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MRI Assisted Stereotactic Biopsy (MAST) in
Patients with Elevated Prostate Cancer Risk and Previous Negative Biopsy
Gabriella Ghanem1, Danny Vesprini1,2, Masoom A Haider3, Laurent Milot3, Jack Barkin4, Petar Erdeljan5, Shawn Soon5 and Andrew Loblaw1,2,6*
1Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada
2Department of Radiation Oncology, University of Toronto, Canada
3Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Canada
4Division of Urology, Humber River Regional Hospital, Canada
5Division of Urology, The Scarborough Hospital, Canada
6Institute of Health Policy, Measurement and Evaluation, University of Toronto, Canada
Submission: May 05, 2017; Published: July 07, 2017
*Corresponding author: Andrew Loblaw, Institute of Health Policy, Measurement and Evaluation, University of Toronto, Bayview Avenue, Sunnybrook Health Sciences Center, Toronto, ON Canada, Tel: 416 480 4806; Fax: 416 480 6002; Email: andrew.loblawsunnybrook.ca
How to cite this article: Ghanem G, Vesprini D, Haider MA, Milot L, Barkin J, et al. MRI Assisted Stereotactic Biopsy (MAST) in Patients with Elevated Prostate Cancer Risk and Previous Negative Biopsy. JOJ uro & nephron. 2017; 3(4): 555618. DOI:10.19080/JOJUN.2017.03.555618
Purpose: To report on the Sunnybrook experience of MAST biopsies in patients with one or more previous negative prostate biopsies and an elevated prostate cancer risk - referred to as “Discordant PSA” patients.
Materials and methods: 100 patients with an elevated/rising PSA and at least one previous negative prostate biopsy were included in this study. The University of Texas’s PCPTRC was used to articulate the patient’s risk of all cancer and G7+ cancer. All 100 patients received an mpMRI. Patients with a G7+ risk of more than 5% and a nodule on mpMRI were offered a MAST biopsy. Results of the MRI and MAST biopsies were collected and analyzed further.
Results: Overall, 9 out of 24 patients who received a MAST biopsy had clinically significant cancer. Pre-MRI G7+ risk correlated strongly with PI-RADS class (spearman’s rank 0.90, p=0.037). The calculated positive likelihood ratios for PI-RADS 3-5 were 0, 1.2 and 7.1, respectively (positive likelihood ratio= post-test odds/pre-test odds) .
Conclusion: MAST biopsies proved to be a useful method in detecting clinically significant prostate cancer in discordant PSA patients with a PI-RADS class 4-5 lesion. They also proved useful in eliminating unnecessary repeat biopsies in discordant PSA patients.
Keywords: Prostate cancer; Magnetic resonance imaging; Stereotactic biopsy
Prostate cancer is the most commonly diagnosed non-cutaneous malignancy among men in most western countries . In general, an abnormal serum PSA test and/or a suspicious DRE are the first indicators of prostate cancer and warrant further investigations . A TRUSGB is currently the gold standard for confirming prostate cancer diagnoses. PSA tests are characterized by high sensitivity and low specificity whereas TRUSGB are characterized by their low sensitivity and high specificity . In some cases a TRUSGB will not detect any prostate cancer in a patient with an abnormal DRE and/or rising PSA despite the patient going on to be diagnosed with the disease on repeat biopsy or clinical progression (i.e., false negative).
A negative TRUSGB will provide some reassurance by lowering the patient’s risk of having prostate cancer. However, depending on other predictive factors, the patient may still be at substantial risk which can be articulated by nomograms or online calculators [4,5]. We deem these patients “discordant PSA” patients - those with one or more negative prostate biopsies and a persistently elevated prostate cancer risk as determined by PSA and other predictive factors.
Patients who fall into this category have a few options
including: PSA surveillance, repeat TRUSGB, alternative
biomarker assay , initiating a 5-ARI  to elicit a PSA response
or multiparametric magnetic resonance imaging±targeted
TRUSGB is uncomfortable even with the use of periprostatic
anesthetic blocks. Of greater concern, however, are the increasing
risks of the procedure which include urinary tract infections,
hematuria and acute urinary retention . In a populationbased
study of Ontario patients who received TRUSGB, Nam et
al.  reported that the rate of patients readmitted to a hospital
30 days after the procedure increased from 1.0% in 1996 to
4.1% in 2005 . The increase in admission was due to infection
(bleeding and obstruction admissions were stable). In Alberta in
2012, the incidence had risen to 6.3% . Given the diminishing
yield of repeat TRUSGB and increasing complications, a different
approach that may demonstrate a higher positive predictive
value warrants investigation.
PCA3 is a non-protein coding RNA that is over expressed in
prostate cancer, is measureable in urine, does not correlate with
benign prostate volume and is not present in benign prostate
diseases. Quantification of PCA3 mRNA levels can predict
the outcome of prostatic biopsies with a higher specificity in
comparison to PSA . Calculators are available that refine
the risk estimates, including the PCA3, but often a persistently
elevated risk remains . 5-ARIs have been shown to reduce
the risk of low grade prostate cancers in men with discordant
PSAs, but do not reduce the risk of clinically significant disease
(namely intermediate- and high-grade disease)  and may
falsely reassure the patient by lowering his PSA even though
high grade disease might be present. Post-nadir kinetics can
however offer a clue about which patients have underlying highgrade
There is increasing interest in the role of mpMRI in the
diagnosis of prostate cancer. Typical sequences include T1, T2,
Diffusion Weighted imaging with calculation of ADC and DCE.
Prostate tumors (particularly in the peripheral zone) are dark on
T2, show bright/early contrast uptake and have low ADC values
. Lower ADC values have been associated with higher grade
disease . It has been argued that the greatest clinical utility
for an MRI is as a triage test to rule out high grade disease so that
men can avoid unnecessary repeat biopsies . Additionally, MR
imaging has proved a useful imaging technique in discriminating
clinically significant cancers in biopsy naïve prostate cancer
. A MRI-assisted stereotactic biopsy (MAST) biopsy of the
prostate can then be used to confirm the presence or absence of
clinically significant disease.
This study reports the Sunnybrook experience of MAST
biopsies in patients with discordant PSAs. We will describe
the pre-MRI risk of patients referred with discordant PSAs; the
results of the MRIs; the proportion of patients who had a MAST
biopsy and the results of those biopsies.
Patients referred to Sunnybrook Health Sciences Centre
for consideration of a MAST biopsy were considered for this
study. They were referred by their urologists due to one or more
negative biopsies and a rising or elevated PSA (“discordant PSA”).
During their initial consultation, the patient’s risk of prostate
cancer was calculated using the University of Texas’s PCPTRC.
This was done using the patient’s age, ethnicity, DRE result,
latest PSA (including the free to total ratio), family history, and
whether the patient had a previous biopsy.
We included all referred patients who had at least one negative
biopsy and a rising or elevated PSA. Patients were excluded if
they had a history of prostate cancer oral contraindication to
MRI. A convenience sample of one hundred consecutive patients
referred between January 2012 and July 2014 were included in
Data was collected from patient charts and electronic patient
records and used to calculate the risk of prostate cancer (any
grade) and the risk of high grade (Gleason 7 or higher) cancer
using the PCPTRC. PSA was adjusted if the patient was on 5-ARIs.
Information on whether or not the patient had received a PCA3
test was also collected.
MRI was performed on a 3T MR imaging system (Achieva,
Philips Healthcare, Best, The Netherlands) without an endorectal
coil using a 6-channel cardiac surface coil (SENSE, Philips
Healthcare, Best, The Netherlands). Pulse sequence parameters
were as follows: axial, sagittal, and coronal T2-weighted (TR
4000ms, TE 110ms, field of view 22cm, matrix 440x425,
number of acquisitions 1, slice thickness 3mm, slice spacing
0mm); diffusion-weighted (TR 6178ms, TE 61ms, field of view
20cm, matrix 136x136, number of acquisitions 3, 10, and 16, b
values 100, 400, 1000, slice thickness 3mm, slice spacing 0 mm),
and dynamic contrast enhanced imaging (TR 3.9ms, TE 1.8ms,
field of view 26cm, number of acquisitions 4, slice thickness
3mm, slice spacing 0mm. Exams were read by one of two Uro-
Radiologist (MAH, LM). The highest Prostate Imaging-Reporting
and Data System (PI-RADS) score, and the size and location of
nodules were recorded .
Patients were offered biopsies if they had a G7+ risk of more
than 5% and a nodule on MRI. The rationale for this comes from
looking at the risk of complication after a TRUSGB - which is 4.1-
6.3% in patients without cancer [8,9]. Targeted and 12x12mm
core systematic MAST biopsies were done using MR/3D
ultrasound fusion platform (Eigen, Grass Valley). Some patients
who had prostatitis on a previous biopsy had a targeted and 6x22mm core US-guided transperineal biopsies using cognitive
co-registration of MR images. Information on the number of
cores taken, the number of cores involved, Gleason sum, total
surface area, and percentage Gleason 4/5 involvement was
included. Outcomes of patients with nodules who did not go on
to have a MAST biopsy were also included.
The primary outcome was the number of patients diagnosed
with G7+prostate cancer. We also describe the pre-MRI risk of
patients referred with discordant PSAs; the results of the MRIs
(by PI-RADS class); the proportion of patients who had a MAST
biopsy and the results of those biopsies. Simple descriptive
statistics were used to report the results. Spearman’s rank
coefficient was used to correlate pre-MRI G7+ risk and PI-RADS
class. A convenience sample size of 100 was used to get point
estimates of frequencies of the outcomes for planning of future
The clinical and demographic information of the cohort is
summarized in Table 1. Of the 100 patients who received an MRI,
the mean age of the cohort was 64 years (range 46-83 years) and
their median PSA was 8.26ng/ml (range 1.79-54.8ng/ml). These
men had a median of 2 previous negative biopsies (range 1-5).
Four had PCA3 testing. The mean G7+ risk was 25.5% (range
The distribution of PI-RADS score in patients who underwent
an MRI is summarized in Table 2. Sixty-four patients were PIRADS
class 1-2. None were offered biopsy. It should be noted
that one of these patients with a PI-RADS class 2 had an MRI
nodule but his pre-MRI G7+ risk was 7% and he had 2 previous
negative biopsies. After 1.5 years of follow-up his PSA remained
stable and he was discharged to his community Urologist.
Pre-MRI G7+ risk correlated strongly with PI-RADS class
(Table 2), Spearman’s rank 0.90, p=0.037). Of the 19 patients
that were PI-RADS class 3, 9 (47%) had biopsies and all were
negative (Table 2). Eleven of these 19 patients had MRI nodules
(6 had a negative biopsy, 5 were observed). Of the 5 observed,
3 subsequently had repeat MRIs, one of which was PI-RADS
class 4. He had rapidly progressing dementia so it was elected to
observe him clinically.
One of the 5 patients (20%) with PI-RADS class 4 lesions
had cancer (Gleason 8); 9 of 10 patients (90%) of patients with
PI-RADS class 5 lesions had cancer (1 Gleason 6, 8 Gleason 7).
Overall 9 of the 24 patients (37.5%) who received a MAST biopsy
were found to have G7+ prostate cancer. The calculated positive
likelihood ratios for PI-RADS 3-5 were 0, 1.2 and 7.1, respectively
(positive likelihood ratios=post-test odds/pre-test odds) .
In this study we set out to identify how many cases of clinically
significant prostate cancer would be identified in patients with
a discordant PSA and one or more previous negative biopsies
after an MRI and MAST biopsy. Overall we identified 10 prostate
cancers in our 100 patients, 9 of them being clinically significant.
Importantly, however, we were able to avoid repeat biopsies in
76% of patients. Given the discomfort and risk of complications
from TRUSGB [8,9] not to mention that men had a median of
2 previous TRUSGB, we believe this is beneficial for patients.
Since our study was initiated, the UK’s NICE prostate guidelines
recommend considering the use of multi-parametric MRI for
patients with a discordant PSA .
Observing patients with PI-RADS class 1-2 MRIs seems to be
advisable. One long-term study from Itatani et al.  followed
193 patients with negative initial TRUS-guided biopsy findings
and PI-RADS class 1-2 scans for 5 years after their initial MRI.
Only patients with negative findings by digital rectal examination,
MRI, and repeat biopsy and no increase in PSA at 5-year followup
were defined as “clinically negative”. The negative predicted
value for significant prostate cancer was 89.6% .
Although there were only 9 (of 19) patients in our study
with PI-RADS class 3 lesions who received biopsies, all of
these patients had negative biopsies suggesting that biopsying
these men held limited value. Similarly, when Abd-Alazeez and
colleagues looked at PI-RADS 3-5 classes (using systematic
transperineal mapping biopsy, minimum 20 cores, as the gold
standard) the chance of finding G7+ disease was 3/35 (8.6%),
9/23 (39.1%) and 8/11 (72.7%), respectively . We would
recommend that more data should be collected but that following
patients clinically like Itatani et al.  did would seem to offer
a favourable balance between the harms of futile investigation
versus missing clinically significant disease.
One limitation of this study is the lack of follow up in patients
with a nodule and PI-RADS of 3. Of the 7 patients with nodules
who were not biopsied, 3 went on to have repeat MRIs due to
rising PSAs with one having an upgrade to PI-RADS class 4 on
repeat MRI. Follow up has the potential to identify the presence
of clinically significant cancer in these patients. Our study was
smaller than other studies investigating this question [13,16,18],
but most of these are not large enough since the chance of having
PI-RADS class 4-5 is low (only 17% in our study). Larger studies,
particularly with prospective clinical follow-up for patients with
PI-RADS class 1-3, is recommended to improve the confidence of
the likelihood ratio calculations.
In this era of increased cost-consciousness, one might be
critical that 100 MRIs only found 9 cases of cancer in patients
with a discordant PSA and one or more previous negative
biopsies. Of greater concern would be the routine use of mpMRI
in patients who are biopsy naïve. A study by de Rooji et al. 
found that the MRI strategy is initially more expensive but
these costs are compensated for by reducing treatment costs
(in the Netherlands) and avoiding the potential side effects of
unnecessary biopsies. As the treatment and MRI reimbursement
rates factor heavily into these analyses, one would have to
use regional data to determine if this strategy is cost-effective
in one’s local area. We believe currently there is insufficient
evidence to offer MRI screening for prostate cancer using public
In patients with a previous negative prostate biopsy and
elevated cancer risk, mpMRI with stereotactic biopsis for those
with PI-RADS class 4-5 lesions is useful to detect clinically
significant cancers without subjecting patients to unnecessary
biopsies. More work is needed to identify the appropriate
management strategy for these who have PI-RADS class 3 lesions
and the cost-effectiveness of this strategy.