.4% to 3.4%.
Persistent hematuria is the most common
complication and occurs in 47.1% of
patients and typically lasts 3 to 7 days
following the biopsy. Other complications
447
of TRUS-guided prostate biopsy include:
vasovagal episodes (5.3%), dysouria
(9.1%), prostatitis (1.0%), hematospermia
(37.4%), rectal bleeding (8.3%), urinary
retention (0.2%), fever>38.5oC (0.8%).
Conclusions
Ferguson was the first to perform a
prostate
needle
biopsy
using
a
transperineal approach in 1930 while
Astraldi used a transrectal approach in
1937. However, it was in 1987 when an
ultrasound probe was used to optimize the
transrectal prostate biopsy. Since then, as
ultrasound technology has become more
refined, this technique has been described
as a superior method of performing a core
biopsy of the prostate.
The optimum regimen for the
diagnosis of prostate cancer remains to be
determined. The ideal place and number of
cores are not clear but recent data support
the use of extended biopsy schemes.
Moreover, the research on the indications
for initial or/and repeat biopsies is
ongoing, in an effort to lower the
morbidity and avoid unnecessary biopsies
while trying not to miss significant
cancers.
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