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084.fm — 12/1/06
Graser et al.
Per-Sextant Localization and
Staging of Prostate Cancer
Genitourinar y Imaging • Original Research
Per-Sextant Localization and
Staging of Prostate Cancer:
Correlation of Imaging Findings
with Whole-Mount Step
Section Histopathology
Anno Graser1,2
Andreas Heuck2
Bernhard Sommer2
Joerg Massmann1,3
Juergen Scheidler2
Maximillian Reiser1
Ullrich Mueller-Lisse1
Graser A, Heuck A, Sommer B, et al.
OBJECTIVE. The objective of our study was to determine the diagnostic accuracy and interobserver agreement of 1.5-T prostatic MRI for per-sextant tumor localization and staging of
prostate cancer as compared with whole-mount step section histopathology.
MATERIALS AND METHODS. Combined endorectal–pelvic phased-array prostatic
MRI scans obtained at 1.5 T of 106 patients with biopsy-proven prostate cancer who had undergone
radical prostatectomy with whole-mount step section histopathology within 28 days of MRI were
retrospectively analyzed by three independent abdominal radiologists (reviewers 1, 2, and 3). Sextants of the prostate (right and left base, middle, and apex) were evaluated for the presence of prostate cancer and extracapsular extension (ECE) using a 5-point confidence scale. Data were statistically analyzed using receiver operating characteristic (ROC) analysis. Interobserver variability was
assessed by kappa statistics. For calculation of sensitivity and specificity, data from the 5-point confidence scale were dichotomized into negative (score of 1–3) or positive (score of 4 or 5) findings.
RESULTS. Forty-one patients had ECE (tumor stage T3), and 65 patients had organ-confined
disease (stage T2). Of 636 prostatic sextants, 417 were positive for prostate cancer and 135 were positive for ECE at histopathology. For prostate cancer localization, ROC analysis yielded area under the
ROC curve (AUC) values ranging from 0.776 ± 0.023 (SD) to 0.832 ± 0.027. For the detection of
ECE, the AUC values ranged from 0.740 ± 0.054 to 0.812 ± 0.045. Interobserver agreement (κ)
ranged from 0.49 to 0.60 for prostate cancer localization and from 0.59 to 0.67 for the detection of ECE.
CONCLUSION. Using the sextant framework, independent observers reach similar accuracy with moderate to substantial agreement for the localization of prostate cancer and ECE
by means of MRI of the prostate.
rostate cancer is the most common
malignancy in men between their
sixth and ninth decades of life in
Western Europe and North America and is also a leading cause of cancer death
in men [1]. Previous research has shown that
MRI can be used to localize prostate cancer
within the prostate. Dividing the organ into sextants (right and left bases, middle gland, and
apex) facilitates reporting of MRI findings and
improves reproducibility [2–4]. Furthermore,
MRI has been used for follow-up of prostate
cancer after irradiation therapy [5], hormonal
ablation [6], and cryosurgery [7]. MRI is the
most exact staging technique in prostate cancer
imaging and can be used to determine the location of the tumor before biopsy [8, 9]. Tumor
localization within the prostate is the key requirement of MRI of the prostate. It has been
widely accepted that MRI of the prostate has an
improved accuracy for cancer detection when
an endorectal coil is applied [10, 11] and when
P
Keywords: genitourinary imaging, imaging–histopathology
correlation, MRI, oncologic imaging, prostate cancer
DOI:10.2214/AJR.06.0401
Received March 19, 2006; accepted after revision
June 28, 2006.
1Department
of Clinical Radiology, University of Munich,
Marchioninistrasse 15, Munich 81377, Germany.
Address correspondence to A. Graser.
2Radiologisches Zentrum Muenchen-Pasing, Munich,
Germany.
3Present address: Pathologie Lachnerstrasse, Munich,
Germany.
AJR 2007; 188:84–90
0361–803X/07/1881–84
© American Roentgen Ray Society
84
urogenital MRI specialists rather than body
MRI radiologists interpret the images [12],
whereas its accuracy decreases in the presence
of postbiopsy hemorrhage [13, 14]. In previously undiagnosed patients with suspicion of
prostate cancer, tumor localization may help to
target prostate biopsy [9, 15]. Tumor localization is required to define local tumor extent by
means of MRI. The local extent of prostate cancer, in turn, determines therapeutic options.
Interobserver agreement about the presence of prostate cancer was moderate in the
study by Scheidler et al. [2], which was based
on the analysis of prostatic sextants. Nonetheless, for follow-up studies with MRI of the
prostate before and during nonsurgical therapy, it is crucial that the systematic error of interpretation be minimized. By applying the
sextant scheme for prostate cancer and extracapsular extension (ECE) localization and
comparing those findings with whole-mount
step section histopathology results, we sought
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Per-Sextant Localization and Staging of Prostate Cancer
TABLE 1: MRI Protocol
Sequence
TR (ms)
TE (ms)
Matrix
Field of
View (mm)
No. of
Acquisitions
No. of
Slices
Slice
Thickness (mm)
Interslice
Gap (mm)
Axial T1-weighted
480
12
384 × 256
320 × 320
3
40
4
1
Axial T2-weighted
5,000
102
256 × 224
160 × 160
3
19–24
3
0
500
10
256 × 150
160 × 160
4
19–24
3
0
4,400
111
256 × 224
160 × 160
3
23–27
3
0
Axial T1-weighted
Coronal T2-weighted
to verify the diagnostic abilities of combined
endorectal–pelvic phased-array coil MRI of
the prostate. Furthermore, we aimed to quantify interobserver agreement of three independent abdominal radiologists for interpreting
MRI of the prostate.
These 106 patients (mean age ± SD, 63.0 ± 6.8
years) formed the study population. Patients underwent radical retropubic prostatectomy within 3
months of MRI of the prostate. The mean PSA value
was 11.5 ± 6.4 ng/mL (range, 3.1–73.0 ng/mL).
MR Sequences and Image Interpretation
Materials and Methods
Between April 1995 and December 2003, 890
MRI examinations of the prostate were performed
on a 1.5-T system (Signa, GE Healthcare) using
combined endorectal–pelvic phased-array surface
coils (MRInnervu Disposable Endorectal Coils,
Medrad Europe). The patients underwent prostatic
MRI at our institution for the diagnosis and staging
of prostate cancer.
Patients underwent digital rectal examination
before the endorectal coil was placed to exclude anorectal disease or injury that would prohibit placement or inflation of the endorectal coil balloon. Endorectal coil balloons were routinely filled with
80–100 cm3 of air and gently pulled back to ensure
complete coverage of the prostatic apex.
Patient Population
Patients were retrospectively identified either by
review of pertinent logbooks that contained data on
all examinations performed on the 1.5-T MRI scanner (scans obtained before September 30, 1998) or
by a computerized search of our radiology information system (RIS) (Medavis RIS, version 1.9, Medavis) using the internal code for this specific examination (examinations performed after October 1,
1998). A database containing all patient data with the
names and addresses of the referring urologists was
generated. Subsequently, all clinical data—including biopsy results, prostate-specific antigen (PSA)
values, results of digital rectal examinations, and histopathology reports—were obtained by one of the
authors. Thus, a total of 315 patients who underwent
MRI for local staging of biopsy-proven prostate cancer were identified, of which 186 patients subsequently underwent radical retropubic prostatectomy
for resection of prostate cancer.
For exact correlation of MR images with histopathology results, only the patients whose prostatectomy specimens were reviewed in a whole-mount
step fashion (n = 106) were included in this study.
AJR:188, January 2007
Sagittal, coronal, and axial localizer images
were obtained to check the position of the endorectal coil and to define the positions of subsequent
MRI sequences. Axial T2-weighted fast spin-echo
images covered the prostate and seminal vesicles.
Coronal T2-weighted fast spin-echo images of the
pelvis were centered on the prostate. Axial T1weighted spin-echo images covered the pelvis from
the iliac crest to the symphysis pubis to identify enlarged lymph nodes and bone lesions. A second axial T1-weighted turbo spin-echo sequence that included only the prostate was also obtained using the
same slice positions as in the axial T2-weighted sequence to check for postbiopsy hemorrhage. The
technical parameters of the MRI pulse sequences
are listed in Table 1.
MR images were interpreted on a PACS workstation (Image Devices PACS, Image Devices).
MR images were considered to be of diagnostic
quality when the prostate and the pelvis were adequately depicted and the images did not show
pronounced artifacts from motion or from a hip
prosthesis or other metal devices placed at surgery. Three independent radiologists (reviewers 1,
2, and 3) who knew that all the patients had prostate cancer but were unaware of the other patient
data interpreted the MR images of all the patients.
All three observers are board-certified radiology
attending physicians with fellowship training in
abdominal imaging and interpretation experience
in MR images of the prostate that had been acquired at different institutions and that exceeded
800 cases (reviewer 1), 400 cases (reviewer 2),
and 600 cases (reviewer 3).
Based on anatomic landmarks on axial T2weighted MR images, the prostate was divided
into six sextants (left and right apex, middle gland,
and base) that provided the framework for interpretation and reporting of MRI findings [16]. According to previous work [3], the base of the prostate extended from the bladder floor and seminal
vesicle–ejaculatory duct junctions to the level craniad to the axial MR image section with the largest
transverse diameter of the prostate. The middle
gland extended from the level of the largest transverse diameter of the prostate to the caudal (inferior) level of the verumontanum. The apex extended from the next caudal level to the urogenital
diaphragm (Fig. 1). Each of the radiologists independently determined the respective slice positions in the axial T2-weighted images of the first
levels of the middle gland and the apex using magnified views on the PACS workstation before evaluating the respective prostatic sextants for the
presence of prostate cancer.
According to previously published work [16],
prostate cancer was identified as a circumscribed
area of decreased signal intensity that had a mass
effect within the peripheral zone of the prostate
but did not have a wedge shape [4, 8, 9, 17, 18].
The likelihood of the presence of prostate cancer
was assessed by the three radiologists independently for each sextant. Likelihood ratings were
derived from a 5-point confidence scale (definitely no prostate cancer, 1; probably no prostate
cancer, 2; indeterminate, 3; probably prostate cancer, 4; definitely prostate cancer, 5). The level of
confidence in detecting prostate cancer was based
on the clarity of the signal decrease within lesions
on T2-weighted images and on the shape and size
of the lesion. A more rounded, bulky lesion of low
signal intensity was associated with a higher likelihood of cancer, whereas a more triangular,
streaky lesion of medium to low signal intensity
was associated with other disease processes, such
as prostatitis or postbiopsy hemorrhage [9, 10,
13, 14, 17, 19]. Axial T1-weighted images of the
prostate were used for assessment of the presence
or absence of postbiopsy hemorrhage. Findings
were recorded using an Excel sheet (Microsoft
Excel 2003). The Excel sheet had been programmed by one of the authors to automatically
generate a Wilcoxon’s-based receiver operating
characteristic (ROC) template as described by
Hanley and McNeil [20].
Data from the Excel sheet were used for calculation of prostate cancer staging accuracy dichotomizing the data from the 5-point scale. Sensitivity, specificity, and overall staging accuracy were calculated.
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Graser et al.
A
B
C
D
E
F
Fig. 1—MR images (A–C) and drawings (D–F) show division of prostate into sextants. Drawings were modified from [16].
A–C, Axial T2-weighted fast spin-echo images show division of prostate of 61-year-old man into sextants: right and left bases (A), middle gland (B), and apex (C).
D, Drawing shows base resembles shape of clover leaf and extends from bladder floor to level cranial to axial MR image section with largest transverse diameter of prostate.
E, Drawing shows middle gland resembles shape of ellipse and extends from level of largest transverse diameter of prostate to caudal (inferior) level of verumontanum.
F, Drawing shows apex resembles shape of trapezoid and extends from next caudal level to urogenital diaphragm.
Pathology Review and Corroboration
of MRI Findings
After radical prostatectomy, each prostate was
coated in ink and fixed in 10% buffered formaldehyde. Each prostatectomy specimen was then attached to a gauze bandage simulating its position
anterior to the rectum in an attempt to preserve the
natural shape of the organ. After transfer of each
specimen to the pathologist’s office, transverse step
sections were obtained at 3- to 4-mm intervals in a
plane perpendicular to the long axis (base to apex)
of the prostate parallel to the MRI plane. Sections
were stained with H and E.
For exact correlation of histopathology findings
with MRI findings, whole-mount step sections
were digitized using a commercially available flatbed scanner (ScanExpress 1200, Mustek). All prostate cancer foci were outlined in green, areas of
ECE were marked in red, and the urethra was
marked in yellow by one pathologist with long-
86
standing experience and a special interest in pathology of the male reproductive system.
Whole-mount step sections were then displayed
on a notebook computer next to the PACS monitor
for evaluation. MRI slices were displayed on our
institution’s PACS at the largest image display setting provided by the PACS workstation. Axial and
coronal T2-weighted images were displayed side
by side on the dual monitor system of the PACS.
Correlation of MRI and histopathology slices was
based on visual assessment of the size and shape of
the respective slice and anatomic landmarks (verumontanum, apex, base).
Correlation of histopathology results and MRI results was based on the sextant framework. Histopathology findings located in the apex and distal periurethral tissues were correlated with the apex at
MRI, as defined earlier. Histopathology findings
identified at the lateral and posterior middle were
correlated with the middle gland at MRI. Histopa-
thology findings seen at the prostatic base, proximal
periurethral tissues, and bladder neck were correlated with the prostatic base at MRI. Histopathology
findings seen anteriorly in the prostatic base and
middle were assumed to extend into the transitional
or central zone unless they were clearly marked as
being confined to the peripheral zone.
A mean prostate cancer Gleason score was recorded for all tumors.
Statistical Analysis
Interobserver reproducibility of respective firstlevel positions of the middle gland and the apex was
determined for reviewers 1 and 2, reviewers 2 and
3, and reviewers 1 and 3. Differences were stated as
deviation between the three observers.
The accuracy of the MRI interpretations compared
with the pathology results was evaluated with ROC
analysis based on data from the 5-point confidence
scale according to methods previously published [20].
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Per-Sextant Localization and Staging of Prostate Cancer
TABLE 2: Reproducibility Among the Three Reviewer Radiologists of Slice Positions
of the First Level of the Prostatic Middle and the First Level of the Apex
No. (%) of Cases
0 Slice
Deviations
± 1 Slice
Deviation
> 1 Slice
Deviation
No. of
Cases
1 vs 2
81 (76.4)
22 (20.8)
3 (2.8)
106
2 vs 3
87 (82.1)
18 (17.0)
1 (0.9)
106
1 vs 3
83 (78.3)
20 (18.9)
3 (2.8)
106
1 vs 2
91 (85.8)
10 (9.4)
5 (4.7)
106
2 vs 3
93 (87.7)
11 (10.4)
2 (1.9)
106
1 vs 3
89 (84.0)
12 (11.3)
5 (4.7)
106
Reviewer
Middle gland position (first slice)
Apex position (first slice)
Note—Data shown in parentheses are percentages.
A
B
Fig. 2—61-year-old man with bilateral organ-confined prostate cancer (stage T2c).
A and B, MR image (A) and whole-mount histopathology image (B) show large tumor focus in left peripheral zone
(straight arrow) and smaller foci in right peripheral zone (curved arrow).
Agreement between interpretations was determined using the kappa statistic, based on dichotomization of the data (score of 1–3, no prostate cancer; score of 4 or 5, prostate cancer). A kappa score
of 0–0.19 was considered poor agreement;
0.20–0.39, fair; 0.40–0.59, moderate; 0.60–0.79,
substantial; and 0.80–1.00, excellent agreement.
The sensitivity and specificity and positive and
negative predictive values were each calculated for
prostate cancer per-sextant localization and for detection of ECE using the dichotomized data from
the ROC analysis.
Results
All MRI examinations were diagnostic. Reproducibility among the three reviewer radiologists of slice positions of the first level of the
prostatic middle and the first level of the apex,
respectively (Fig. 1), is shown in Table 2. In
AJR:188, January 2007
more than 95% of correlated MRI interpretations, slice positions of the sextant framework
were reproduced within ± 1 slice level.
Prostate cancer was present in 417 (65.6%)
and absent from 219 (34.4%) of the 636 sextants at histopathology (Fig. 2). In all cases,
prostate cancer was located within or extended
macroscopically into the peripheral zone of the
prostate at whole-mount histopathology. None
of the patients had a tumor that was confined to
the central gland only. The median prostate
cancer Gleason score was 6 (range, 4–9).
ECE was present in 135 (21.2%) and absent from 501 (78.8%) of the 636 sextants at
histopathology (Fig. 3). Forty-one patients
had ECE (stage T3), and 65 patients had organ-confined disease (stage T2). ECE was
found in one sextant in three patients, in two
sextants in five patients (10 total sextants), in
three sextants in 29 patients (87 total sextants), in four sextants in six patients (24 total
sextants), and in five and six sextants in one
patient, respectively.
The per-patient sensitivity for the recognition of stage T3 was 91.0% for reviewer 1,
84.5% for reviewer 2, and 88.2% for reviewer
3. Specificities were 78.2% for reviewer 1,
83.2% for reviewer 2, and 80.5% for reviewer
3. This accounts for an overall staging accuracy of 92.4% for reviewer 1, 85.9% for reviewer 2, and 83.0% for reviewer 3.
The sensitivity, specificity, and results of
ROC analysis with 95% CIs for localization
of prostate cancer on a per-sextant basis by
means of MRI are listed in Table 3. For ECE
detection, results are listed in Table 4. For
prostate cancer localization and ECE detection, there were no statistically significant differences between ROC areas under the curve
for all three observers.
Agreements between interpretations on a
per-sextant basis among the three independent
radiologists
were
significantly
lower
(p < 0.001) for prostate cancer localization (reviewer 1 vs 2: 499/636 sextants, overall agreement of 78.5%, κ = 0.57; reviewer 2 vs reviewer
3: 488/636 sextants, overall agreement of
76.7%, κ = 0.55; reviewer 1 vs reviewer 3:
475/636 sextants, overall agreement of 74.7%, κ
= 0.53) than for ECE localization (reviewer 1 vs
reviewer 2: 568/636 sextants, overall agreement
of 89.3%, κ = 0.77; reviewer 2 vs reviewer 3:
543/636 sextants, overall agreement of 85.4%, κ
= 0.75; reviewer 1 vs reviewer 3: 552/636 sextants, overall agreement of 86.8%, κ = 0.78).
These values are consistent with moderate
agreement for prostate cancer localization and
substantial agreement for ECE localization.
Discussion
It has been shown previously that prostate
cancer has a heterogeneous, multifocal, and
multizonal nature [21]. Prostate cancer treatment depends on local tumor stage, Gleason
score, and the presence or absence of distant
metastases at the time of diagnosis. In our
study population, tumors showed Gleason
scores ranging from 4 to 9, with most patients
being diagnosed with a Gleason score of 6 at
histopathology. Local tumor extent is an independent prognostic factor in local recurrence
in prostate cancer patients [22]. To select patients for curative surgical resection of prostate cancer, preoperative assessment by
means of clinical staging and MRI is of great
importance. MRI is clearly the most exact imaging technique in local staging of prostate
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Graser et al.
cancer [23], especially when state-of-the-art
high-field scanners and a combination of endorectal and pelvic phased-array surface coils
are used [10]. It is superior to endorectal
sonography in its ability to detect seminal
vesicle invasion and early extraprostatic tumor spread across the capsule [24].
Although local tumor extent influences
prognosis in patients with prostate cancer, until now most studies have investigated MRI
staging accuracy rather then its ability to localize single tumor foci. Therefore, we undertook our study to correlate MRI findings with
whole-mount step section histopathology.
The whole-mount approach enables exact localization and size assessment of single tumor
foci. At step section histopathology, studies
based on whole mounts found higher incidences of stage T3 tumors than studies using
a standard workup of suspicious areas only
[25, 26]. Considering the prognostic importance of local tumor stage, working up prostatectomy specimens is warranted. Based on
the shape of single whole-mount sections,
correlation of MRI and histopathology findings was performed.
Dividing the prostate into sextants (right and
left bases, middle gland, and apex) on the basis
of morphologic and anatomic criteria [2, 3] provides a framework for localization of intraprostatic findings that follows closely the way in
which urologists perform biopsies and report
their findings. In this study, we sought to show
that the prostatic base, mid gland, and apex can
be reliably identified by different observers at
MRI. Among the three observers, results differed by no more than one MRI slice in more
than 95% of patients. Because anatomic landmarks that have to be identified for correct division of the prostate into sextants are well visualized and can be readily identified on endorectal
coil MR images of the prostate, this pattern can
be used in reporting MRI of the prostate in the
clinical routine [16]. Although it has been argued that findings of lesions suspicious for prostate cancer on MR images should be reported on
a per-nodule basis rather than on a per-sextant
basis [27], there is as yet no evidence to suggest
that findings of individual nodules are more easily reproduced than findings of signs indicating
prostate cancer in an individual sextant of the
prostate. Also, it has not been established that
reporting on a per-nodule basis without the use
of a framework for orientation would improve
sensitivity, specificity, or clinical utility of MRI
of the prostate [27].
Based on a standard protocol for MRI of
the prostate, image interpretation for the pres-
88
ence or absence of prostate cancer essentially
relies on axial and coronal T2-weighted images [11, 13]. In T2-weighted images, healthy
prostate tissue in the peripheral zone shows a
bright homogeneous signal that is set off
against the low-signal rim of the prostatic
capsule on the outside. On the inside, healthy
prostate tissue contrasts with the mixed low to
medium signal of the prostatic pseudocapsule, central zone, and transitional zone [10,
13]. Prostate cancer occurs in the peripheral
zone in 70–80% of cases [11, 14, 28] and is
frequently recognized by its low signal intensity [11]. However, foci of prostate cancer are
easily missed when they measure less than 4
mm2 [29], and other disease entities may
mimic prostate cancer when they have low
signal intensity on T2-weighted MR images
[30]. Such entities include foci of chronic or
granulomatous prostatitis, nodules of benign
prostatic hyperplasia in the peripheral zone
[13, 30], or areas of hemorrhage or scarring
secondary to prostate biopsy [11, 13, 14].
In a study that localized prostate cancer to a
sextant of the peripheral zone on the basis of
combined MRI and MR spectroscopy, Scheidler
et al. [2] found that interobserver agreement on
MRI findings was moderate, with a kappa value
of 0.43. In our study, we found kappa values of
0.49–0.60 for prostate cancer localization, indicating moderate to substantial interobserver
agreement. Higher values were achieved for localization of ECE (κ = 0.59–0.67). Overall agreement on per-sextant localization of prostate cancer was significantly lower than on localization of
ECE. The three observers reached comparable
overall staging accuracies based on ROC data.
Analysis of sextants showed that single
sextants containing prostate cancer at histopathology were missed by all three observers. Review of these sextants showed only
slight, if any, signal abnormalities and lack
of characteristic prostate cancer imaging
features such as a low-signal-intensity mass.
Relatively low kappa scores show that there
is substantial inconsistency among observers in the individual perception and interpretation of signal abnormalities in the prostatic
peripheral zone associated with the presence
of prostate cancer. Our study results indicate
that some prostate cancer foci were missed
by all three observers. In addition, we found
interpretation errors concerning sextants
where all observers detected an abnormality
but interpreted the findings differently. In
general, observers used values 2–4 (with 2
meaning probably no prostate cancer; 3, indeterminate; and 4, probably prostate can-
cer) from the 5-point confidence scale more
often in these sextants, leading to interobserver disagreement. This underlines that
previously published signs of prostate cancer [9, 10, 13] leave too much room for individual interpretation.
Similarly, single sextants containing ECE
were missed by all observers. Review of these
sextants showed that they contained only
minimal ECE of 1 mm or less on histopathology. Our results underline that if only small
clusters of tumor cells are seen outside the
prostatic capsule at histopathology, they cannot be visualized on MRI using current techniques. Probably, the hypointense signal routinely encountered in the neurovascular
bundle region renders detection of tumor
spread more difficult.
The pathologist marked extracapsular tumor spread on the whole-mount sections using
red. Because the digitized whole-mount specimens were displayed next to the MR images,
the possibility of misinterpretation of the pathologist’s written report was excluded in our
study. In addition, working up all prostatectomy specimens in a whole-mount fashion reduces sampling error to a minimum because
the entire prostate is sectioned and analyzed.
Because we sought to correlate findings by
sextant, our pathologist carefully outlined each
prostate cancer focus on the specimens. Reviewing the digitalized whole-mount specimens of all 106 patients showed that all but
eight patients had multifocal prostate cancer.
In a substantial number of cases, very small
separate foci of prostate cancer were identified
that were not connected to large tumor foci.
This suggests that in previous studies that did
not use whole mounts for correlation, small tumor foci may have been missed. In addition, in
21 patients tumor foci within the central and
transitional zones were identified. In 18 of
these 21 cases, extension of tumor into the central gland could be visualized retrospectively.
Due to the mixed T2 signal intensity of hyperplastic transitional zone tissue, tumor foci cannot be reliably identified prospectively. The
use of MRI in combination with MR spectroscopy and contrast-enhanced perfusion imaging
seems a promising method by which to overcome this limitation [31].
Comparing MRI findings with wholemount prostatectomy specimens allows exact
correlation of findings. In our study, we
sought to eliminate every possible confounding factor that may lead to misinterpretation
of pathology findings. We directly compared
single MRI slices with respective whole-
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Per-Sextant Localization and Staging of Prostate Cancer
A
B
Fig. 3—Stage T3a prostate cancer with extracapsular extension at left base in 61-year-old man.
A and B, Axial T2-weighted MR image (A) and whole-mount histopathology image (B) show there is thickening and
bulging of prostatic capsule at left base and low-signal-intensity material in neurovascular bundle region (straight
arrow). Smaller tumor foci are seen in right peripheral zone (curved arrow).
TABLE 3: Receiver Operating Characteristic (ROC)–Based Analysis of
Interpretations of MRI Examinations of the Prostate for Presence of
Prostate Cancer on a Per-Sextant Basis (Right and Left Bases, Middle
Gland, and Apex)
% (No. of Sextants with Positive Findings /
Total No. of Sextants)
Reviewer
Sensitivity
Specificity
Az
95% CI
1
82.3 (343/417)
70.3 (154/219)
0.802
0.757–0.848
2
78.7 (328/417)
65.6 (144/219)
0.776
0.727–0.826
3
71.2 (297/417)
79.5 (174/219)
0.732
0.665–0.773
Note—Az = area under the ROC curve.
TABLE 4: Receiver Operating Characteristic (ROC)–Based Analysis of
Interpretations of MRI Examinations of the Prostate for Presence of
Extracapsular Extension on a Per-Sextant Basis (Right and Left Bases,
Middle Gland, and Apex)
% (No. of Sextants with Positive Findings /
Total No. of Sextants)
Reviewer
Sensitivity
Specificity
Az
95% CI
1
71.1 (96/135)
89.8 (450/501)
0.793
0.728–0.857
2
81.5 (110/135)
80.2 (402/501)
0.761
0.693–0.828
3
78.5 (106/135)
81.4 (408/501)
0.755
0.685–0.802
Note—Az = area under the ROC curve.
mount specimen slices on two adjacent monitors. This direct comparison yielded interesting results: On the one hand, there were easy
cases with MR signal abnormalities corresponding exactly to histopathologically
proven foci of prostate cancer. On the other
hand, there were difficult cases that showed
AJR:188, January 2007
very subtle and noncharacteristic imaging
findings; in these latter cases, observer disagreement was observed more frequently.
Our results of 83–93% overall staging accuracy agree with those published in the literature. The use of the sextant framework allows a reproducible way of reporting MRI
findings in prostate imaging. Being forced to
exactly localize tumor foci may lead to improved staging accuracy. We found that revealing histopathology findings to the radiologists participating in this study was a very
educational experience and may have induced
a learning curve.
The use of MRI in prostate cancer staging
is warranted only if the results of this examination influence patient management in a
substantial number of patients. Certainly, performing MRI with an endorectal coil is the
most exact imaging technique to date. It
should be used in patients with clinically localized prostate cancer only to allow reproducibly good results.
Several studies have emphasized the importance of observer experience in MRI of the
prostate. A multicenter study examining the
interpretation performance of nine different
observers in MRI of the prostate reported accuracies between 69% and 79% [12]. In our
study, we did not find significant differences
among the three observers, which was probably due to their similar levels of experience.
Our study has several limitations. First, observers were aware of the presence of prostate
cancer in all cases; therefore, differentiation of
prostate cancer foci and inflammatory changes
of the peripheral zone may have been influenced. All other clinical information, including
serum PSA values, was withheld. Prostate cancer staging is one of the major indications for
prostatic MRI, and our setting therefore resembles the clinical routine. In some of the cases,
overcalling of subtle signal abnormalities may
have occurred because observers knew about
the presence of prostate cancer.
Another limitation represents the lack of
MR spectroscopy, which was not performed
in our institution at the time this study was
conducted. It has been well documented that
MR spectroscopy increases sensitivity and
specificity in prostate cancer localization and
in the localization of ECE [27, 32, 33]. The
widespread use of MRI without spectroscopy,
however, still represents routine clinical practice in preoperative prostate cancer staging in
many centers.
In our study, all three observers had extensive experience in interpreting MRI of the
prostate. However, it has already been shown
that radiologists without genitourinary imaging training perform poorly compared with
genitourinary radiologists in interpreting
MRI of the prostate [12]. Although observer
experience differed slightly among the single
observers of our study, each of the three ob-
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084.fm — 12/1/06
Graser et al.
servers seemed to have a specific pattern of
recognizing and calling abnormalities and reporting imaging findings in MRI of the prostate. Although one of the observers tended to
overcall prostate cancer presence in respective prostatic sextants, the other two observers
were more specific, reporting fewer falsepositive findings.
In conclusion, MRI of the prostate with
combined endorectal–pelvic phased-array coils
represents the state-of-the-art imaging technique for local tumor staging in patients with
biopsy-proven prostate cancer. Application of
the sextant framework to MRI of the prostate
provides a highly reliable aid in the reporting
and communication of MRI findings.
Our study underlines that preoperative local
staging of prostate cancer relies on state-ofthe-art MRI performed by expert observers.
References
1. Quinn M, Babb P. Patterns and trends in prostate
cancer incidence, survival, prevalence and mortality. Part I. International comparisons. BJU Int 2002;
90:162–173
2. Scheidler J, Hricak H, Vigneron DB, et al. Prostate
cancer: localization with three-dimensional proton
MR spectroscopic imaging—clinicopathologic
study. Radiology 1999; 213:473–480
3. Mueller-Lisse UG, Vigneron DB, Hricak H, et al.
Localized prostate cancer: effect of hormone deprivation therapy measured by using combined threedimensional 1H MR spectroscopy and MR imaging—clinicopathologic case-controlled study. Radiology 2001; 221:380–390
4. Wefer AE, Hricak H, Vigneron DB, et al. Sextant localization of prostate cancer: comparison of sextant
biopsy, magnetic resonance imaging and magnetic
resonance spectroscopic imaging with step section
histology. J Urol 2000; 164:400–404
5. Chan TW, Kressel HY. Prostate and seminal vesicles after irradiation: MR appearance. J Magn
Reson Imaging 1991; 1:503–511
6. Chen M, Hricak H, Kalbhen CL, et al. Hormonal ablation of prostatic cancer: effects on prostate morphology, tumor detection, and staging by endorectal
coil MR imaging. AJR 1996; 166:1157–1163
7. Kalbhen CL, Hricak H, Shinohara K, et al. Prostate
carcinoma: MR imaging findings after cryosurgery.
Radiology 1996; 198:807–811
8. Yu KK, Scheidler J, Hricak H, et al. Prostate cancer:
prediction of extracapsular extension with endorectal
MR imaging and three-dimensional proton MR spectroscopic imaging. Radiology 1999; 213:481–488
9. Cruz M, Tsuda K, Narumi Y, et al. Characterization
of low-intensity lesions in the peripheral zone of
prostate on pre-biopsy endorectal coil MR imaging.
Eur Radiol 2002; 12:357–365
10. Hricak H, White S, Vigneron D, et al. Carcinoma of
the prostate gland: MR imaging with pelvic phasedarray coils versus integrated endorectal–pelvic
phased-array coils. Radiology 1994; 193:703–709
11. Engelbrecht MR, Jager GJ, Laheij RJ, Verbeek AL,
van Lier HJ, Barentsz JO. Local staging of prostate
cancer using magnetic resonance imaging: a metaanalysis. Eur Radiol 2002; 12:2294–2302
12. Mullerad M, Hricak H, Wang L, Chen HN, Kattan
MW, Scardino PT. Prostate cancer: detection of extracapsular extension by genitourinary and general
body radiologists at MR imaging. Radiology 2004;
232:140–146
13. Heuck A, Scheidler J, Sommer B, Graser A, MullerLisse UG, Massmann J. MR imaging of prostate
cancer [in German]. Radiologe 2003; 43:464–473
14. White S, Hricak H, Forstner R, et al. Prostate cancer: effect of postbiopsy hemorrhage on interpretation of MR images. Radiology 1995; 195:385–390
15. Beyersdorff D, Taupitz M, Winkelmann B, et al. Patients with a history of elevated prostate-specific antigen levels and negative transrectal US-guided
quadrant or sextant biopsy results: value of MR imaging. Radiology 2002; 224:701–706
16. Mueller-Lisse U, Mueller-Lisse U, Scheidler J,
Klein G, Reiser M. Reproducibility of image interpretation in MRI of the prostate: application of the
sextant framework by two different radiologists.
Eur Radiol 2005; 15:1826–1833
17. Langlotz C, Schnall M, Pollack H. Staging of prostatic cancer: accuracy of MR imaging. Radiology
1995; 194:645–646
18. Bartolozzi C, Menchi I, Lencioni R, et al. Local
staging of prostate carcinoma with endorectal coil
MRI: correlation with whole-mount radical prostatectomy specimens. Eur Radiol 1996; 6:339–345
19. Lovett K, Rifkin MD, McCue PA, Choi H. MR imaging characteristics of noncancerous lesions of the
prostate. J Magn Reson Imaging 1992; 2:35–39
20. Hanley JA, McNeil BJ. The meaning and use of the
area under a receiver operating characteristic (ROC)
curve. Radiology 1982; 143:29–36
21. Chen ME, Johnston DA, Tang K, Babaian RJ, Troncoso P. Detailed mapping of prostate carcinoma
foci: biopsy strategy implications. Cancer 2000;
89:1800–1809
22. Kikuchi E, Scardino PT, Wheeler TM, Slawin KM,
Ohori M. Is tumor volume an independent prognostic factor in clinically localized prostate cancer? J
Urol 2004; 172:508–511
23. Coakley FV, Qayyum A, Kurhanewicz J. Magnetic
resonance imaging and spectroscopic imaging of
prostate cancer. J Urol 2003; 170(6 Pt 2):S69–S75
24. Presti JC Jr, Hricak H, Narayan PA, Shinohara K,
White S, Carroll PR. Local staging of prostatic carcinoma: comparison of transrectal sonography and
endorectal MR imaging. AJR 1996; 166:103–108
25. Donahue RE, Miller GJ. Adenocarcinoma of the
prostate: biopsy to whole mount—Denver VA experience. Urol Clin North Am 1991; 18:449–452
26. Middleton RG, Smith JA Jr, Melzer RB, Hamilton
PE. Patient survival and local recurrence rate following radical prostatectomy for prostatic carcinoma. J Urol 1986; 136:422–424
27. Dhingsa R, Qayyum A, Coakley FV, et al. Prostate
cancer localization with endorectal MR imaging and
MR spectroscopic imaging: effect of clinical data on
reader accuracy. Radiology 2004; 230:215–220
28. Massmann J, Funk A, Altwein J, Praetorius M.
Prostate carcinoma (PC): an organ-related specific
pathological neoplasm [in German]. Radiologe
2003; 43:423–431
29. Schiebler ML, Schnall MD, Pollack HM, et al. Current
role of MR imaging in the staging of adenocarcinoma
of the prostate. Radiology 1993; 189:339–352
30. Kahn T, Burrig K, Schmitz-Drager B, Lewin JS,
Furst G, Modder U. Prostatic carcinoma and benign
prostatic hyperplasia: MR imaging with histopathologic correlation. Radiology 1989; 173:847–851
31. Yuen JS, Thng CH, Tan PH, et al. Endorectal magnetic resonance imaging and spectroscopy for the
detection of tumor foci in men with prior negative
transrectal ultrasound prostate biopsy. J Urol 2004;
171:1482–1486
32. Kaji Y, Kurhanewicz J, Hricak H, et al. Localizing
prostate cancer in the presence of postbiopsy
changes on MR images: role of proton MR spectroscopic imaging. Radiology 1998; 206:785–790
33. Rajesh A, Coakley FV. MR imaging and MR spectroscopic imaging of prostate cancer. Magn Reson
Imaging Clin N Am 2004; 12:557–579, vii
F O R YO U R I N F O R M AT I O N
The reader’s attention is directed to the article by Reinsberg et al., “Combined
Use of Diffusion-Weighted MRI and 1 H MR Spectroscopy to Increase Accuracy in
Prostate Cancer Detection,” which appears on page 91 of this issue.
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