Open Journal of Urology, 2012, 2, 198-205
http://dx.doi.org/10.4236/oju.2012.223035 Published Online October 2012 (http://www.SciRP.org/journal/oju)
Endorectal Magnetic Resonance Imaging and Spectroscopy
Are Useful for Selecting Candidates for Biopsy among
Patients with Persistently Elevated Prostate
Specific Antigen
Josep Comet-Batlle1*, Carles Barceló-Vidal2, Joan Carles Vilanova-Busquets3,
Roger Boix-Orri1, Albert Maroto-Genover4, Joan Areal-Calama5,
Margarita Osorio-Fernandez4, Ferran Perez-Bueno6, Nuria Fuertes-Izquierdo1
1Urology Department, Hospital Dr. Josep Trueta, Catalonia, Spain
2Department of Computer Science and Applied Mathematics, University of Girona, Catalonia, Spain
3Ressonància Girona, Catalonia, Spain
4Radiology Department, Hospital Dr. Josep Trueta, Catalonia, Spain
5Urology Department, Hospital Trias Pujol, Catalonia, Spain
6Pathology Department, Hospital Dr. Josep Trueta, Catalonia, Spain
Received August 3, 2012; revised September 4, 2012; accepted September 19, 2012
ABSTRACT
Objective: To evaluate the efficacy of endorectal Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spet-
roscopic Imaging (MRSI) combined with total prostate-specific antigen (tPSA) and free prostate-specific antigen (fPSA)
in selecting candidates for biopsy. Subjects and Methods: 246 patients with elevated tPSA (median: 7.81 ng/ml) un-
derwent endorectal MRI and MRSI before Transrectal Ultrasound (TRUS) biopsy (10 peripheral + 2 central cores);
patients with positive biopsies were treated with radical intention; those with negative biopsies were followed up and
underwent MRSI before each additional biopsy if tPSA rose persistently. Mean follow-up: 27.6 months. We compared
MRI, MRSI, tPSA, and fPSA with histopathology by sextant and determined the association between the Gleason score
and MRI and MRSI. We determined the most accurate combination to detect prostate cancer (PCa) using receiver oper-
ating curves; we estimated the odds ratios (OR) and calculated sensitivity, specificity, and positive and negative predic-
tive values. Results: No difference in tPSA was found between patients with and without PCa (p = 0.551). In the pe-
ripheral zone, the risk of PCa increased with MRSI grade; patients with high-grade MRSI had the greatest risk of PCa
over time (OR = 328.6); the model including MRI, MRSI, tPSA, and fPSA was more accurate (Area under Curve: AUC
= 95.7%) than MRI alone (AUC = 85.1%) or fPSA alone (AUC = 78.1%), but not than MRSI alone (94.5%). In the
transitional zone, the model was less accurate (AUC = 84.4%). The association (p = 0.005) between MRSI and Gleason
score was significant in both zones. Co nclusions: MRSI is useful in patients with elevated tPSA. High-grade MRSI
lesions call for repeated biopsies. Men with negative MRSI may forgo further biopsies because a significantly high
Gleason lesion is very unlikely.
Keywords: Endorectal MRI; Spectroscopy; Prostate Cancer; Diagnosis; Prostate Specific Antigen (PSA); Free to Total
PSA Ratio (F/T PSA)
1. Introduction
The two most common methods of screening for prostate
cancer (PCa), digital rectal examination (DRE) and se-
rum total prostate-specific antigen (tPSA) levels, yield
suboptimal accuracy. The specificity of tPSA is poor for
levels < 10 ng/ml [1,2]. Thus, 60% to 75% of men with
tPSA between 4 ng/ml and 10 ng/ml undergo unneces-
sary biopsies [3]. Moreover, men can have elevated tPSA
and multiple previous negative biopsies before a diagno-
sis of PCa is established. The use of %fPSA reduces the
number of unnecessary biopsies whilst maintaining a
high PCa detection rate [4,5]. Combined endorectal MRI
and 3D-MRSI have proven accurate in determining the
location of PCa [6,7]. We aimed to assess the value of
endorectal MRI and 3D-MRSI combined with %fPSA to
select patients for biopsy among men with elevated tPSA
throughout long-term follow-up.
*Corresponding author.
C
opyright © 2012 SciRes. OJU

J. COMET-BATLLE ET AL. 199
2. Material and Methods
2.1. Subjects
Our institutional review board approved this prospective
study, and all patients provided informed consent.
We selected 246 patients (median age, 61.0 y; range,
44 - 77) to undergo endorectal MRI/3D-MRSI before 12-
core transrectal ultrasound-guided (TRUS) biopsy. Inclu-
sion criteria were rise in tPSA > 50% or tPSA velocity >
0.75 ng/ml/year and negative or inconclusive DRE. No
patients with clear nodules or hardness of the prostate at
DRE were included. Before entering the study, 3 pa-
tients had undergone retropubic adenomectomy and 18
transurethral resection of the prostate (TURP) for symp-
toms of benign prostatic hyperplasia (BPH), so the tran-
sition zone was not biopsied in these 21 patients because
of a lack of visible tissue at TRUS.
Patients with negative biopsies were followed-up, and
they underwent MRI/3D-MRSI before each additional
biopsy (up to 3) if tPSA rose persistently. Patients who
were found prostate cancer were treated with radical
treatment (Radical prostatectomy or Radiotherapy) if
indicated. Variables collected included tPSA level and
%fPSA.
2.2. MRI and 3D-MRSI Techniques
We used a 1.5-T whole-body MRI unit (Signa Horizon
V.12.0; GE) with a body coil and a phased-array pelvic
coil together with an expandable endorectal coil (Endo
ATD Medrad; Warrendale, PA, USA) for signal recap-
tion. We acquired A) axial T1-weighted sequences of the
pelvic region and B) axial and coronal high resolution
T2-weighted fast spin-echo sequences of the prostate and
seminal vesicles. The 3D-MRSI data were processed and
aligned with the corresponding MR image on a work-
station using commercially available software (Functool,
GE). Peak areas for choline, creatine, and citrate were
calculated using numeric integration. Metabolic ratio
maps of [choline + creatine]/citrate ([CC]/Ci) were gen-
erated.
The 3D-MRSI datasets were acquired as 16 × 8 × 8
phase-encoded spectral arrays (1024 voxels) with a spa-
tial resolution of 0.24 - 0.34 cm³ and 1000130 . Image
acquisition took 19 minutes and the entire examination,
including coil placement, patient positioning, and MRI
and 3D-MRSI acquisition took 50 to 60 minutes.
2.3. Image Interpretation
Three radiologists with extensive experience in MRI and
3D-MRSI imaging interpretation (12, 6 and 4 years ex-
perience, respectively) evaluated in consensus all MRI
and MR spectroscopic findings. For tumor localization,
the prostate was split along the midline and further di-
vided into the apex, middle, and base of the gland (Fig-
ure 1). Thus, the prostate was divided into 6 regions in
the peripheral zone (PZ) and 2 in the transition zone (TZ).
Image evaluation consisted of two parts. First, the three
readers scored the T2-weighted images using a five-point
scale. The presence of cancer, identified as an area of
low signal intensity, was recorded for each region. Read-
ers graded their confidence that cancer was present in
each region on a five-point scale, as follows: grade 1
indicated definitely no tumor; 2, probably no tumor; 3,
tumor possible; 4, tumor probable; and 5, tumor defini-
tely present. Second, all 3D-MRSI data were read inde-
pendently. All the voxels in the 8 regions were evaluated
and each region was also scored on the five-point scale.
Mean values of the [CC]/Ci ratio were categorized using
different scores for the PZ and TZ, according to Kurha-
newicz et al. [8]. In the PZ, a score of 1 was assigned to
voxels with [CC]/Ci<0.5; 2 to voxels with 0.5  [CC]/Ci
< 0.6; 3 to voxels with 0.6  [CC]/Ci < 0.7; 4 to voxels
with 0.7  [CC]/Ci < 0.8; and 5 to voxels with [CC]/Ci 
0.8. For the TZ, score 1 was assigned to voxels with a
[CC]/Ci<0.8; 2 to voxels with 0.8  [CC]/Ci < 0.9; 3 to
voxels with 0.9  [CC]/Ci < 1.0; 4 to voxels with 1.0 
[CC]/Ci < 1.1; and 5 to voxels with [CC]/Ci  1.1.
2.4. Biopsy
After standard preparation, all patients underwent TRUS
biopsy by using a US scanner (Allegra; Siemens, Erlan-
gen, Germany) with a 6.5 MHz sector probe. Twelve
prostatic cores were obtained using an 18-gauge biopsy
needle (Bard Urological; Covington, GA, USA) with a
spring-loaded biopsy gun (Manan Medical Pruducts,
Northbrook, Ill.). In patients without pathological images
on MRI/3D-MRSI, 10 cores were obtained from the PZ
Figure 1. Schematic representation of the different areas in
which the prostate was divided (6 in the Peripheral Zone
and 2 in the Transition Zone) and the cores taken from each
area in every biopsy.

J. COMET-BATLLE ET AL. 200
(Sextant biopsy + 4 lateral), and 2 from the TZ (one each
side) (Figure 1). In patients with pathological images on
MRI/3D-MRSI, additional cores were obtained from the
site of the lesion. All cores were labeled according to
their topographic location. The urologists responsible for
carrying out the TRUS biopsy (JCB anb RBO) had ex-
tensive experience before this study.
When the biopsy after MRSI was negative, patients
were followed up; if PSA kept rising and further biopsies
were needed, patients underwent MRI/3D-MRSI before
each biopsy. We performed a maximum of three biopsies
if PCa was not found. 219 patients underwent a single
biopsy after MRI/3D-MRSI, 17 patients underwent 2 bio-
psies, and 10 patients underwent 3 biopsies.
The material for histopathological evaluation consisted
of biopsy cores, adenomectomy or TURP specimens from
treatments performed during the study, and the whole
gland in patients with PCa who underwent radical pro-
statectomy (RP).
2.5. Statistical Analysis
The PZ and TZ were analyzed separately. The maximum
values of all readings for MRI and 3D-MRSI were taken
for analysis in the PZ and in the TZ. We evaluated the
four predictive variables (MRI, 3D-MRSI (5-point ordi-
nal scales), tPSA, and %fPSA (continuous scales)) sepa-
rately by fitting a binary logistic regression model with
these variables as predictors. For MRI and 3D-MRSI, we
considered 3 categories: MRI = 1 - 2 (reference); MRI =
3; and MRI = 4 - 5. Exceptionally, MRI was split into 2
categories [MRI = 1 - 2 (reference) and MRI = 3 - 5] in
the statistical analysis of the TZ because few patients had
MRI ≥ 4.
Two categories were considered for tPSA: ≤ 10 ng/ml
(reference) and >10 ng/ml and two for fPSA: ≥ 15% (ref-
erence) and < 15%, according to Okamura et al. [9].
We estimated the odds ratio (OR) of each category and
its accuracy for predicting PCa from the area under re-
ceiver operating characteristic curves (AUC). Sensitivity,
specificity, positive predictive value (PPV), and negative
predictive value (NPV) were also calculated. The OR of
each category was compared with the OR = 1 of the ref-
erence category. The association between Gleason score
and MRI/3D-MRSI scores was measured by Goodman
and Kruskal’s gamma coefficient (G). Gleason scores
were grouped into three categories: up to Gleason 3 + 3;
from 3 + 4 to 4 + 3; and from 3 + 5 to 5 + 5. We consid-
ered p-values < 0.05 significant.
3. Results
Median tPSA was 7.81 n/ml (range: 0.16 - 71.00), and
median fPSA was 13.08% (range: 0.12% - 41.70%). Me-
dian follow-up was 22.4 months (range: 6 - 81.3 months).
At the end of the study, 16 patients had undergone
TURP or adenomectomy for BPH, 29 radical prostatec-
tomy (RP), 25 radiation therapy (RT), and 5 hormone
therapy (HT). PCa was detected in the PZ (areas 1 to 6)
in 31.7% (78/246) patients and in the TZ (areas 7 - 8) in
15.1% (34/225); 82.3% (28/34) of patients with cancer in
the TZ also had cancer in the PZ.
3.1. Peripheral Zone
Mean tPSA in patients with PCa (9.63 ng/ml) was not
statistically different than in patients without PCa (9.95
ng/ml) (p = 0.551). The estimated AUC of tPSA as a
predictive variable was 0.708 (Table 1(A) and Figure 2).
Mean %fPSA was lower in patients with PCa than in
those without (12.4% vs. 15.0%; p < 0.001). The estimat-
ed AUC of %fPSA was 0.781 (Table 1(A) and Figure 2).
Biopsies were negative in all (29/29) patients with
grade 1 lesions at MRI and in 86.2% (100/116) of those
with grade 2 lesions. Biopsies were positive in all (8/8)
patients with grade 5 lesions at MRI and in 83.3% (10/12)
of those with grade 4 lesions (Table 2(A)). The AUC of
MRI was 0.851 (Figure 2). The OR of MRI = 3 and MRI
= 4 - 5 were 7.9 and 57.4, respectively (Table 1(A)).
In the analysis of 3D-MRSI, 95.1% (156164) of pati-
ents with grade 1-2 lesions had negative biopsies and 95.3%
(41/43) of patients with grade 4-5 3D-MRSI lesions had
positive biopsies during follow-up (Table 2(A)). Never-
theless, one of the two patients with grade 4-53D-MRSI
lesions without cancer in the PZ had a positive biopsy
0.00 0.25 0.50 0.75 1.00
S
ensitivit
y
0.00 0.25 0.50 0.75 1.00
1-Specificity
MSI+MRSI+tPSA+fPSA (AUC=0.958)
MRSI (AUC=0.945)
MRI (AUC=0.851)
fPSA (AUC=0.775)
tPSA (AUC=0.708)
No discrimination line
Figure 2. Prostate peripheral zone. Receiver operating cha-
racteristic (ROC) curves for the predictive variables mag-
netic resonance imaging (MRI), magnetic resonance spec-
troscopy (3D-MRSI), total prostate-specific antigen (tPSA),
free-to-total prostate-specific antigen ratio (fPSA), and the
combination of all four variables. The overall accuracy of
each model is specified in the area under the corresponding
ROC curves (AUC).

J. COMET-BATLLE ET AL. 201
Table 1. Odds ratios (OR), area under the receiver operating characteristic curves (AUC), sensitivity, specificity, positive
predictive value (PPV), and negative predictive value (NPV) for the predictors MRI, 3D-MRSI, tPSA, and fPSA of prostate
cancer in the four individual models and in the multivariate model. Models are adjusted for the number of previous negative
biopsies and age.
(A)
Peripheral zone
Model OR p-valueb AUC p-valuec Sensitivity (%)Specificity (%) PPV (%) NPV (%)
Individual predictors
MRI (5-point scale) 0.851 <0.001 79.5 76.8 61.4 89.0
MRI = 1,2a 1
MRI = 3 7.9 <0.001
MRI = 4,5 57.4 <0.001
MRSI (5-point scale) 0.945 <0.001 89.7 92.9 85.4 95.1
MRSI = 1,2a 1
MRSI = 3 56.6 <0.001
MRSI = 4,5 328.6 <0.001
tPSA 0.708 <0.001 47.4 83.3 56.9 77.3
≤10 ng/mla 1
>10 ng/ml 1.4 0.327
fPSA 0.781 <0.001 64.1 79.8 59.5 82.7
≥15%a 1
<15% 5.6 <0.001
Multivariate model (all preditors) 0.957 91.0 94.6 88.8 95.8
(B)
Transition zone
Model OR p-valueb AUC p-valuec Sensitivity (%)Specificity (%) PPV (%) NPV (%)
Individual predictors
MRI (5-point scale) 0.758 0.061 55.9 82.7 36.5 91.3
MRI = 1,2a 1
MRI = 3,4,5 15.9 <0.001
MRSI (5-point scale) 0.813 0.284 55.9 95.3 67.9 92.4
MRSI = 1,2a 1
MRSI = 3 10.1 <0.001
MRSI = 4,5 56.2 <0.001
tPSA 0.745 0.042 58.8 80.6 35.1 91.7
≤10 ng/mla 1
>10 ng/ml 4.2 0.001
fPSA 0.705 <0.001 64.7 63.9 24.2 91.0
≥15%a 1
< 15% 2.1 0.024
Multivariate model (all preditors) 0.844 76.5 83.2 44.8 95.2
a. Reference category, b. p-values of the OR compared to the reference category for the corresponding predictor, c. p-values of the AUC compared to the multi-
variate model.

J. COMET-BATLLE ET AL. 202
Table 2. Biopsy result versus endorectal MRI and 3D-MRSI grades.
(A)
Peripheral zone
MRI grade MRSI grade
Biopsy result
1 2 3 4 5 1 2 3 4 5 Total
Negative (0) 29 100 37 2 0 16 140 10 1 1 168
Positive (1) 0 16 44 10 8 2 6 29 27 14 78
Total 29 116 81 12 8 18 146 39 28 15 246
(B)
Transitional zone
MRI grade MRSI grade
Biopsy result
1 2 3 4 5 1 2 3 4 5 Total
Negative (0) 14 172 5 0 0 15 167 7 2 0 191
Positive (1) 0 22 9 3 0 0 15 6 11 2 34
Total 14 194 14 3 0 15 182 13 13 2 225
(C)
Gleason grades of PCa versus the grade of lesions detected at MRI/3D-MRSI
MRI grade MRSI grade
Gleason grade No of tumors 1 - 2 3 4 - 5 1 - 23 4 - 5
≤6 (3 + 3) 22 8 11 3 6 7 9
3 + 4 to 4 + 3 33 9 20 4 5 14 14
3 + 5 to 5 + 5 29 3 15 11 2 7 20
Total 84 20 46 18 13 28 43
G = 0.431, p = 0.001, G = 0.367; p = 0.005.
(Gleason 6: 3 + 3) in the right TZ in the second set of
biopsies. The second patient had a history of superficial
bladder cancer treated with BCG 5 years before TRUS
biopsy, which found granulomas suggestive of tubercu-
losis. The AUC of 3D-MRSI was 0.945 (Figure 2). The
OR of 3D-MRSI = 3 and 3D-MRSI = 4 - 5 were 56.6 and
328.6, respectively (Table 1(A)).
On the combined analysis of MRI-3D-MRSI, 100%
(17/17) of patients with MRI = 4 - 5 and 3D-MRSI = 4 -
5 had PCa in the PZ. Four patients with PCa had MRI =
1 - 2 and 3D-MRSI = 1 - 2; they were found PCa in the
third set of biopsies and all had a Gleason 6 (3 + 3) PCa
in a single core at biopsy. The AUC of the model com-
bining all variables (MRI, 3D-MRSI, tPSA, and fPSA)
was 0.957 (Figure 2), which is significantly greater than
the AUC of MRI alone, tPSA alone, and fPSA alone, but
not than the AUC of 3D-MRSI alone (Table 1(A)).
Table 1(A) summarizes the sensitivity, specificity, and
predictive values for all individual variables and for the
multivariate model. Of the individual variables, 3D-
MRSI had the highest sensitivity (89.7%), specificity
(92.9%), PPV (85.4%), and NPV (95.1%). Combining all
variables yielded higher sensitivity (91.0%), specificity
(94.6%), PPV (88.8%), and NPV (95.8%) than 3D-MRSI
alone, although differences were not statistically signifi-
cant.
3.2. Transition Zone (TZ)
Among patients with negative biopsies, at MRI 97.4%
(182/191) had grade 1-2 lesions and none had grade 4-5
lesions and at 3D-MRSI, 95.3% (182/191) had grade 1 -
2 lesions, 3.7% (7/191) had grade 3 lesions, 1.1% (2/191)
had grade 4 lesions, and none had grade 5 lesions.
Among patients with PCa, at MRI 64.7% (22/34) had
grade 2 lesions, 35.3% (12/34) had grade 3 or 4 lesions,
and none had grade 5 lesions and at 3D-MRSI 44.1%
(15/34) had grade 2 lesions and 55.9% (19/34) had grade
3 - 5 lesions (Table 2(B)).
The AUC of MRI and 3D-MRSI were 0.758 and 0.813,
respectively (Figure 3). OR are summarized in Table 1(B).
The AUC of the model combining all variables was
0.844 (Figure 3), which is significantly greater than the
AUC of tPSA alone or %fPSA alone but not than the

J. COMET-BATLLE ET AL. 203
0.00 0.25 0.50 0.75 1.00
Sensitivity
0.00 0.25 0.50 0.75 1.00
1-Specificity
MSI+MRSI+tPSA+fPSA (AUC=0.845)
MRSI (AUC=0.813)
MRI (AUC=0.758)
fPSA (AUC=0.705)
tPSA (AUC=0.745)
No discrimination line
Figure 3. Prostate transition zone. Receiver operating char-
acteristic (ROC) curves for the predictive variables mag-
netic resonance imaging (MRI), magnetic resonance spec-
troscopy (3D-MRSI), total prostate-specific antigen (tPSA),
free-to-total prostate-specific antigen ratio (fPSA), and the
combination of all four variables. The overall accuracy of
each model is specified in the area under the corresponding
ROC curves (AUC).
AUC of MRI alone or 3D-MRSI alone (Table 1(B)).
The sensitivity (55.9%) and NPV (92.4%) of 3D-
MRSI were similar to those of the other variables, but its
specificity (95.3%) and PPV (67.9%) were significantly
higher. The model combining all variables had a signifi-
cantly higher sensitivity (76.5%) than MRSI alone, al-
though its specificity (83.2%) and PPV (44.8%) were sig-
nificantly lower. The NPV (95.2%) of the combined mo-
del was similar to that of 3D-MRSI alone (Table 1(B)).
3.3. Gleason versus MRI and 3D-MRSI
Table 2(C) shows the relation between MRI/3D-MRSI
and Gleason score. Both MRI and 3D-MRSI were posi-
tively associated with the Gleason score (G = 0.431; p =
0.001 and G = 0.367; p = 0.005, respectively). In patients
with Gleason ≤ 6 (up to 3 + 3), 72.7% (16/22) had high
grade 3D-MRSI lesions (grade 3-5). In patients with
Gleason 7 (3 + 4 or 4 + 3), 84.8% (28/33) had high grade
3D-MRSI lesions, and in patients with Gleason 8-10,
93.1% (27/29) had grade 3D-MRSI lesions.
4. Discussion
Several studies have found benefits from using endorec-
tal MRI and 3D-MRSI in diagnosing and staging PCa
[7,10]. In a meta-analysis of MRI and 3D-MRSI in the
diagnosis of PCa, Umbehr et al. [11] concluded that al-
though many studies had encouraging results [12-20],
larger studies were necessary to confirm its cost-effecti-
veness. They reported sensitivities and specificities from
several studies ranging from 58% to 82% and from 78%
to 91%, respectively, depending on the patient’s risk for
PCa. In the present study, we found a high sensitivity and
specificity for MRI/3D-MRSI. Although MRI/3D-MRSI
was more accurate in the PZ than in the TZ, the accuracy
in the TZ is still good and is comparable to the accuracy
reported for other series. This is probably related to the
presence of experienced radiologists in specialized cen-
ters.
D’Amico et al. [21] reported the impact of including
MRI in a multivariate analysis to predict extraprostatic
cancer. MRI has also been advocated for planning sur-
gery and deciding whether to resect the neurovascular
bundle [22]. The European guidelines on PCa state that
MRI could be accurate in staging PCa and that 3D-MRSI
increases the accuracy of tumor localization and corre-
lates with the Gleason score [23]. They also suggest us-
ing MRI/3D-MRSI in patients with previous negative
biopsies with persistent clinical suspicion of PCa [24],
but the indications are still very vague regarding their use
for early diagnosis of PCa.
The rationale behind evaluating the results according
to the topographic location of PCa comes from the dif-
ferences we observed in the accuracy for the detection of
PCa depending on the site (TZ or PZ), and our goal was
to evaluate the usefulness of MRI/3D-MRSI combined
with clinical parameters in selecting candidates for bi-
opsy according to the risk of having PCa, either in the PZ
or the TZ. Thus, we focused on whether MRI/3D-MRSI
is able to avoid biopsies in patients with elevated tPSA.
In the present study, tPSA ranged from 0.16 ng/ml in a
patient with a previous adenomectomy with a microfocus
of PCa in the pathologic specimen to 71.00 ng/ml in an-
other with locally advanced PCa, but the median tPSA
was relatively low (7.81 ng/ml); nevertheless, tPSA was
not predictive of PCa. The model incorporating MRI,
3D-MRSI, and %fPSA was significantly more accurate
in predicting PCa (AUC = 0.965) than other models us-
ing MRI alone (AUC = 0.857) or %fPSA alone (AUC =
0.640). In the TZ, the same model was less accurate
(AUC = 0.845), but this result is still good, considering
the heterogeneity of the TZ and the low detection rates of
TRUS biopsy and TURP in the TZ [25,26].
Our study has two major limitations: First, is that bi-
opsy results might not be a good representation of the
real number of patients that have PCa; therefore, the sen-
sitivity of MRI/3D-MRSI measured against this standard
would lack validity. Nevertheless, this is a detection
study, and the patients in our series were followed up
from 6 months to several years, and at least 3 biopsies
were performed to these patients if no cancer was found,
to rule out PCa as far as possible. The second one is the
limited correlation between MRI/3D-MRSI and TRUS,

J. COMET-BATLLE ET AL. 204
to ensure that cores were taken from the suspicious MRI
area. For this reason, when performing the biopsies for
this study, radiologists and urologists worked together to
ensure as much as possible the best location of lesions
detected at MRI/MRSI.
We confirm the relation between 3D-MRSI and Glea-
son score reported by Zakian et al. [27], who suggested
the potential of 3D-MRSI for noninvasive assessment of
PCa aggressiveness.
We aimed to evaluate the predictive value of MRI/3D-
MRSI in patients with suspected PCa and to correlate
MRI/3D-MRSI findings with the clinical and pathologi-
cal findings during long-term follow-up to establish the
indication for MRI/3D-MRSI in these patients. We sug-
gest patients with the following findings undergo TRUS
biopsy:
1) Grade 4 or 5 3D-MRSI.
2) Grade 3 3D-MRSI and grade 3, 4, or 5 MRI.
Finally, we are aware that multiparametric MRI has
the advantages of being quicker and more widely avail-
able [28] than 3D-MRSI, which is time consuming and
requires special software. However, MRI/3D-MRSI is
cost-effective because it is less expensive and has similar
accuracy to diffusion for PCa detection in the PZ and
may be more accurate than multiparametric MRI in the
TZ [29]. Thus, MRI/3D-MRSI remains a good tool for
centers with experience.
5. Conclusions
1) In patients with an elevated tPSA and fPSA < 15%,
suspicious lesions at MRI/3D-MRSI must be biopsied.
Negative biopsy results call for follow-up including re-
peat biopsies
2) In patients without suspicious lesions at 3D-MRSI,
biopsies for high tPSA might be unnecessary.
3) Negative MRI/3D-MRSI findings suggest that sig-
nificant PCa, either in volume or in grade, is unlikely;
therefore, MRI/3D-MRSI may obviate subsequent biop-
sies in patients with high PSA or candidates for active
surveillance.
6. Acknowledgements
This research was partially supported by the Spanish Mi-
nistry of Science and Innovation under project CODA-
RSS (Ref. MTM2009-13272) and by the Agència de
Gestió d’Ajuts Universitaris i de Recerca of the Gener-
alitat de Catalunya (Ref. 2009SGR424). The authors also
thank John Giba for his help with the English language.
REFERENCES
[1] I. M. Thompson, D. K. Pauler and P. J. Goodman,
“Prevalence of Prostate Cancer among Men with a Pros-
tate-Specific Antigen Level < or =4.0 ng per Milliliter,”
The New England Journal of Medicine, Vol. 350, No. 22,
2004, pp. 2239-2246. doi:10.1056/NEJMoa031918
[2] C. G. Arcangeli, D. K. Ornstein and D. W. Keetch, “Pros-
tate-Specific Antigen as a Screening Test for Prostate
Cancer. The United States Experience,” Urologic Clinics
of North America, Vol. 24, No. 2, 1997, pp. 299-306.
doi:10.1016/S0094-0143(05)70376-1
[3] G. L. Andriole and W. J. Catalona, “Using PSA to Screen
for Prostate Cancer. The Washington University Experi-
ence,” Urologic Clinics of North America, Vol. 20, No. 4,
1993, pp. 647-651.
[4] J. B. Shah, A. C. Reese and J. M. McKiernan, “PSA Up-
dated: Still Relevant in the New Millennium?” European
Urology, Vol. 47, No. 4, 2005, pp. 427-432.
doi:10.1016/j.eururo.2004.12.020
[5] A. W. Roddam, M. J. Duffy and F. C. Hamdy, “Use of
Prostate-Specific Antigen (PSA) Isoforms for the Detec-
tion of Prostate Cancer in Men with a PSA Level of 2 - 10
ng/ml: Systematic Review and Meta-Analysis,” European
Urology, Vol. 48, No. 3, 2005, pp. 386-399.
doi:10.1016/j.eururo.2005.04.015
[6] J. Scheidler, H. Hricak and D. B. Vigneron, “Prostate
Cancer: Localization with Three-Dimensional Proton MR
Spectroscopic Imaging—Clinicopathologic Study,” Radi-
ology, Vol. 213, No. 2, 1999, pp. 473-480.
[7] A. E. Wefer, H. Hricak and D. B. Vigneron, “Sextant
Localization of Prostate Cancer: Comparison of Sextant
Biopsy, Magnetic Resonance Imaging and Magnetic Re-
sonance Spectroscopic Imaging with Step Section Histo-
logy,” Journal of Urology, Vol. 164, No. 2, 2000, pp.
400-404. doi:10.1016/S0022-5347(05)67370-3
[8] J. Kurhanewicz, D. B. Vigneron and H. Hricak, “Three
Dimensional H-1 MR Spectroscopic Imaging of the in
Situ Human Prostate with High (0.24 - 0.7 cm3) Spatial
Resolution,” Radiology, Vol. 198, No. 3, 1996, pp. 795-
805.
[9] K. Okamura, H. Takaba and O. Kamihira, “Determination
of the Relative Probability for Prostate Cancer to Avoid
Unnecessary Biopsies,” International Journal of Urology,
Vol. 12, No. 4, 2005, pp. 346-352.
doi:10.1111/j.1442-2042.2005.01056.x
[10] J. Nakashima, A. Tanimoto and Y. Imai, “Endorectal
MRI for Prediction of Tumour Site, Tumour Size, and
Local Extension of Prostate Cancer,” Journal of Urology,
Vol. 64, No. 1, 2004, pp. 101-105.
doi:10.1016/j.urology.2004.02.036
[11] M. Umberh, L. M. Bachmann and U. Held, “Combined
Magnetic Resonance Imaging and Magnetic Resonance
Spectroscopy Imaging in the Diagnosis of Prostate Can-
cer: A Systematic Review and Meta-Analysis,” European
Urology, Vol. 55, No. 3, 2009, pp. 575-591.
doi:10.1016/j.eururo.2008.10.019
[12] J. S. P Yuen, C. H. Thng and P. H. Tan, “Endorectal
Magnetic Resonance Imaging and Spectroscopy for the
Detection of Tumor Foci in Men with Prior Negative
Transrectal Ultrasound Prostate Biopsy,” Journal of Uro-
logy, Vol. 171, No. 4, 2004, pp. 1482-1486.

J. COMET-BATLLE ET AL. 205
doi:10.1097/01.ju.0000118380.90871.ef
[13] D. Amsellem-Ouazana, P. Younes and S. Conquy, “Ne-
gative Prostatic Biopsies in Patients with a High Risk of
Prostate Cancer. Is the Combination of Endorectal MRI
and Magnetic Resonance Spectroscopic Imaging (MRSI)
a Useful Tool? A Preliminary Study,” European Urology,
Vol. 47, No. 5, 2005, pp. 582-586.
doi:10.1016/j.eururo.2005.01.015
[14] A. Shukla-Dave, H. Hricak and N. Ishill, “Correlation of
MR Imaging and MR Spectroscopic Imaging Findings
with Ki-67, Phospho-Akt, and Androgen Receptor Ex-
pression in Prostate Cancer,” Radiology, Vol. 250, No. 3,
2009, pp. 803-807. doi:10.1148/radiol.2503080473
[15] S. Ikonen, P. Kärkkainen and L. Kivisaar, “Magnetic
Resonance Imaging of Prostatic Cancer: Does Detection
Vary between High and Low Gleason Score Tumors?”
Prostate, Vol. 43, No. 1, 2000, pp. 43-48.
doi:10.1002/(SICI)1097-0045(20000401)43:1<43::AID-P
ROS6>3.0.CO;2-S
[16] Y. Kubota, S. Kamei and M. Nakano, “The Potential Role
of Prebiopsy Magnetic Resonance Imaging Combined
with Prostate Specific Antigen Density in the Detection
of Prostate Cancer,” International Journal of Urology,
Vol. 15, No. 4, 2008, pp. 322-327.
doi:10.1111/j.1442-2042.2008.01991.x
[17] L. Wang, H. Hricak and M. Kattan, “Combined Endorec-
tal and Phased-Array MRI in the Prediction of Pelvic
Lymph Node Metastasis in Prostate Cancer,” American
Journal of Roentgenology, Vol. 186, No. 3, 2006, pp.
743-748. doi:10.2214/AJR.04.1682
[18] J. Q. Zhang, K. R. Loughlin and K. H. Zou, “Role of
Endorectal Coil Magnetic Resonance Imaging in Treat-
ment of Patients with Prostate Cancer and in Determining
Radical Prostatectomy Surgical Margin Status: Report of
a Single Surgeon’s Practice,” Journal of Urology, Vol. 69,
No. 6, 2007, pp. 1134-1137.
doi:10.1016/j.urology.2007.01.094
[19] A. P. S. Kirkham, M. Emberton and C. Allen, “How
Good Is MRI at Detecting and Characterising Cancer
within the Prostate?” European Urology, Vol. 50, No. 6,
2006, pp. 1163-1175. doi:10.1016/j.eururo.2006.06.025
[20] N. G. Costouros, F. V. Coakley and A. C. Westphalen,
“Diagnosis of Prostate Cancer in Patients with an Ele-
vated PSA Level: Role of Endorectal MRI and MR Spec-
troscopic Imaging,” American Journal of Roentgenology,
Vol. 188, No. 3, 2007, pp. 812-816.
doi:10.2214/AJR.06.0165
[21] A. V. D’Amico, R. Whittington and M. Schnall, “The
Impact of the Inclusion of Endorectal Coil Magnetic
Resonance Imaging in a Multivariate Analysis to Predict
Clinically Unsuspected Extraprostatic Cancer,” Cancer,
Vol. 75, No. 9, 1995, pp. 2368-2372.
doi:10.1002/1097-0142(19950501)75:9<2368::AID-CNC
R2820750929>3.0.CO;2-#
[22] H. Hricak, L. Wang and D. C. Wei, “The Role of Preo-
perative Endorectal Magnetic Resonance Imaging in the
Decision Regarding Whether to Preserve or Resect Neu-
rovascular Bundles during Radical Retropubic Prostatec-
tomy,” Cancer, Vol. 100, 2004, pp. 2655-2663.
doi:10.1002/cncr.20319
[23] “European Guidelines on Prostate Cancer of the European
Association of Urology,” 2012.
[24] “European Guidelines on Prostate Cancer of the European
Association of Urology,” 2012.
[25] R. Zigeuner, L. Schips and K. Lipsky, “Detection of
Prostate Cancer by TURP or Open Surgery in Patients
with Previously Negative Transrectal Prostate Biopsies,”
Urology, Vol. 62, No. 5, 2003, pp. 883-887.
doi:10.1016/S0090-4295(03)00663-0
[26] A. E. Pelzer, J. Bektic and A. P. Berger, “Are Transition
Zone Biopsies Still Necessary to Improve Prostate Cancer
Detection? Results from the Tyrol Screening Project,”
European Urology, Vol. 48, No. 6, 2005, pp. 916-921.
doi:10.1016/j.eururo.2005.07.012
[27] K. L. Zakian, K. Sircar and H. Hricak, “Correlation of
Proton MR Spectroscopic Imaging with Gleason Score
Based on Step Section Pathologic Analysis after Radical
Prostatectomy,” Radiology, Vol. 234, No. 3, 2005, pp.
804-814. doi:10.1148/radiol.2343040363
[28] L. Dickinson, H. U. Ahmed and C. Allen, “Magnetic
Resonance Imaging for the Detection, Localization and
Characterisation of Prostate Cancer: Recommendations
from a European Consensus Meeting,” European Urology,
Vol. 59, No. 4, 2011, pp. 477-494.
doi:10.1016/j.eururo.2010.12.009
[29] J. C. Vilanova, C. Barcelo and J. Comet, “Usefulness of
Prebiopsy Multifunctional and Morphologic MRI Com-
bined with Free to Total Prostate Specific Antigen Ratio
in the Detection of Prostate Cancer,” American Journal of
Roentgenology, Vol. 196, No. 6, 2011, pp. 715-722.
doi:10.2214/AJR.10.5700