Comparison of magnetic resonance imaging
and ultrasound (MRI-US) fusion-guided
prostate biopsies obtained from axial and
sagittal approaches
Cheng W. Hong*, Soroush Rais-Bahrami†, Annerleim Walton-Diaz†, Nabeel Shakir†,
Daniel Su†, Arvin K. George†, Maria J. Merino‡, Baris Turkbey§, Peter L. Choyke§,
Bradford J. Wood* and Peter A. Pinto*†
*Center for Interventional Oncology, Clinical Center, †Urologic Oncology Branch, ‡Laboratory of Pathology, and
Molecular Imaging Program, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, USA
§
Objective
To compare cancer detection rates and concordance between
magnetic resonance imaging and ultrasound (MRI-US)
fusion-guided prostate biopsy cores obtained from axial and
sagittal approaches.
Patients and Methods
Institutional records of MRI-US fusion-guided biopsy were
reviewed. Detection rates for all cancers, Gleason ≥3 + 4
cancers, and Gleason ≥4 + 3 cancers were computed.
Agreement between axial and sagittal cores for cancer
detection, and frequency where one was upgraded the other
was computed on a per-target and per-patient basis.
Results
In all, 893 encounters from 791 patients that underwent
MRI-US fusion-guided biopsy in 2007–2013 were reviewed,
yielding 4688 biopsy cores from 2344 targets for analysis. The
mean age and PSA level at each encounter was 61.8 years and
9.7 ng/mL (median 6.45 ng/mL). Detection rates for all
cancers, ≥3 + 4 cancers, and ≥4 + 3 cancers were 25.9%, 17.2%,
Introduction
Prostate cancer is the most common non-cutaneous cancer
in men in the USA with a lifetime risk of one in six, and is
the second leading cause of cancer-related mortality [1]. The
standard-of-care for diagnosing prostate cancer is the
systematic TRUS-guided biopsy, where 10–14 cores are
obtained from various anatomical sections of the prostate
[2–5]. Smaller and iso-echoic lesions are not visualised on
TRUS, and the overlap between benign and malignant
appearances means that prostate cancer remains the only
BJU Int 2015; 115: 772–779
wileyonlinelibrary.com
and 8.1% for axial cores, and 26.1%, 17.6%, and 8.6% for
sagittal cores. Per-target agreement was 88.6%, 93.0%, and
96.5%, respectively. On a per-target basis, the rates at which
one core upgraded or detected a cancer missed on the other
were 8.3% and 8.6% for axial and sagittal cores, respectively.
Even with the inclusion of systematic biopsies, omission of
axial or sagittal cores would have resulted in missed detection
or under-characterisation of cancer in 4.7% or 5.2% of
patients, respectively.
Conclusion
Cancer detection rates, Gleason scores, and core involvement
from axial and sagittal cores are similar, but significant cancer
may be missed if only one core is obtained for each target.
Discordance between axial and sagittal cores is greatest in
intermediate-risk scenarios, where obtaining multiple cores
may improve tissue characterisation.
Keywords
multiparametric MRI, fusion biopsy, prostate cancer
solid tumour where biopsy is not directed at particular
lesions [6].
MRI is the most sensitive imaging method for prostate cancer
because of its superior soft tissue resolution [7]. In addition,
imaging parameters on multi-parametric MRI (mpMRI) can
be used to estimate tumour aggressiveness and are correlated
with detection rates [8–10]. Although MRI can be directly
used to guide biopsy, it is time consuming, costly and
impractical because the patient occupies the MR gantry for the
whole duration of the procedure [11,12]. MRI-ultrasound
Published 2014. This article is a U.S. Government work and is in the public domain in the USA | doi:10.1111/bju.12871
MRI‐US fusion‐guided prostate biopsies: axial vs sagittal approaches
(US) fusion guidance has thus been developed to address these
issues [13]. It allows targeted biopsy of MRI-visible lesions in
the office setting, increasing cancer detection rates [10,14,15].
MRI-US fusion guidance has also been shown to be of
particular value in improving detection rates for men with
enlarged prostate glands or a history of prior negative biopsies
[16,17], where systematic biopsy historically has lower
detection rates. Even if cancer is detected on systematic
biopsy, MRI-US-fusion biopsy upgrades the Gleason score in
32% of patients, and thus, improves detection of clinically
significant cancers [18].
MRI-US fusion-guided biopsy is a rapidly growing field, with
at least three different companies offering competing products
[19]. Image registration between the volumetric MRI and
US imaging is achieved by semi-automated segmentation
and manual intra-procedural adjustment is necessary to
compensate for movement of the prostate. These fusion
guidance platforms allow biopsy in any imaging plane, with
the axial and sagittal approaches being the most common.
MRI-US fusion has been shown to improve detection of
clinically significant cancer with fewer cores compared with
standard biopsy [20]. However, in terms of the number of
fusion-guided cores to be obtained, as well as the imaging
plane to be used, optimal usage of these fusion guidance
platforms is not well-defined. In the present study, we
investigated the cancer detection rates and Gleason grades
obtained from biopsies from axial and sagittal approaches
using an end-fire biopsy probe.
Fig. 1 MRI registered with ultrasound visualized in the axial plane (a) and
sagittal plane (b). A biopsy target is located in the right apical mid area
of the prostate and visualized in red surrounded by blue. Needle
trajectory is shown by the red dots, and the orange line maps the biopsy
location for archiving and later use. Reproduced from Hong et al. 2014
[21].
(a)
(b)
Patients and Methods
A review of patients enrolled in a prospective trial assessing
MRI-US fusion-guided prostate biopsy with electromagnetic
tracking at the National Cancer Institute between August 2007
and June 2013 was performed (ClinicalTrials.gov identifier:
NCT00102544). All patients were enrolled in an Institutional
Review Board-approved clinical study with written informed
consent. Patients were referred to our institution for initial
evaluation, for clinical suspicion of prostate cancer despite a
history of prior negative prostate biopsies, or for diagnosed
low-grade disease that was not concordant with their high
PSA levels or PSA dynamics. All candidates underwent
standardised mpMRI, where suspicious lesions were identified
according to the previous National Institutes of Health (NIH)
validated scoring system and selected as targets for MRI-US
fusion-guided biopsy. This scoring system has been previously
validated to correlate with D’Amico risk stratification and
cancer detection rate [9,10]. Point targets were designated in
accordance to the planned biopsy location of the MRI-visible
lesions, in larger lesions where a single target was felt to be
inadequate for coverage; more than one biopsy target was
designated. In each patient, a combination of standard-of-care
12-core systematic biopsy and two MRI-US fusion-guided
biopsies (Fig. 1, one axial, one sagittal [21]) were obtained for
Published 2014. This article is a U.S. Government work and is in the public domain in the USA
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Hong et al.
each MRI-visible lesion. The MRI-US fusion-guidance
platforms used were research iterations of the now
commercially available UroNav system (Invivo, Gainesville, FL,
USA). Patients without MRI-visible lesions were not eligible
for the study and advised to follow-up with their referring
urologist for standard-of-care management.
MRI Acquisition and Interpretation
All images were acquired using a 3.0 T MRI scanner (Achieva,
Philips Healthcare, Cleveland, OH, USA) with a six or
16-channel body coil (SENSE, Philips Healthcare, Cleveland,
OH, USA) and an endorectal coil (BPX-30, Medrad,
Pittsburgh, PA, USA). Routine pre-contrast axial T1-weighted
imaging was done, and mpMRI consisted of triplanar
T2-weighted (T2W) imaging, diffusion-weighted (DW)
imaging generating apparent diffusion coefficient (ADC)
maps, axial three-dimensional fast-field-echo dynamic
contrast-enhanced MRI, and three-dimensional MRI
spectroscopy. mpMRIs were interpreted by two experienced
genitourinary radiologists (B.T. and P.L.C., with 6 and 13 years
of experience in prostate MRI, respectively). The criterion
for a suspicious area on T2W and DW imaging was a
well-circumscribed, round-ellipsoid, low-signal intensity
region within the prostate [22,23]. Each lesion found on MRI
was assigned a suspicion level based on the positive sequences
[9]. Biopsy targets designated in the seminal vesicles and based
on prior biopsy locations were not assigned a suspicion level.
During the procedure, a fan-shaped sweep of the prostate
using the US probe generated a volumetric US image [21].
Suspicious targets that were selected pre-procedurally were
displayed on the T2W imaging and fused with the real-time
TRUS image. The rigid registration was adjusted with
translation or rotation by the urologist or the interventional
radiologist. All pathological specimens obtained were
evaluated by a single experienced genitourinary pathologist
(M.J.M.).
Statistical Analysis
Statistical analysis was performed using JMP 9.0 (SAS
Institute, Cary, NC, USA). The detection rates for cancer
overall and for clinically significant cancers, as well as the
Gleason score, and the proportional cancer involvement for
positive cores was compared between axial and sagittal cores
using an unpaired analysis. Equivalence testing was performed
using the two one-sided tests (TOST) approach with a
maximum tolerable difference of 5%.
Paired analysis was also performed on a per-target basis.
Overall agreement and κ statistics were computed for the
detection of all cancers, for cancers ≥3 + 4, and for cancers ≥4
+ 3. The McNemar’s test was used to test for concordance on a
per-lesion basis. The percentage of cases where biopsy in one
imaging approach upgraded the Gleason score or detected a
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cancer that was missed on the other was calculated as well on
a per-biopsy target basis, as well as on a per patient basis with
the inclusion of systematic TRUS-biopsy cores. Among
sessions with ≥3 MRI-US-fusion targets, cancer detection rate,
percentage of cases where biopsies from one imaging
approach upgraded the overall Gleason score, and percentage
of cases where biopsies from the highest suspicion target(s)
upgraded the overall Gleason score were calculated. Detection
rates and rates of discordance were computed for the cohort
as stratified by prior biopsy status and MRI suspicion level.
Detection rates and rates of discordance were also computed
for sessions with only one MRI-US fusion target. Detection
rates and rates of discordance were computed for targets from
patients with a prostate volume of <40 mL and targets from
patients with a prostate volume of ≥40 mL.
After stratification by MRI suspicion level, the rates of
discordance were compared between the first half and second
half of our institutional experience using the two-tailed
Fisher’s exact test. Age, PSA level, prostate volume, race, prior
biopsy history, location of the lesion (anterior vs not anterior),
and MRI suspicion level were assessed as possible predictors
for discordance of cancer detection between axial and sagittal
cores using univariate logistic regression. Significant predictors
were then included in the multivariable logistic regression
analysis. A significance level of 0.05 was used for all statistical
testing.
Results
In all, 893 encounters from 791 patients who underwent
MRI-US fusion-guided biopsy between August 2007 and June
2013 were reviewed (Table 1). In all, 2690 targets were
biopsied under MRI-US-fusion guidance; however, 211 lesions
lacked the sagittal biopsy and 135 lesions lacked the axial
biopsy, and these biopsies were excluded from the analysis.
This yielded 4688 biopsy cores that were obtained from 2344
targets under MRI-US fusion guidance for analysis. The mean
age and PSA level was 61.8 years and 9.7 ng/mL (median
6.45 ng/mL). In all, 89.5% of patients had only one MRI-US
fusion-biopsy session.
Cancer detection rates overall and for clinically significant
cancers from axial and sagittal cores was statistically
equivalent (Table 2). Comparable Gleason scores and
percentage of core involvement were obtained when the
biopsy core was positive. However, the combination of both
cores which detected cancers in 31.7% of targets significantly
outperformed either the axial core (25.9%, P < 0.001) or the
sagittal core alone (26.1%, P < 0.001). Gleason ≥3 + 4 = 7 were
detected in 17.2% of axial cores and 17.6% of sagittal cores.
Gleason ≥4 + 3 = 7 were detected in 8.1% of axial cores and
8.6% of sagittal cores. However, the combination of cores
detected Gleason ≥3 + 4 = 7 and Gleason ≥4 + 3 = 7 cancers in
10.2% and 9.2% of targets, respectively.
Published 2014. This article is a U.S. Government work and is in the public domain in the USA
MRI‐US fusion‐guided prostate biopsies: axial vs sagittal approaches
For overall cancer detection, the agreement between the axial
and sagittal cores was 88.6% (κ 0.703, P < 0.001, Table 3a).
Considering only ≥3 + 4 = 7 cancers, agreement between axial
and sagittal cores was 93.0% (κ 0.769, P < 0.001, Table 3b),
respectively. When considering only ≥4 + 3 = 7 cancers,
agreement between axial and sagittal cores was 96.5% (κ
0.769, P < 0.001, Table 3c).
The addition of the axial core detected a cancer missed
by the sagittal core or upgraded the Gleason score in 8.3%
(195/2344) of targets. The addition of the sagittal core
detected a cancer missed by the axial core or upgraded the
Gleason score in 8.6% (202/2344) of targets.
On a per-patient basis without systematic biopsies, agreement
between axial and sagittal targeted cores for the detection of
Table 1 Characteristics of the study population.
Characteristic
Value
Total number of encounters
Mean (SD):
Age, years
PSA level, ng/dL
N (%):
Ethnicity:
White
Black
Other
Prior biopsy status:
no prior biopsy
positive prior biopsy
negative prior biopsy
Number of biopsy targets:
1
2
3
4
5
≥6
Number of biopsy sessions:
1
2
3
4
893
61.8 (7.7)
9.7 (14.8
706 (79.1)
138 (15.5)
49 (5.5)
168 (18.8)
352 (39.4)
373 (41.8)
163 (18.3)
218 (24.4)
241 (27.0)
150 (16.8)
68 (7.6)
53 (5.9)
708 (89.5)
66 (8.3)
15 (1.9)
2 (0.3)
cancer was 88.6% (791/893). Axial cores detected or upgraded
the Gleason score of cancer that would have been missed by
the combination of sagittal cores and systematic biopsy in
4.7% of patients (42/893). Sagittal cores did so for the
combination of axial cores and systematic biopsy in 5.2%
(46/893) of patients. Among the 512 encounters where ≥3
targets were biopsied, as suspicion level of the target with the
highest suspicion increased, cancer detection rate, as well as
the proportion of cases where fusion biopsies from either
approach upgraded the overall Gleason score increased
(Table 4). In sessions where the index target(s) were of
moderate or high suspicion, the highest Gleason score was
obtained only from MRI-US-fusion biopsies of the index
target(s) in 20.8% and 26.1% of cases respectively, and
upgraded the overall Gleason score.
In all, 24.4% (572/2344) of targets were from anterior lesions.
The mean prostate volume was 60.1 mL (median 51 mL). In
all, 29.2% (639/2344) targets were graded as low suspicion,
60.6% (1325/2344) targets as moderate suspicion, and 10.2%
(224/2344) targets as high suspicion. Stratified analyses of
per-target discordance were performed based on prior biopsy
status and MRI suspicion level (Table 5). Among each cohort
based on prior biopsy status, cancer detection rate increased
with higher MRI suspicion level (P < 0.001). High-suspicion
targets in patients with no prior biopsy had a very high cancer
detection rate of 90.4%, and discordance was lower than in
low- or moderate-suspicion targets. However, in patients with
a history of prior negative biopsies, discordance was lower
in low- and moderate-suspicion targets vs high-suspicion
targets. When considering only encounters with a single
MRI-US target, the rate of discordance was 9.5% among
moderate-suspicion targets (Table 6). Discordance was seen in
neither low-suspicion targets where axial and sagittal cores
were mostly both negative, nor high-suspicion targets where
in more than half of cases axial and sagittal cores were both
positive.
The cancer detection rate and rate of discordance was 44.3%
and 13.0% (637 targets) in prostates of <40 mL, and was 27.1%
Table 2 Unpaired comparison of detection rates for all cancers, ≥3 + 4 = 7 cancers, and ≥4 + 3 = 7
cancers, as well as Gleason scores obtained and cancer involvement between axial and sagittal
cores. Axial and sagittal cores are statistically equivalent for cancer detection (P < 0.001).
Outcome
Overall detection rate per-core
Detection rate for Gleason ≥3 + 4 = 7
Detection rate for Gleason ≥4 + 3 = 7
Detection rate for Gleason ≥4 + 4 = 8
Gleason scores obtained among positive cores:
3+3=6
3+4=7
4+3=7
≥4 + 4 = 8
Cancer involvement ≥50% when positive
Both, % (n/N)
Axial, % (n/N)
Sagittal, % (n/N)
31.7 (743/2344)
20.9 (490/2344)
10.2 (238/2344)
9.2 (216/2344)
25.9 (606/2344)
17.2 (403/2344)
8.1 (191/2344)
7.4 (174/2344)
26.1 (612/2344)
17.6 (413/2344)
8.6 (202/2344)
8.0 (187/2344)
34.1 (253/743)
33.9 (252/743)
3.0 (22/743)
29.1 (216/743)
46.7 (347/743)
33.5 (203/606)
35.0 (212/606)
2.8 (17/606)
28.7 (174/606)
44.6 (270/606)
32.5 (199/612)
34.5 (211/612)
2.5 (15/612)
30.6 (187/612)
42.6 (261/612)
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775
Hong et al.
Table 3 Paired comparison showing the level of concordance between axial and sagittal cores
obtained from the same lesion in detecting cancer overall (a), Gleason ≥3 + 4 = 7 cancers (b), and
Gleason ≥4 + 3 = 7 cancers (c).
(a)
Sagittal positive, % (n/N)
Sagittal negative,
% (n/N)
20.3 (475/2344)
5.8 (137/2344)
5.6 (131/2344)
68.3 (1601/2344)
Sagittal Gleason ≥3 + 4 = 7, % (n/N)
Sagittal negative or
Gleason <3 + 4 = 7,
% (n/N)
13.9 (326/2344)
3.3 (77/2344)
3.7 (87/2344)
79.1 (1854/2344)
Sagittal Gleason ≥4 + 3 =
7, % (n/N)
Sagittal negative or
Gleason <4 + 3 = 7,
% (n/N)
6.6 (155/2344)
2.0 (47/2344)
1.5 (36/2344)
89.8 (2106/2344)
Axial positive
Axial negative
(b)
Axial ≥3 + 4 = 7
Axial negative or <3 + 4 = 7
(c)
Axial Gleason ≥4 + 3 = 7
Axial negative or Gleason <4 + 3 = 7
Table 4 Per-patient analysis of encounters with ≥3 MRI-US fusion targets, stratified by MRI suspicion level. The proportion of cases where axial or sagittal
cores upgraded the overall Gleason score otherwise is shown, as well as the proportion of cases where the highest Gleason score was obtained only
from the highest suspicion target(s).
MRI suspicion
level
Low
Moderate
High
Number of
encounters
Cancer detection
rate, %
Axial cores upgraded
Gleason score, %
Sagittal cores upgraded
Gleason score, %
Highest suspicion
targets upgraded
Gleason score, %
62
356
92
51.6
65.2
85.9
3.2
5.3
10.9
3.2
7.3
6.5
8.1
20.8
26.1
Table 5 Subgroup analyses of per-target discordance between axial and sagittal cores. The population was stratified based on prior biopsy status and
MRI suspicion level.
Prior biopsy status
MRI suspicion level
No prior biopsy
Low
Moderate
High
Low
Moderate
High
Low
Moderate
High
Prior negative biopsy
Prior positive biopsy
Number of biopsy targets
Overall cancer detection
rate, %
Discordance, %
131
261
73
237
517
84
271
547
67
12.2
44.1
90.4
6.8
23.4
65.5
21.8
36.7
71.6
3.1
17.6
8.2
3.0
7.7
14.3
14.8
14.8
14.9
and 10.9% in prostates of ≥40 mL. Stratified by MRI suspicion
level, rates of discordance did not differ significantly between
the first half and second half of our institutional experience
(Table 7).
On univariate logistic regression, prostate volume, prior biopsy
status, and MRI suspicion level were significant predictors for
the presence/absence of discordant biopsy findings between
axial and sagittal cores (Table 8a). These three variables
remained significant on multivariable analysis (Table 8b).
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Discussion
Although fusion-guided biopsy is a rapidly growing field,
biopsy is currently performed with no standardisation of
either the number of cores or the imaging approach used.
The premise of MRI-US fusion guidance is to combine the
high resolution of MRI with the real-time capabilities of US.
This requires that a volumetric US image be obtained for
registration of the real-time TRUS with the previously
obtained diagnostic MRI study. Because US inherently
Published 2014. This article is a U.S. Government work and is in the public domain in the USA
MRI‐US fusion‐guided prostate biopsies: axial vs sagittal approaches
Table 6 Analysis of overall cancer detection rate and MRI-US fusion biopsy discordance between axial and sagittal cores in encounters with a single
MRI-US fusion target, stratified by MRI suspicion level.
MRI suspicion
level
Low
Moderate
High
Number of
encounters
Cancer detection
rate, %
Both fusion cores
negative, %
Both fusion cores
positive, %
Discordance, %
37
116
7
27.0
27.6
71.4
97.3
81.9
42.9
2.7
8.6
57.1
0
9.5
0
Table 7 Subgroup analyses of per-target discordance between axial and sagittal cores comparing results from the first half of the cohort to the second
half of the cohort, stratified by MRI suspicion level. P values are shown for significance testing of the difference in discordance (two-tailed Fisher's exact
test).
MRI suspicion
level
Institutional
experience
Low
First half
Second half
First half
Second half
First half
Second half
Moderate
High
Number of
biopsy targets
Overall cancer
detection rate, %
467
172
481
844
107
117
13.9
15.1
29.7
34.8
71.0
79.5
acquires a fan-shaped image (which can be axially or
sagittally oriented), when registering this to an MR image,
which is obtained as a series of parallel axial slices, a certain
level of distortion occurs. This is especially apparent near
the lowest apical portions and most lateral margins of the
prostate.
The manual adjustment by the biopsy team allows for added
accuracy in the registration of the MRI to the real-time TRUS
by slightly adjusting the automatic registration particularly
attending to the apical and lateral margins, which most often
require adjustments, especially in larger prostate glands.
However, improving the volumetric registration in one
two-dimensional imaging plane at a time may worsen the
registration in another, making perfect registration difficult to
achieve. In addition, imaging in the sagittal view is typically in
a lateral plane because the image at this plane is composed
almost entirely of peripheral zone. Movement of the prostate
can also adversely affect the quality of the registration in the
axis of movement, which may be difficult to predict. This
implies that for a given registration and set of biopsies, one
imaging approach may be more accurate than the other. The
results of the present study show that over a large number of
patients, there is no systematic difference that would favour
one approach over the other, suggesting this is difficult to
predict a priori. MRI is currently limited to identifying lesions
that are at ≥3 mm in diameter. Because the registration error
is estimated to be about 2.4 ± 1.2 mm [13], registration error
can affect cancer detection, and small foci of cancer may be
still missed by the MRI-US fusion-guided biopsy approach
[24].
Discordance,
%
P
7.3
9.9
12.1
12.9
11.2
13.7
0.32
0.67
0.69
Table 8 Univariate (a) and multivariable (b) logistic regression in
assessing various predictors for discordance of cancer detection
between axial and sagittal cores. Only significant variables on univariate
analysis were included in the multivariable analysis. Odds ratios (OR) and
P values are provided.
(a)
Age/year
PSA/ng/mL
Prostate volume/cc
Race
Prior biopsy result
Anterior lesion
MRI Suspicion
Univariate logistic
regression
White
Black
Other
None
Negative
Positive
No
Yes
Low
Moderate
High
(b)
Prostate volume/cc
Prior biopsy result
MRI Suspicion
OR
P
1.012
0.987
0.989
1 (reference)
1.193
0.795
1 (reference)
0.563
1.393
1 (reference)
0.991
1 (reference)
1.663
1.647
0.185
0.058
<0.001*
–
0.319
0.468
–
0.003*
0.073
–
0.952
–
0.002*
0.050
Multivariable logistic
regression
None
Negative
Positive
Low
Moderate
High
OR
P
0.992
1 (reference)
0.592
1.310
1 (reference)
1.670
1.719
0.004*
–
0.009*
0.115
–
0.036*
0.002*
Asterisks indicate P values less than 0.05.
Although biopsy outcomes from axial and sagittal approaches
are equivalent with about 90–95% agreement, obtaining
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777
Hong et al.
multiple cores can improve characterisation. The use of more
cores, either in the same plane or in different planes, may be
one way to increase the likelihood of overcoming registration
error, which may be most important for smaller lesions. These
results suggest that discordance among the axial and sagittal
core is highest when there is most uncertainty about the
pre-test expected biopsy result. High-suspicion targets in
high-risk patients are not likely to be discordant because it is
expected that both biopsy cores will yield cancer. However,
low-suspicion targets in low-risk patients are also not likely to
be discordant because it is expected that both biopsy cores will
be negative. It is intermediate-risk scenarios where uncertainty
and discordance is highest, where the use of multiple biopsy
cores can be particularly helpful. However, as per-core
detection rate is usually <50%, clinical scenarios where the
pre-test probability of a positive result is higher, such as
moderate or high suspicion on MRI, or a prior positive biopsy
result, will usually increase the odds of discordance where one
core is positive and the other is negative. Conversely, scenarios
where the pre-test probability of a positive result is lower, such
as low-suspicion MRI, larger prostate volumes that inherently
decrease cancer detection rate, or a prior negative biopsy
result, will usually decrease the odds of discordance, as it is
more likely both cores are negative [25–27]. Additional cores
are most helpful when there is most uncertainty of the
expected biopsy result, e.g. the scenario where clinical
parameters and imaging findings are in disagreement or
suggest intermediate risk. This was the case for most patients
in the present series. This finding is further supported by the
fact that in sessions with only one MRI-US fusion target
(eliminating the discordance that may occur from multiple
targets of differing suspicion levels in the same gland),
discordance was seen primarily in moderate-suspicion
targets.
Agreement is higher when considering only higher grade
cancers, but this is primarily due to more stringent criteria for
a ‘positive’ biopsy, and in this situation, a discordant result
implies potentially missing clinically important cancer. In
addition, obtaining only one biopsy core underestimates the
presence of cancer or its grade in about 8–9% of targets.
Even with the inclusion of systematic biopsies, this results in
under-characterisation or missed cancer in ≈5% of patients,
which is especially important in the setting of patient selection
for active surveillance [28,29]. Among patients with ≥3
MRI-US-fusion targets, if the index lesion(s) are of moderate
or high suspicion, the Gleason score obtained from fusion
biopsy of these target(s) upgraded the overall Gleason score in
20–26% of cases despite accounting for only a minority of the
biopsy cores. Thus, it is vital that the highest suspicion targets
be biopsied as accurately as possible.
The present study has several limitations, including its absence
of whole mount prostatectomy specimens as a ‘gold standard’
comparison. As biopsy locations were designated as point
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targets, lesion size could not be accounted for. A minority
of men had multiple biopsy sessions; however, due to the
comparative nature of the present analysis, the results of other
cores in each session served as an internal control, and their
inclusion increased our sample size and the strength of these
results. Results of the systematic TRUS biopsies were only
included for the per-patient analysis. However, each location
targeted for MRI-US biopsy represents different MRI-visible
targets that are suspicious for prostate cancer, and these
locations may have little correspondence to the anatomical
sextants where systematic TRUS biopsy is taken. Regardless,
given that MRI-US-fusion guidance has been reported to
improve detection rates of clinically significant cancer,
systematic biopsy should not be relied on to compensate for
cancers that are not detected on MRI-US-fusion technology. It
is also possible that the effect we see is simply due to the
addition of a second biopsy, and that two axial or two sagittal
biopsies rather than an axial and a sagittal biopsy would have
similar results. It is not possible to evaluate this scenario with
the present data. The present study is also affected by inherent
limitations of MRI-US-fusion guidance including endorectal
coil deformation and registration error, which would affect
clinical practice as well. Some of the men described in this
work have been reported in previous analyses from our group.
The heterogeneity of our patient population is a limitation as
well, which is addressed by various stratified and multivariable
analyses and our large sample size. Of note, the proportion of
high-suspicion targets in patients with a prior positive biopsy
is lower than the other two subgroups. This is explained by the
fact that if a prior positive biopsy has been documented,
high-grade cancer would probably have been referred for
definite treatment instead, leaving behind a cohort that is
more consistent with patients on active surveillance.
As significant procedural time is spent on patient preparation
and image registration, an increase in the number of cores
does not substantially increase the length of the procedure.
In addition, changing the imaging approach requires little
beyond rotation of the US probe, as the same anatomical
location is being biopsied, and has the potential to improve
biopsy coverage. In comparison to a single axial or sagittal
core, the second core detects a missed cancer or upgrades the
Gleason score in about 8–9% of lesions. This translated to a
clinically meaningful benefit in tissue characterisation in 5%
of patients in our present cohort. Although the absence of
whole mount pathology prevents definitive evaluation of the
accuracy of these MRI-US fusion-guided biopsies, it has been
shown that obtaining at least two cores helps to improve the
accuracy of pathological characterisation. As MRI-US-fusion
technology matures and becomes increasingly available efforts
will be directed towards establishing guidelines for its role
in cancer detection and clinical decision making. Further
long-term studies will better define the optimal usage of this
technology.
Published 2014. This article is a U.S. Government work and is in the public domain in the USA
MRI‐US fusion‐guided prostate biopsies: axial vs sagittal approaches
Conflict of Interest
NIH and Philips Healthcare have a cooperative research and
development agreement. NIH and Philips Healthcare share
intellectual property in the field. This work was supported by
the National Cancer Institute, the Center for Interventional
Oncology, and the Intramural Research Program of the NIH.
This research was made possible through the NIH Medical
Research Scholars Program, a public-private partnership
supported jointly by the NIH and generous contributions to
the Foundation for the NIH from Pfizer Inc., The Leona M
and Harry B. Helmsley Charitable Trust, and the Howard
Hughes Medical Institute, as well as other private donors.
For a complete list, please visit the Foundation website at
(http://www.fnih.org/work/programs-development/
medical-research-scholars-program).
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Correspondence: Peter A. Pinto, Urologic Oncology Branch,
National Cancer Institute, National Institutes of Health, 10
Center Drive, MSC 1210, Building 10, CRC, Rm 2W-5940,
Bethesda, MD 20892-1210, USA.
e-mail: pintop@mail.nih.gov
Abbreviations: ADC, apparent diffusion coefficient; DW,
diffusion-weighted; mpMRI, multi-parametric MRI; NIH,
National Institutes of Health; T2W, T2-weighted; US,
ultrasound/ultrasonography.
Published 2014. This article is a U.S. Government work and is in the public domain in the USA
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