Performance characteristics of multiparametric-MRI at a non-academic hospital
using transperineal template mapping biopsy as a reference standard
Edwin Michael Chau
, Manit Arya
, Neophytos Petrides
, Zaid Aldin
, Jolanta McKenzie
, Jaspal Virdi
, Hashim Uddin Ahmed
, Veeru Kasivisvanathan
Division of Surgery and Interventional Science, University College London, United Kingdom
Department of Urology, University College London Hospital, United Kingdom
Department of Urology, Princess Alexandra Hospital, United Kingdom
Department of Pathology, Princess Alexandra Hospital, United Kingdom
Department of Radiology, Princess Alexandra Hospital, United Kingdom
Division of Surgery, Department of Surgery and Cancer, Imperial College London, United Kingdom
Imperial Urology, Imperial Healthcare NHS Trust, United Kingdom
Received 4 January 2018
Accepted 7 January 2018
Available online 31 January 2018
Magnetic resonance imaging
Predictive value of tests
Objectives: To evaluate diagnostic accuracy of mpMRI in a non-academic hospital using transperineal
template prostate mapping (TPM) biopsy as a reference standard. Secondary objectives included
evaluating why mpMRI missed signiﬁcant cancer.
Materials and methods: 101 men received pre-biopsy mpMRI and TPM-biopsy over 16 months. Disease
status was assigned at hemigland level. Primary histological deﬁnition of clinical signiﬁcance was
Gleason grade >/¼4þ3 or maximum cancer core length (MCCL) >/¼6 mm. Positive mpMRI was
deﬁned as Prostate Imaging Reporting and Data System (PI-RADS) score >/¼3.
Results: Median age 69 (IQR 62e76). Median PSA 7 ng/ml (IQR 4.6e9.8). mpMRI had sensitivity 76.9%,
speciﬁcity 60.7%, PPV 40.4% and NPV 88.3% at primary deﬁnitions. For detecting any Gleason >/¼7
mpMRI had sensitivity 73.2%, speciﬁcity 60.3%, PPV 41.4% and NPV 85.4%. Mean MCCL was lower where
signiﬁcant cancer was missed compared to those correctly identiﬁed (5.8 mm versus 7.7 mm respec-
tively, p ¼0.035).
Conclusion: mpMRI performance characteristics were very encouraging when compared to contemporary
clinical trials. In a non-academic hospital setting, nega tivempMRI was just as good at ruling-out signiﬁcant
disease, though the ability of positive mpMRI to accurately detect signiﬁcant disease was lower. An
mpMRI-guided diagnostic pathway should be accompanied by appropriate mpMRI protocol optimisation,
training, and quality control.
©2018 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Transrectal ultrasound (TRUS) guided prostate biopsy is the
standard of care for prostate cancer diagnosis in many countries .
It is routinely carried out under local anaesthetic and is relatively
easily learnt, taught and applied, making it a practical diagnostic
strategy. However, it has several recognised limitations and is
prone to random and systematic error . Anterior lesions are
frequently missed, reducing accuracy . Additionally, they can
lead to urosepsis in 1e6% .
The use of magnetic resonance imaging (MRI) in the prostate
cancer pathway has seen growing interest due to advances in
technology using a multiparametric approach (mpMRI). This
involves T1 and T2 weighted images (T2W) combined with func-
tional imaging sequences such as diffusion weighted imaging
(DWI) and dynamic contrast enhancement (DCE) [5,6]. If biopsy
could be avoided in men with negative mpMRI then routine use of
pre-biopsy mpMRI could be a cost-effective strategy compared to
TRUS-biopsy . However, as a relatively novel modality, routine
integration of pre-biopsy mpMRI into national diagnostic cancer
pathways has yet to occur.
*Corresponding author. Urology Research Group, Room 4.23, 4th Floor, 132
Hampstead Road, London, NW1 2PT, United Kingdom.
E-mail address: email@example.com (V. Kasivisvanathan).
These authors share joint senior authorship.
Contents lists available at ScienceDirect
International Journal of Surgery Open
journal homepage: www.elsevier.com/locate/ijso
2405-8572/©2018 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://
International Journal of Surgery Open 10 (2018) 66e71
Data from experienced academic centres and contemporary
clinical trials show the negative predictive value (NPV) for detec-
tion of signiﬁcant cancer for mpMRI ranges from 72 to 92% [8e11 ]
and targeted-only approaches have been shown to detect similar
amounts of signiﬁcant cancer to systematic biopsy [12,13].
Randomised studies have shown that MRI performance may be
inﬂuenced by whether the centre was a dedicated high volume
mpMRI academic centre or a non-academic centre, with better
performance of an MRI-guided pathway demonstrated in the aca-
demic centre  than outside of one . It is thus known that
optimisation of MRI scanners and the centre's experience has an
important role in mpMRI performance as a diagnostic tool .
However, mpMRI has not been validated in non-tertiary referral
(“non-academic”) centres against a thorough reference standard of
transperineal template mapping biopsy (TPM).
The primary objective of this study was to evaluate the diag-
nostic accuracy of mpMRI in a non-tertiary referral centre using
TPM biopsy as a reference standard. Secondary objectives were to
assess: the additional value of DCE and high b-values on DWI in
detecting cancer and to explore reasons why mpMRI missed
2. Material and methods
Princess Alexandra Hospital (PAH), a non-academic hospital,
receiving the majority of its referrals for men with suspected
prostate cancer directly from family doctors.
2.2. Patient cohort
All consecutive men who had a TPM biopsy between January 1st,
2015 and April 30th, 2016 were identiﬁed from the histopathology
database. The population consisted of a representative cohort of all
men indicated for prostate biopsy including: 1) biopsy naïve men
with suspicion of prostate cancer, 2) men with previous negative
biopsy but continued suspicion of prostate cancer and 3) men with
known low risk prostate cancer conﬁrmed on a previous biopsy on
active surveillance. All men underwent prostate mpMRI and went
on to biopsy regardless of mpMRI ﬁndings. Men were excluded if
the mpMRI was carried out at a different institution or if it
was known in advanced that major MRI artefact would be present
(e.g. pelvic metalwork).
2.3. Transperineal biopsy
TPM biopsy was performed under general anaesthesia using a
modiﬁed Barzell technique, reported previously .Biopsycores
were taken approximately every 5 mm on the transperineal grid,
aiming for a sampling density of 1 biopsy per ml of tissue. Biopsy
cores were potted separately into one of 12 pots. Where mpMRI
identiﬁed a suspicious lesion, additional targeted biopsies were
taken using visual registration technique . One of three experi-
enced surgeons with threeto six years of experience in transperineal
prostate biopsy carried out the procedures.
2.4. Magnetic resonance imaging
mpMRI was performed with one of two scanners (1.5T Siemens
Avanto and 1.5T Siemens Essenza). Sequences included T2W and
DWI imaging for all patients, DCE was introduced after January
2015. Contrast used was 15 ml Dotarem
administered at 3 mls/sec (concentration 279.32 mg/ml). All cases
used a pelvic phased array coil without endorectal coils.
mpMRIs were reported by one of three consultant radiologists
with experience in prostate mpMRI ranging from ﬁve to twelve
years. Prostate lesions were scored using ﬁve-level PI-RADS
scale (1ecancer highly unlikely, 2ecancer unlikely, 3eequivocal,
4ecancer likely, 5ecancer highly likely) and scores allocated into 27
sectors. Scoring prior to October 2015 was performed using PI-
RADSv1 . After this, PI-RADSv2 guidelines were adopted .
Dedicated high b-values (>/¼1000) were introduced from August
2015. Detailed sequence parameters are shown in Supplementary
2.5. Prostate specimens
Specimens were analysed according to guidelines set by the
Royal College of Pathologists, UK .
2.6. Clinical signiﬁcance
Our primary objective was based on using the validated UCL
deﬁnition 1 (maximum cancer core length [MCCL] >/¼6mmof
any grade or any amount of Gleason grade >/¼4þ3) and PI-RADS
score >/¼3 on mpMRI [10,20]. As there is no accepted universal
deﬁnition of clinically signiﬁcant cancer results were reported
secondarily according to UCL deﬁnition 2 (MCCL >/¼4mmor
Gleason grade >/¼3þ4) and any amount of Gleason grade >/¼7.
2.7. Re-review of mpMRI
False negative (FN) mpMRIs were re-reviewed by a senior
consultant radiologist with pathology results to explore reasons
why the initial report was deemed PI-RADS 1e2. Differences in
characteristics (PSA level, PSA density, gland volume, total cancer
core length (TCCL), and MCCL) between patients with FN and true
positive (TP) mpMRIs were compared to identify features that
might predict missing cancer.
Prostates were analysed on hemigland level as consistent with
previous studies in this ﬁeld .
Statistical analysis was conducted using Microsoft Excel and
SPSS version 22 (release 126.96.36.199). 2 2 tables to compare presence
or absence of clinically signiﬁcant cancer were created. Sensitivity,
speciﬁcity, positive predictive value (PPV), NPV, and difference
between proportions with 95% CI were calculated where appro-
priate. Independent T-tests were performed between TP and FN
This project was deemed exempt from ethics committee
approval by the research and development department at PAH.
3.1. Study population details
122 men were identiﬁed who underwent TPM within the study
period. 21 were excluded (1 had mpMRI from another site, 5 had
major artefacts from metalwork, and 15 did not have a pre-biopsy
mpMRI). Median age was 69, median PSA was 7.0 ng/ml and
median prostate volume was 42 ml 24/101 (24%) had no mpMRI
lesion; 76/101 (75%) had a PI-RADS score of >/¼3(Table 1).
Overall detection of all cancer on TPM biopsy was 78/101 (77%).
41/101 (41%) had cancer diagnosed with UCL deﬁnition 1; 57/101
E.M. Chau et al. / International Journal of Surgery Open 10 (2018) 66e71 67
(56%) with UCL deﬁnition 2; and 43/101 (43%) with any Gleason
>/¼7. Breakdown of cancer detected is given in Table 2.
3.2. mpMRI validity
At primary deﬁnitions of clinical signiﬁcance, mpMRI achieved
sensitivity 76.9% (95% CI 66e88), speciﬁcity 60.7% (95% CI 53e69),
PPV 40.4% (95% CI 31e50) and NPV 88.3% (95% CI 82e95). The
performance characteristics of mpMRI according to varied histo-
logical thresholds for clinically signiﬁcant disease is summarised in
3.3. Sub-group analysis: dynamic contrast enhancement
No difference in performance characteristics were shown be-
tween scans with and without DCE (Table 4).
3.4. Subgroup analysis: sequence parameters
46 men had mpMRI scans with dedicated high b-value as part
of the DWI sequences and 55 men had scans prior to use of high
b-values. Addition of high b-values demonstrated a higher speci-
ﬁcity but lower sensitivity (summarised in Table 5).
3.5. False negative mpMRI
10/12 (83%) hemiglands with signiﬁcant cancer (UCL deﬁnition
1) missed by mpMRI had lesions located in the apex only and 2/12
(17%) had lesions extending through both apex and base of the
prostate. No missed cancer was found isolated to the base only. 4/12
(33%) lesions were visible on re-review and were missed on initial
reporting (all scoring PI-RADS 1 initially); 6/12 (50%) were difﬁcult
to accurately visualise on re-review due to heterogeneous gland
appearance; 1/12 was not visible at all (8%); and 1/12 (8%) was due
to coding of a midline TPM sector as bilateral disease, therefore no
lesion was actually missed.
The key difference in men who had signiﬁcant disease missed by
mpMRIs compared to those who had correctly identiﬁed lesions
(Table 6) was mean MCCL, which was signiﬁcantly lower in those
cancers missed on mpMRI (means 5.8 mm versus 7.7 mm,
difference 1.9 mm, p ¼0.035).
4.1. Summary of main ﬁndings
In summary, our study demonstrates that in the context of a
non-academic hospital, mpMRI has good performance character-
istics for the detection of clinically signiﬁcant cancer with high
sensitivity 76.9% and NPV 88.3%. This is encouraging for the
adoption of an MRI-inﬂuenced diagnostic pathway outside of
academic centres. As with other studies, speciﬁcity 60.7% and PPV
40.4% were low indicating the need for histological veriﬁcation of a
suspicious area on mpMRI. We also explored possible reasons for
mpMRI missing clinically signiﬁcant cancer and showed that when
mpMRI missed cancer, it tended to be low volume disease, with low
maximum cancer core length.
4.2. Clinical implications
mpMRI has been proposed as a triage test for men with sus-
pected prostate cancer, suggesting that men with negative mpMRIs
could avoid biopsy altogether [10,12]. Whilst results seen from the
literature are primarily from tertiary referral centres or clinical trial
settings, there is a distinct lack of results from centres outside these
settings. It is in these pragmatic settings that the validity of
mpMRI needs to be proven to consider widespread adoption of this
strategy as a primary diagnostic approach for suspected cancer.
Study population details.
Total number of patients 101
Median age (IQR) 69 (62e76)
Median ml prostate volume (IQR) 42 (30e54)
Median ng/ml PSA (IQR) 7.0 (4.6e9.8)
Median sampling density - number of biopsy cores taken/ml prostate tissue (IQR) 0.94 (0.77e1.3)
Number of mpMRI with contrast enhanced sequences (%) 47 (46.5)
Prior biopsy status (%)
- Previous positive 64 (63.4)
- Previous negative 12 (11.9)
- Biopsy naive 25 (24.8)
MRI result (%)
- PI-RADS score 1 - 2 25 (24.8)
- PI-RADS score 3 32 (31.7)
- PI-RADS score 4 23 (22.8)
- PI-RADS score 5 21 (20.8)
Cancer detection results of transperineal template biopsy.
Number of men with clinically signiﬁcant cancer (%)
- UCL deﬁnition 1 (Gleason grade >/¼4þ3 and/or maximum cancer core length >/¼6 mm) 41 (40.6)
- UCL deﬁnition 2 (Gleason grade >/¼3þ4 and/or maximum cancer core length >/¼4 mm) 57 (56.4)
Biopsy result (%)
- Gleason grade 3 þ3 35 (34.7)
- Gleason grade 3 þ4 31 (30.7)
- Gleason grade 4 þ3 6 (5.9)
- Gleason grade 4 þ4 6 (5.9)
- Benign 15 (14.9)
- ASAP or PIN
ASAPeatypical small acinar proliferation, PINeprostatic intraepithelial neoplasia.
E.M. Chau et al. / International Journal of Surgery Open 10 (2018) 66e7168
Our results show that approximately 12% of clinically signiﬁcant
cancers (UCL deﬁnition 1) would be missed if decisions to avoid
biopsy were based on negative mpMRI alone. The value of a
negative mpMRI is similar to the PROMIS trial which demonstrated
a NPV 89%. The value of a negative mpMRI to rule out signiﬁcant
cancer at the less stringent UCL deﬁnition 2 is also similar to
PROMIS, with NPV 80%, compared to PROMIS which demonstrated
NPV 72%. These results are very encouraging as they demonstrate
that mpMRI can have good performance characteristics in a prag-
matic setting outside of a tightly regulated clinical trial.
Whilst missing 12e20% (depending on the deﬁnition used) of
clinically signiﬁcant disease may seem high, one should consider
this in the context of what men would otherwise get. The standard
of care for suspected prostate cancer in many countries is TRUS-
guided biopsy, which commonly has an NPV lower than that seen
for mpMRI in this study, ranging from 36 to 74% for all cancer
detected [11,21e23]. In this context, provided that men with
negative mpMRIs are kept under PSA surveillance it would appear
that mpMRI could have a role in triaging for biopsy. That too,
interpreting a negative MRI in conjunction with a low PSA density
may further help reassure clinicians that avoiding biopsy is safe and
However, when comparing the ability of mpMRI to detect
clinically signiﬁcant disease (UCL deﬁnition 1) and the value of a
positive test result, the results from this study are not as good as
those seen in the PROMIS Trial which demonstrated a sensitivity of
93%. Learning from the re-review of mpMRIs where signiﬁcant
cancer was missed, 33% of the FN hemiglands had lesions missed
initially, which were then visible on re-review. This conﬁrms the
known inter-rater variability  and might support the concept of
non-suspicious mpMRIs getting a double read if decision about
avoiding biopsy is going to be made.
It should also be emphasised that the current study results
reﬂect an on-going optimisation of mpMRI conduct during the
study period. The PROMIS trial on the other hand had dedicated
quality control of mpMRI conduct and training in mpMRI reporting
built in to the study prior to the commencement of the study. So
perhaps this difference is to be expected. This suggests that in order
to obtain the mpMRI sensitivity seen in contemporary clinical trials,
appropriate quality control, optimisation of protocols and training
is necessary. Results observed in the PROMIS trial cannot be
immediately expected by centres developing an mpMRI service and
a period of optimisation should be expected. Future work should
focus on establishing what this training and quality control should
be and how it should be delivered.
In light of the on-going optimisation of mpMRI conduct during
the study we carried out subgroup analyses to explore the effect
that this had. The use of long-b values in mpMRI has been shown to
improve diagnostic performance and dedicated high-b values are
recommended in PI-RADsv2 [5,26]. The beneﬁt of DCE, however, is
not as clear in the literature, with some studies showing no
Performance characteristics of multiparametric-MRI in detecting prostate cancer at radiological threshold of PI-RADS score >/¼3 and varied histological thresholds (95% CI
given in parentheses).
Sensitivity Speciﬁcity PPV NPV
UCL deﬁnition 1 76.9 (66e88) 60.7 (53e69) 40.4 (31e50) 88.3 (82e95)
UCL deﬁnition 2 73.1 (63e83) 66.1 (58e75) 57.6 (48e67) 79.6 (72e87)
Gleason grade >/¼3þ4 73.2 (62e85) 60.3 (52e68) 41.4 (32e51) 85.4 (79e92)
Performance of multiparametric-MRI with and without contrast in detecting prostate cancer using clinically signiﬁcant thresholds of UCL deﬁnition 1 and PI-RADS score >/¼3
(95% CI given in parentheses).
Without contrast With contrast Difference between proportions
Sensitivity 86.2 (74e99) 65.2 (46e85) 21 (2e44)
Speciﬁcity 60.8 (50e72) 60.6 (49e72) 0.2 (15e16)
PPV 44.6 (32e58) 34.9 (21e49) 9.8 (10e29)
NPV 92.3 (85e100) 84.3 (74e94) 8 (4e20)
Mean age 68.09 69 0.91
Mean PSA, ng/ml 9.01 7.14 1.87
Mean prostate volume, ml 42.9 45.0 2.1
Performance of multiparametric-MRI in detecting prostate cancer according to sequence parameters at clinically signiﬁcant thresholds of PI-RADS score >/¼3 and UCL
deﬁnition 1 (95% CI given in parentheses).
No high b-values High b-values Difference between proportions
Sensitivity 87.1 (75e99) 61.9 (41e83) 25.2 (1.3e49)
Speciﬁcity 51.9 (41e63) 70.4 (60e81) 18.5 (3.2e34)
PPV 41.5 (30e54) 38.2 (30e55) 3.3 (17e24)
NPV 91.1 (83e99) 86.2 (77e95) 4.9 (7.3e17)
Mean age 67.3 70 2.7
Mean PSA, ng/ml 8.7 7.5 1.2
Mean prostate volume, ml 45.5 41.9 3.6
Comparison between true positive and false negative multiparametric-MRI results
at clinically signiﬁcant thresholds of PI-RADS score >/¼3 and UCL deﬁnition 1.
True positive False negative Difference
Mean PSA level (ng/ml) 9.4 6.9 2.5 (p ¼0.282)
Mean PSA density (ng/ml/cc) 0.24 0.22 0.02 (p ¼0.694)
Mean Gland volume (cc) 41.7 35.4 6.3 (p ¼0.299)
Mean TCCL (mm) 23.7 11.6 12.1 (p ¼0.152)
Mean MCCL (mm) 7.7 5.8 1.9 (p ¼0.035)
Bold signiﬁes signiﬁcant result.
E.M. Chau et al. / International Journal of Surgery Open 10 (2018) 66e71 69
advantage [27,28] and others showing that the combination of
sequences improves the performance of the mpMRI . Our data
did not show improved performance of mpMRI with DCE and
whilst the use of high b-values did show higher speciﬁcity, in line
with the literature, their use did result in decreased sensitivity.
Radical prostatectomy (RP) specimens would be an alternative
reference standard for diagnostic validity of mpMRI. This however
would be an imperfect reference standard  because it could only
be carried out in men who have RP. This would represent selection
bias as one could only assess the validity of mpMRI in men with
high risk features of prostate cancer that are recommended for RP.
Instead, TPM was chosen as the reference standard as it has been
shown to have high diagnostic accuracy and can be applied to all
men at risk of prostate cancer, thus reducing selection bias
[20,30,31]. Furthermore, TPM was carried out at a high sampling
density of almost 1 biopsy per ml of tissue in this study.
We acknowledge that the mpMRI protocols in the study were
modiﬁed over time, but this reﬂects continuing development and
optimisation of mpMRI at our centre, which is an essential process
to optimize cancer detection for any centre wishing to adopt
mpMRI. For readers considering adopting their own mpMRI ser-
vices this shows them progressive steps taken. Further, the inﬂu-
ence of changing protocols on the diagnostic performance of
mpMRI was explored and shown to have negligible effect.
In conclusion, mpMRI performance characteristics in the
non-academic setting were very encouraging when compared to
contemporary clinical trials. A negative mpMRI was just as good at
ruling-out clinically signiﬁcant disease, though the ability of a
positive mpMRI to accurately detect clinically signiﬁcant disease
was lower. This supports the adoption of a mpMRI-driven diag-
nostic prostate cancer pathway outside of academic centres,
though this should be accompanied by appropriate mpMRI proto-
col optimisation, training and quality control.
This project was deemed exempt from ethics committee
approval by the research and development department at PAH.
Veeru Kasivisvanathan is funded by a Doctoral Research
Fellowship from the National Institute for Health Research. Mark
Emberton’s research is supported by core funding from the United
Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL
Biomedical Research Centre. He was awarded NIHR Senior Inves-
tigator in 2015. The views expressed in this publication are those of
the author(s) and not necessarily those of the NHS, the National
Institute for Health Research or the Department of Health. Hashim
Ahmed receives funding from the Medical Research Council (UK).
Study design: Manit Arya, Zaid Aldin, Veeru Kasivisvanathan,
Data collection: Edwin Michael Chau, Neophytos Petrides, Zaid
Data analysis: Edwin Michael Chau, Veeru Kasivisvanathan.
Writing: Edwin Michael Chau.
Critical revision of manuscript: Manit Arya, Zaid Aldin, Jolanta
McKenzie, Mark Emberton, Jaspal Virdi, Hashim Uddin Ahmed,
Supervision: Manit Arya, Zaid Aldin, Jolanta McKenzie, Mark
Emberton, Jaspal Virdi, Hashim Uddin Ahmed, Veeru Kasivisvanathan.
Obtaining funding: Veeru Kasivisvanathan.
Conﬂicts of interest statement
Hashim Ahmed receives funding from Sonacare Medical,
Sophiris, and Trod Medical for other trials. Travel allowance
was previously provided from Sonacare. Mark Emberton has stock
interest in Nuada Medical Ltd. He is also a consultant to Steba
Biotech and GSK. He receives travel funding from SanoﬁAventis,
Astellas, GSK, and Sonacare. He previously received trial funding or
resources from GSK, Steba Biotech and Angiodynamics and receives
funding for trials from Sonacare Inc, Sophiris Inc, and Trod Medical.
The other authors declare no competing interests.
Research registration number
Research registry 2856.
Appendix A. Supplementary data
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