Download Role of multiparametric magnetic resonance imaging (MRI) in focal

Role of multiparametric magnetic resonance
imaging (MRI) in focal therapy for prostate
cancer: a Delphi consensus project
Berrend G. Muller1, Willemien van den Bos1, Maurizio Brausi2, Francois Cornud3,
Paolo Gontero4, Alexander Kirkham5, Peter A. Pinto6, Thomas J. Polascik7,
Ardeshir R. Rastinehad8, Theo M. de Reijke1, Jean J. de la Rosette1, Osamu Ukimura9,
Arnauld Villers10, Jochen Walz11, Hessel Wijkstra1,12 and Michael Marberger13
1
Department of Urology, AMC University Hospital, Amsterdam, The Netherlands, 2Department of Urology, EstenseS.
Agostino Hospital, Modena, Italy, 3Department of Radiology, Cochin Hospital, Paris, France, 4Department of Urology,
Molinette University Hospital, Turin, Italy, 5Department of Radiology, University College Hospital, London, UK,
6
Department of Urology, National Cancer Institute, Bethesda, MD, 7Department of Surgery/Urology, Duke University
Medical Center, Durham, NC, 8Department of Urology/Radiology, Smith Institute for Urology, New York, NY, 9Department
of Urology, University of Southern California, Norris Cancer Center, Los Angeles, CA, USA, 10Department of Urology,
CHU Lille, University Lille, Lille, 11Department of Urology, Institut Paoli-Calmettes Cancer Center, Marseille, France,
12
Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands, and
13
Department of Urology, Medical University of Vienna, Vienna, Austria
Objective
To define the role of multiparametric MRI (mpMRI) for
treatment planning, guidance and follow-up in focal therapy
for prostate cancer based on a multidisciplinary Delphi
consensus project.
Materials and Methods
mpMRI of the prostate. Standardization of imaging protocols
is essential and mpMRIs should be read by an experienced
radiologist. In the follow-up after focal therapy, mpMRI
should be performed after 6 months, followed by a yearly
mpMRI. mpMRI findings should be confirmed by targeted
biopsies before re-treatment.
An online consensus process based on a questionnaire was
circulated according to the Delphi method.
No consensus was reached on whether mpMRI could replace
transperineal template saturation biopsies to exclude
significant lesions outside the target lesion.
Discussion points were identified by literature research and were
sent to the panel via an online questionnaire in three rounds.
Conclusions
A face-to-face consensus meeting followed the three rounds
of questions that were sent to a 48-participant expert panel
consisting of urologists, radiologists and engineers.
Participants were presented with the results of the previous
rounds.
Conclusions formulated from the results of the questionnaire
were discussed in the final face-to-face meeting.
Consensus was reached on a number of areas related to the
conduct, interpretation and reporting of mpMRI for use in
treatment planning, guidance and follow-up of focal therapy
for prostate cancer.
Future studies, comparing mpMRI with transperineal
saturation mapping biopsies, will confirm the importance of
mpMRI for a variety of purposes in focal therapy for prostate
cancer.
Results
Consensus was reached in 41% of all key items.
Keywords
Patients selected for focal therapy should have biopsy-proven
prostate cancer. Biopsies should ideally be performed after
prostate cancer, focal therapy, multiparametric MRI,
consensus
BJU Int 2014; 114: 698–707
wileyonlinelibrary.com
© 2013 The Authors
BJU International © 2013 BJU International | doi:10.1111/bju.12548
Published by John Wiley & Sons Ltd. www.bjui.org
Multiparametric MRI in focal therapy for prostate cancer
Introduction
Two decades ago, imaging of breast tumours had significant
limitations and was unreliable for organ-preserving surgical
treatments. Scoring protocols for breast x-ray imaging and, at
a later stage, breast MRI were developed through formal
attempts to establish agreement among experts on areas of
uncertainty [1–3]. These attempts resulted in reduced
interobserver variability and improved the positive predictive
value of pathology from breast biopsy, which paved the way
for lumpectomy (focal therapy of the breast). Nowadays, this is
the most prevalent treatment for breast cancer, with an
oncological survival rate similar to that obtained with radical
treatment [4].
We are currently witnessing a similar development in prostate
cancer care. Localized prostate cancer is traditionally managed by
radical treatment of the complete organ or by active monitoring.
The first option may result in undesirable side effects such as
erectile dysfunction and urinary incontinence, whereas active
surveillance may cause anxiety about tumour progression and
under-treatment [5]. Improved imaging techniques and biopsy
protocols have led to the early detection of small tumours,
characterized by small cancer volume and low grade [6].
Concerns regarding over-treatment of these small tumours have
introduced the concept of focal therapy, using a variety of
selective ablation technologies. Focal therapy is defined as a
treatment that aims to eradicate known cancer within the prostate
and preserve uninvolved healthy prostatic tissue, and
consequently genitourinary function, without compromising
cancer control [7]. Currently, focal therapy techniques in prostate
cancer include cryotherapy [8], high-intensity focused
ultrasonography [9], laser ablation therapy [10], radiofrequency
ablation [11], irreversible electroporation [12] and photodynamic
therapy [13]. For these forms of treatment, the accurate
identification, localization, demarcation and, ideally, grading of a
lesion are essential. MRI has the potential to fulfill these basic
requirements for focal therapy in prostate cancer, but until
recently, the diagnostic performance of MRI was too low to
implement the technology into the diagnostic evaluation leading
to focal therapy; however, there is increasing evidence, coming
from centres of excellence, to support an accurate diagnostic
performance of MRI, provided that multiple sequences
are used and that their outputs are combined in a so-called
multiparametric MRI (mpMRI) [14]. These sequences
include T1-weighted and T2-weighted imaging, dynamic
contrast-enhanced (DCE) imaging, diffusion-weighted imaging
(DWI) and magnetic resonance spectroscopic imaging (MRSI).
Disagreement among experts in the field of uro-radiology about
the conduct, interpretation, and reporting of mpMRI prohibited
the reproduction of results and the formation of uniformly
comparable literature on diagnostic accuracy and, hence, the
formation of standardized guidelines [15]. Consensus projects
were therefore initiated to reach consensus on recommendations
for standardization of conduct, interpretation and reporting of
prostate mpMRI for prostate cancer detection and localization
[16–18]. These studies and their recommendations aimed to
address the lack of guidelines and consensus by increasing
the uniformity and diagnostic accuracy of mpMRI in prostate
cancer.
Imaging criteria in focal therapy for prostate cancer differ
from the regular criteria in prostate cancer because the
histological diagnosis has usually already been established, and
imaging is therefore used to identify cancers amenable for
focal therapy. The main diagnostic objective of mpMRI is the
identification of the precise location of the tumour within the
prostate and any other cancerous lesions other than the
targeted tumour and, in particular, other high grade lesions. As
the majority of the patients who undergo MRI have had a
previous biopsy, biopsy artifacts are also an important issue.
The other applications of mpMRI in focal therapy are the
monitoring of the treatment itself, and follow-up to document
treatment efficacy. The present paper reports the
recommendations of a panel of experts who participated in a
formal consensus process that was conducted according to the
Delphi method. The consensus project aimed to define when
prostate mpMRI should be applied and how it should be
conducted and reported when used in focal therapy for
prostate cancer.
Materials and Methods
Delphi Method
The essence of the Delphi consensus method is to derive
quantitative estimates through the qualitative assessment of
evidence. Studies of widely different design and quality can be
assessed. When published information is scarce, experts can
make inferences using other data from similar contexts.
Experts’ estimates are aggregated and fed back anonymously
to all participants, who then review their initial responses in
view of group-wide choices. This practice confers anonymity
and allows opinions to be expressed free from peer group
pressure. The Delphi consensus method was considered to be
the most appropriate for our objectives. The method is most
suited to topic areas when there is limited quality evidence to
enable a ‘gold standard’ recommendation to be made. The
Delphi method used for the present study included a series
of three online surveys, in which panelists were presented
with the results of the previous survey and in which the
participants could add, modify, or delete questions for the next
round. A face-to-face discussion panel followed this series of
questionnaires. The Delphi method was applied in accordance
with the reported literature [19–21].
Panel Selection
On the basis of a systematic literature review on [Prostate
Cancer] AND [Focal Therapy] AND [Multiparametric MRI]
© 2013 The Authors
BJU International © 2013 BJU International
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Muller et al.
Table 1 Delphi panel.
Selected participants
Profession
Location
1 Hashim Ahmed
2 Jelle Barentsz
3 Maurizio Brausi
4 Peter Carroll
5 Jean-Yves Chapelon
6 Peter Choyke
7 François Cornud
8 Sébastien Crouzet
9 Theo de Reijke
10 Bob Djavan
11 Scott Eggener
12 Mark Emberton
13 Marc Engelbrecht
14 Jurgen Fütterer
15 Albert Gelet
16 Paolo Gontero
17 Rajan Gupta
18 Masoom Haider
19 Mukesh Harisinghani
20 Stijn Heijmink
21 Hedvig Hricak
22 Didier Jacqmin
23 J. Stephen Jones
24 Aaron Katz
25 Kirkham
26 Laurence Klotz
27 John Kurhanewicz
28 Nathan Lawrentschuk
29 Constantino Leonardo
30 Uri Lindner
31 Vibeke Løgager
32 Michael Marberger
33 Alessandro Napoli
34 David Penson
35 Peter Pinto
36 Thomas Polascik
37 Ardeshir Rastinehad
38 Jean de la Rosette
39 Olivier Rouvière
40 Georg Salomon
41 Peter Scardino
42 MichielSedelaar
43 Samir Taneja
44 Joachim Thüroff
45 Osamu Ukimura
46 SadnaVerma
47 Arnauld Villers
48 Jochen Walz
Urologist
Radiologist
Urologist
Urologist
Engineer
Radiologist
Radiologist
Urologist
Urologist
Urologist
Urologist
Urologist
Radiologist
Radiologist
Urologist
Urologist
Radiologist
Radiologist
Radiologist
Radiologist
Radiologist
Urologist
Urologist
Urologist
Radiologist
Urologist
Radiologist
Urologist
Urologist
Urologist
Radiologist
Urologist
Radiologist
Urologist
Urologist
Urologist
Urologist/Radiologist
Urologist
Radiologist
Urologist
Urologist
Urologist
Urologist
Urologist
Urologist
Radiologist
Urologist
Urologist
University College Hospital London, London, UK
Radboud University Hospital, Nijmegen, the Netherlands
EstenseS. Agostino Hospital, Modena, Italy
University of California, San Francisco, USA
National Institute of Health and Medical Research, Paris, France
National Cancer Institute, Bethesda, USA
Cochin Hospital, Paris, France
Edouard Herriot Hospital, Lyon, France
AMC University Hospital, Amsterdam, the Netherlands
New York University, New York, USA/University of Vienna, Vienna, Austria
University of Chicago, Chicago, USA
University College Hospital London, London, UK
AMC University Hospital, Amsterdam, the Netherlands
Radboud University Hospital, Nijmegen, the Netherlands
Edouard Herriot Hospital, Lyon, France
Molinette University Hospital, Torino, Italy
Duke University Medical Center, Durham, USA
Sunnybrook Hospital, Toronto, Canada
Harvard Medical School, Boston, USA
Dutch Cancer Institute, Amsterdam, the Netherlands
Memorial Sloan Kettering Cancer Center, New York, USA
University Hospital of Strasbourg, Strasbourg, France
Cleveland Clinic, Cleveland, USA
Winthrop Urology Hospital, New York, USA
University College Hospital London, London, UK
Sunnybrook Hospital, Toronto, Canada
University of California, San Francisco, USA
University of Melbourne, Melbourne, Australia
University of Rome, Rome, Italy
Princess Margaret Hospital, Toronto, Canada
Copenhagen University, Hospital Herlev, Herlev, Denmark
Medical University of Vienna, Vienna, Austria
Sapienza University of Rome, Rome, Italy
Vanderbilt-Ingram Cancer Center, Nashville, USA
National Cancer Institute, Bethesda, USA
Duke University Medical Center, Durham, USA
Smith Institute for Urology, New York, USA
AMC University Hospital, Amsterdam, the Netherlands
Edouard Herriot Hospital, Lyon, France
University of Hamburg Martini Clinic, Hamburg, Germany
Memorial Sloan Kettering Cancer Center, New York, USA
Radboud University Hospital, Nijmegen, the Netherlands
NYU Langone Medical Center, New York, USA
University Medical Center, Johannes Gutenberg University, Mainz, Germany
Keck Medical Center of USC, Los Angeles, USA
University of Cincinnati, Cincinnati, USA
Lille University Hospital, Lille, France
Institut Paoli-Calmettes, Marseille, France
(and synonyms), experts in the field were selected. All experts
published in the field of focal therapy for prostate cancer
and/or mpMRI were selected by their peers. Fifty experts were
approached, one declined and one retracted after the first
round, resulting in 48 panelists (urologists, radiologists and
engineers) from Europe, North America, Asia and Australia
(Tables 1,2). Commercial bias was excluded through the use of
institutional funds.
Construction of the Questionnaire
An online questionnaire, operated and designed using an
online questionnaire program (http://www.SurveyMonkey
700
© 2013 The Authors
BJU International © 2013 BJU International
.com), containing 41 items was constructed between 28
January and 15 April 2013. This online questionnaire was
presented to the panelists in three rounds between 15 April
and 29 April 2013, each time with a 1-week interval used for
analysis and construction of the subsequent round. Items
discussed can be found in Tables 3–5. B.G.M. and W.v.d.B.
designed the first round of questionnaires, under the
supervision of M.M. and J.d.l.R., using the literature review as
described in item 2.2. Questions were based on controversial
items in the studies, or items on which evidence was lacking.
All subsequent rounds were designed by the feedback from
the participating panelists. Each round was analysed and
graphically presented to the participants in the next round.
Multiparametric MRI in focal therapy for prostate cancer
Table 2 Panel characteristics.
Specialties, %
Urologist
Radiologist
Engineer
Urology-Radiology
Focal therapy experience, %
High-intensity focused ultrasonography
Cryotherapy
Laser therapy
Irreversible electroporation
Photodynamic therapy
Radiofrequency ablation
Other
Patients treated with focal therapy on a yearly basis
Range
Mean estimated number of patients
Total estimated number of patients treated on a yearly basis
by the panel
62.5
33.3
2.1
2.1
59.6
46.8
31.9
12.8
29.8
12.8
12.8
0–300
38.15
1793
Participants were asked to clarify per question whether they
considered themselves sufficiently knowledgeable to answer.
Face-to-Face Meeting Format
The face-to-face meeting took place on 29 May 2013, in
Noordwijk, the Netherlands. Participants from the online
questionnaire were invited to join. Fifteen experts in urology
and uro-radiology attended the meeting and are listed among
the authors of this manuscript. All panel members also
participated in the online series of questionnaires. During the
meeting, the results from the online questionnaire were
discussed in plenary sessions to draw conclusions from the
acquired data. No new input was taken into consideration. A
chairman (B.G.M.), with no financial disclosures to declare,
was chosen to preside over the meeting.
Interpretation of the Results
Consensus on a topic was defined as >80% unanimity on the
question regarding this topic in the online questionnaire. The
participants in the discussion are listed in Table 1.
Results
The results of the questionnaires are shown in Tables 3–5.
During the meeting, final conclusions were formulated based
on the acquired data from the questionnaires. Questionnaire
results were not altered and no new data were taken into
account during the meeting. A summary of the questionnaire
results and items discussed in the meeting is given below.
Consensus was reached on 41% of the items.
Patient Selection and Treatment Planning
The panel agreed that mpMRI is currently the ideal imaging
tool for focal therapy of prostate cancer. For patient selection,
histologically proven prostate cancer is still considered crucial.
In other words, the prostate cancer should be biopsy-proven
before receiving any focal therapy. These biopsies should
preferably be done after mpMRI. The panel reached a
consensus that 3 Tesla is the recommended field strength for
use in focal therapy. An endorectal coil is increasingly
recommended at low field strengths (63.8% for 1.5 Tesla
compared with high field strengths (34% for 3 Tesla). There
was a strong consensus that a pelvic phased array coil was
indispensable in prostate mpMRI. The panelists recommended
the following sequences: T1-weighted, T2-weighted and DCE
imaging, and DWI. The inclusion of MRSI in mpMRI was not
supported by a large group (only 10.6%). The majority of the
panel (68.1%) defined 0.5 mL as the lower limit of a reliable
detection rate in Gleason 6 tumours. In Gleason 7 tumours,
23.4% of the panel defined 0.2 mL as the lower limit for
detection, but still most participants (65.96%) defined 0.5 mL
as the lower limit. On this topic there was a remarkable
difference between urologists and radiologists (6.9 vs 50%,
respectively, defined the lower limit as 0.2 mL). The panel
strongly agreed that tumour location within the prostate
influenced the diagnostic accuracy of mpMRI. The detection
rate is most accurate for tumours in the peripheral zone.
The detection rate of tumours on mpMRI seemed to be
independent of prostate volume. There was a strong consensus
that ideally, the MRI should be performed before prostate
biopsies. If this was not possible, a post-biopsy interval period
of 6–8 weeks should be considered to facilitate reliable images
on mpMRI. No consensus could be reached on the question of
whether mpMRI was an adequate alternative for transperineal
template saturation biopsies for the exclusion of significant
lesions outside the target lesion. A study comparing the
diagnostic performance of mpMRI to template saturation
biopsies should first be executed, with sufficient power to
adequately demonstrate the ability of mpMRI to replace the
role of template saturation mapping biopsies.
Treatment Guidance
Most panel members use TRUS as guidance for focal therapy.
Of all panel members, 35.7% use MRI-guided focal therapy.
Consensus was reached that, where real-time MRI monitoring
of focal therapy is used, magnetic resonance thermometry is
the best suitable technology (restricted to thermal ablation
technologies). The panel stated that the standardization of
conduct and reporting protocols was of paramount
importance (100% consensus), but 40.5% of the panel
members worked with a self-developed protocol, and 7.1% did
not even use a standardized protocol for MRI reporting. This
illustrates that standardization between centres is essential.
Finally, the need for a specialized radiologist to report on
prostate mpMRI was debated. All of the panel members
agreed that a specialized radiologist was necessary for image
acquisition, reading and reporting of prostate mpMRI. To
become expert and to remain experienced, the radiologist
© 2013 The Authors
BJU International © 2013 BJU International
701
Muller et al.
Table 3 Results regarding treatment planning.
Which diagnostic tool do you recommend for focal therapy treatment planning?
MRI
mpMRI
TRUS
Histoscanning
Three-dimensional plotting
Transperineal saturation biopsies
Other
With mpMRI. which field strength do you recommend for use in focal prostate cancer treatment planning?
3 Tesla
1.5 Tesla
There is no significant difference between the two
I don’t know
Do you recommend the use of an endorectal coil in prostate mpMRI at 1.5 Tesla?
Yes
No
I don’t know
Do you recommend the use of an endorectal coil in prostate mpMRI at 3.0 Tesla?
Yes
No
I don’t know
Is an endorectal coil indicated if the mpMRI is used for diagnosis of prostate cancer?
Yes
No
I don’t know
Is an endorectal coil indicated if the mpMRI is used for localization of small lesions for focal therapy treatment planning?
Yes
No
I don’t know
Are there any exclusion criteria for use of an endorectal coil in prostate mpMRI? (Multiple options possible)
No, endorectal coil is always indicated
In patients who are eligible for radiation therapy (since it deforms the prostate)
When localizing small tumours for focal treatment targeting (since it deforms the prostate)
In patients on active surveillance
When patients can not tolerate the endorectal coil (haemorrhoids, colorectal surgery)
Other
I don’t know
Is the use of a pelvic phased array coil indicated for prostate mpMRI. in focal therapy treatment planning (localizing small
lesions)
Yes, always (with or without endorectal coil)
Yes, and always without an endorectal coil
Yes, and always in combination with an endorectal coil
No, never
I don’t know
Which mpMRI sequences do you recommend for prostate MRI?
T1-weighted imaging
T2-weighted imaging
DCE
DWI
MRSI
I don’t know
In Gleason 6 tumours, what are the lower limits of detection on mpMRI, with respect to tumour size?
0.2 mL
0.5 mL
0.7 mL
1.0 mL
1.2 mL
I don’t know
In Gleason 7 tumours, what are the lower limits of detection on mpMRI, with respect to tumour size?
0.2 mL
0.5 mL
0.7 mL
1.0 mL
1.2 mL
I don’t know
702
© 2013 The Authors
BJU International © 2013 BJU International
Overall,
%
Radiologists,
%
Urologists,
%
26.1
80.4
23.9
0
6.5
19.6
15.2
35.71
92.86
14
0
0
7.14
0
23.3
73.3
30
0
10
26.7
16.7
80.9
4.3
12.8
2.1
81.25
0
18.75
0
79.31
6.9
10.34
3.45
63.8
29.8
6.4
87.5
12.5
0
48.28
41.38
10.34
34
59.6
6.4
31.25
62.5
6.25
34.48
58.62
6.9
42.6
55.3
2.1
62.5
37.50
0
31.03
65.52
3.45
51.1
46.8
2.1
75
25
0
37.93
58.62
3.45
12.8
27.7
17
23.4
23.4
12.8
8.5
12.5
37.5
18.75
31.25
68.75
18.75
0
13.79
20.69
17.24
20.69
51.72
10.34
13.79
72.3
14.9
6.4
0
6.4
75
12.5
12.5
0
0
68.79
17.24
3.45
0
10.34
85.1
93.6
85.1
90
10.6
2
93.75
100
81.25
100
18.75
0
79.31
89.66
86.21
83.33
6.9
3.4
8.5
68.1
4.3
8.5
2.1
8.5
6.25
75
0
6.25
6.25
6.25
6.9
69
6.9
10.3
0
6.9
23.4
66
2.1
4.3
0
4.3
50
50
0
0
0
0
6.9
75.9
3.4
6.9
0
6.9
Multiparametric MRI in focal therapy for prostate cancer
Table 3 Continued.
Does tumour location within the prostate influence the accuracy of prostate MRI?
Yes
No
I don’t know
Is the detection rate of prostate tumours on mpMRI dependent on prostate volume? (Multiple answers possible)
No
Yes, with increasing prostate size detection rate decreases
Yes, with large amount of BPH, false positive rate increases
I don’t know
Is there a minimal time span between prostate biopsies and MRI to facilitate reliable images?
Yes, 3 weeks
Yes, 6 weeks
Yes, 8 weeks
Yes, 12 weeks
Do you consider mpMRI of the prostate an adequate alternative to systematic template saturation biopsies in patient
selection for focal therapy?
Yes
No
I don’t know
Do you consider prostate mpMRI at least as adequate as template saturation biopsies in patient selection for focal therapy?
Yes, always
Yes, but only in patients with Gleason 7 tumours, or higher
Yes, but only if targeted biopsy confirms the diagnosis
No, never
If tumour location within the prostate influences the accuracy of mpMRI, then the detection rates for tumours are lowest,
highest or intermediate in:
the transition zone
the peripheral gland
the anterior gland
should read at least 50 prostate mpMRI scans with
pathological feedback per year.
Treatment Follow-Up
It was found that mpMRI was the preferred method of focal
therapy follow-up (95.7% consensus). Furthermore, the
majority of the panel supported the use of PSA, prostate
biopsies and MRI-TRUS-guided biopsies in the follow-up of
focal therapies for prostate cancer. Of the panel members
76.6% indicated that mpMRI could accurately identify tumour
recurrence in the prostate. Regarding the follow-up schedule
of mpMRI after focal therapy, no consensus was reached;
nonetheless, 63.83% indicated that the first mpMRI should be
performed 6 months after focal treatment. The performance of
a baseline mpMRI immediately or 3 months after treatment
was discussed, but this did not receive much support (17.0%).
Equal support for both mpMRI every 6 months (51.1%) and
every year (42.6%) was found for imaging intervals after initial
imaging after focal therapy. In the face-to-face meeting, the
panel agreed that mpMRI every year after treatment was
sufficient. There was a strong agreement (89.4%) that
definitive tissue destruction immediately after focal therapy
results in a loss of enhancement on a DCE MRI. Furthermore,
67.4% of the panelists defined definitive tissue destruction as a
loss of enhancement on DCE MRI, 6 months after treatment.
Overall,
%
Radiologists,
%
Urologists,
%
95.2
4.8
0
92.86
7.14
0
96.2
3.8
0
63.8
29.8
12.8
2.1
62.5
37.5
18.75
6.25
69
24.1
10.3
6.9
4.3
66
19.1
10.6
12.5
56.25
12.5
18.75
0
69
24.1
6.9
54.3
39.1
6.5
57.14
21.43
21.43
40
53.3
6.7
23.4
8.5
46.8
21.3
Lowest
%
46.2
0
20.5
18.75
18.75
50
12.5
Intermediate,
%
35.9
4.8
59.0
27.6
3.4
41.4
27.6
Highest,
2.6
88.1
10.3
Moreover, 6 months after treatment, scarring might be
observed on T2-weighted images (19.6%). There was a strong
consensus that mpMRI findings could be an indication for
biopsies in the follow-up of focal therapy. Targeted biopsy was
the best strategy to perform biopsies and 70% of panelists
indicated that TRUS-MRI fusion was the best way to guide the
targeted biopsies in the follow-up of focal therapy.
Recommendations of the Panel
• mpMRI was the recommended diagnostic tool for treatment
planning in focal therapy for prostate cancer. The panel
stated that ideally, this mpMRI should be made on a 3-Tesla
device. When a 1.5-Tesla device was the only device
available, an endorectal coil was deemed to be essential. A
minimum of the following sequences should be included:
T1-weighted, T2-weighted and DCE imaging and DWI. The
location of the tumour within the prostate could influence
the accuracy of the mpMRI, which the clinician should keep
in mind.
• Magnetic resonance thermometry was regarded as a possible
technology for real-time monitoring of thermal ablation.
The panel preferred this technology. TRUS-MRI fusion
was recommended by the panel for targeting biopsies.
Standardized protocols for the acquisition and reporting of
mpMRIs were considered of paramount importance and
© 2013 The Authors
BJU International © 2013 BJU International
703
Muller et al.
Table 4 Results regarding treatment guidance.
Which imaging technique is used in your hospital for focal therapy guidance, during treatment?
TRUS
MRI
MRI-TRUS fusion
We don’t do focal therapy
Is there a MRI technique suitable for real-time focal treatment monitoring?
Yes
No
I don’t know
If there is a possibility for real-time magnetic resonance focal treatment monitoring, which one do you prefer?
Magnetic resonance thermometry
TRUS-MRI fusion
No preference
I do not believe that there is a MRI technique suitable for real-time monitoring
Do you recommend the use of TRUS-MRI fusion for use in focal therapy for prostate carcinoma? (Multiple
answers possible)
Yes, TRUS-MRI fusion for treatment planning
Yes, TRUS-MRI fusion for real-time treatment guidance
Yes, TRUS-MRI fusion for targeted biopsy
No
What is your opinion about deformation artifacts in TRUS-MRI fusion?
Existent, but always acceptable
Only acceptable when data are elastically fused (software correction for tissue deformation)
Only acceptable for lesions in the peripheral zone
Not acceptable
I don’t know
Do you think it is important that standardized protocols are used for reporting of prostate MRIs?
Yes
No
Do you use a standardized acquisition/reporting protocol for prostate mpMRIs in your hospital?
Yes, ESUR/PI-RADS Guidelines
Yes, Likert Score
Yes, self developed protocol
No
I don’t know
Do you consider it important that all prostate mpMRIs are made and reported by a specialized radiologist?
Yes
No
How many prostate mpMRIs should a radiologist report on a yearly basis to remain experienced?
>30
>50
>75
>100
I don’t know
Overall, %
Radiologists, %
Urologists, %
59.5
35.7
26.2
7.1
35.71
50
14.29
14.29
66.7
36.7
23.3
0
89.4
6.4
4.3
93.75
0
6.25
86.2
10.3
3.4
85.1
12.8
4.3
4.3
87.5
12.5
6.25
0
82.8
10.3
3.4
6.9
42.6
40.4
85.1
10.6
43.75
31.25
87.5
6.25
41.4
44.8
82.8
13.8
8.5
72.3
2.1
2.1
17
12.5
75
0
0
18.75
3.4
72.4
3.4
3.4
17.2
100
0
34
4.8
40.5
7.1
11.9
100
0
0
55.3
12.8
27.7
4.3
100
0
42.68
7.14
50
0
0
100
0
0
56.25
25
18.75
0
100
0
30.77
3.8
34.6
11.5
19.2
100
0
0
55.2
6.9
31
6.9
ESUR/PI-RADS, European Society of Urogenital Radiology/Prostate Imaging – Reporting and Data System.
should be used. Furthermore, a specialized and experienced
radiologist should report all mpMRI results.
• mpMRI was concluded to be the best suitable technology
for follow-up after focal therapy and should therefore be
used in the follow-up schedule of focal therapy. Immediately
after treatment, a successful ablation was defined as a loss of
enhancement in the DCE sequence. Targeted biopsies
should be carried out if follow-up MRI indicated suspected
recurrent/residual tumour.
• No consensus could be reached on the topic of template
saturation biopsies for patient selection. Forty-six percent of
the panel stated that mpMRI was not yet an adequate
alternative for template saturation biopsies.
704
© 2013 The Authors
BJU International © 2013 BJU International
Discussion
The use of the Delphi method produced consensus in 41% of
the key items (14 out of 34). On some questions there was a
considerable difference in opinions between radiologists and
urologists (Tables 2–4). Although the panel reached a
consensus for 3 Tesla as the ideal field strength in prostate
mpMRI, some panelists mentioned that 1.5 Tesla might have
the same diagnostic accuracy. This is supported by a recent
publication by Bratan et al. [22]. The panel agreed that, with
increasing Gleason score, smaller tumours could be detected
on mpMRI. Substantiation of this topic was provided in
studies by Bratan et al. [22] and Turkbey et al. [23]. As a tool
for the real-time guidance of thermal focal therapy, magnetic
Multiparametric MRI in focal therapy for prostate cancer
Table 5 Results regarding treatment follow-up.
Which technique(s) do you recommend for focal therapy follow-up? (Multiple options are possible)
mpMRI
TRUS
Prostate biopsies
MRI-TRUS fusion
Contrast enhanced ultrasonography
PSA
DRE
Is mpMRI a reliable tool for follow-up after focal therapy for prostate carcinoma?
Yes
No
I don’t know
After focal therapy of prostate cancer, when should the first follow-up mpMRI be done?
0–7 days after treatment (baseline)
3 months after treatment
6 months after treatment
1 years after treatment
I don’t know
At which intervals should mpMRI be performed in the follow-up of focal therapy of prostate cancer?
mpMRI every 6 months
mpMRI every year
no routine mpMRI, only based on clinical indications
Immediately after treatment, how does definitive tissue destruction present on a prostate mpMRI? (Multiple
answers possible)
Low signal on T2-weighted images (scar)
Loss of enhancement on DCE-MRI
ADC above a certain threshold (dependent on b-value of the scanner)
Increased choline/citrate ratio on MRSI
Other
I don’t know
6 months after treatment, how does definitive tissue destruction present on a prostate mpMRI? (Multiple answers
possible)
Low signal on T2-weighted images (scar)
Loss of enhancement on DCE-MRI
ADC above a certain threshold (dependent on b-value of the scanner)
Increased choline/citrate ratio on MRSI
Other
I don’t know
Which is the best biopsy strategy for follow-up biopsies after focal therapy?
Systematic biopsies
Targeted biopsies
Template saturation biopsies
How should biopsies in the follow-up of focal therapy be guided?
TRUS-guided based on mpMRI images
MRI-guided
Either TRUS- or MRI-guided
TRUS-MRI fusion-guided
Overall, %
Radiologists, %
Urologists, %
95.7
8.5
48.9
31.9
8.5
51.1
19.1
100
0
31.25
18.75
0
43.75
12.75
93.1
13.8
58.6
34.5
10.3
55.2
24.1
76.6
17
6.4
81.25
12.5
6.25
72.4
20.7
6.9
17
14.9
63.8
2.1
2.1
12.5
12.5
68.75
0
6.25
17.2
17.2
62.1
3.4
0
51.1
42.6
6.4
68.75
25
6.25
37.9
55.2
6.9
10.6
89.4
4.3
0
4.3
6.4
18.75
100
6.25
6.25
6.25
6.9
82.8
0
0
3.4
6.9
19.6
67.4
2.20
0
6.5
4.3
18.75
68.75
0
0
6.25
6.25
21.4
64.3
3.6
0
7.1
3.6
15.2
82.6
2.2
6.25
93.75
0
21.4
75
3.6
17
4.3
8.5
70.2
18.75
6.25
12.5
62.5
17.2
3.4
6.9
72.4
ADC, apparent diffusion coefficient.
resonance thermometry is a suitable technology. Although not
widely implemented, magnetic resonance thermometry results
seem promising for future application [24]. Furthermore, the
panel agreed that TRUS-MRI fusion is a promising technology
for targeted biopsies of the prostate. Deformation errors
can arise, but these are minimal and therefore acceptable.
TRUS-MRI-fusion-guided biopsies have shown similar results
to those of MRI-guided biopsies [25]. In the follow-up section,
the panel agreed that PSA should be part of the follow-up
after focal therapy, but the literature has not yet determined,
nor has a consensus been reached on, how to interpret PSA
kinetics after focal therapy.
Face-to-face consensus methods or expert group discussions
are prone to biases. Dominant personalities are known to be
capable of influencing the opinion of the group to a significant
extent [26]. The Delphi method is very well suited to reduce
this type of bias. All panelists were given the opportunity to
actively contribute and share their opinions anonymously.
During the face-to-face meeting, conclusions were only
formulated from the anonymously acquired data; no new
input was given. The Delphi method also implies that the
group is presented with questions, which are formulated based
upon the latest literature, resulting in a high level of validity.
Based on their knowledge, the panelists were given the
© 2013 The Authors
BJU International © 2013 BJU International
705
Muller et al.
opportunity to add discussion points, questions and
amendments to the series of questions, to achieve consensus
about what is important in the view of the group as a whole.
Because panelists from Europe, North America, Asia and
Australia were participating in the panel, all topics were
viewed within this broad perspective. The panel reached a
consensus at a unanimity level of ∼80%. This may be
considered a limitation, since experts were selected on the
basis of their expertise in prostate cancer.
For focal therapy of prostate cancer, state-of-the-art imaging is
of utmost importance. The physician should be able to target
the tumour and has to ensure that, outside the targeted area,
no other significant tumour is missed. Through incorporation
of the recommendations reported in the present paper, the
conduct, interpretation and reporting of mpMRI in treatment
planning, treatment guidance and treatment follow-up of focal
therapy will be more consistent and standardized. With pooled
analyses, the clinical diagnostic accuracy of mpMRI will
increase. The panel concluded that mpMRI for treatment
planning should ideally be carried out before biopsy; however,
limitations such as costs, lack of availability of MRI, lack of
standardization and reproducibility, mean that this approach
cannot always be applied in daily practice. Previous studies
have also recommended such an approach [27]. Imaging
criteria for mpMRI are stricter in tissue-preserving strategies
such as active surveillance and focal therapy. For focal therapy,
it is not only important to be able to see the target lesion, but
also to exclude significant tumours elsewhere in the prostate.
If the accuracy of mpMRI is great enough to exclude
significant tumour sufficiently, template saturation mapping
biopsies in patients undergoing focal therapy can potentially
be avoided in the future.
Additionally, the detection and localization components of
mpMRI could assist in targeting biopsies. A large metaanalysis recently published by Nelson et al. [28] showed that
MRI-guided biopsies potentially have a detection rate
equivalent to transperineal template saturation biopsies;
however, these findings are yet to be validated in prospective
studies. TRUS-mpMRI fusion can fulfill a significant role in
this respect and was also recommended by the panel. It is
important to note that most of the literature is generated in
high-volume expert centres. Consequently, panel members
were also from these centres. It might therefore be challenging
to extrapolate these results to settings outside of these expert
centres.
The relatively low amount of consensus (41% of the topics)
indicates that there are many uncertainties in the field. The
results of the consensus project are, therefore, not immediately
to be used as guidelines for clinical practice. Nevertheless,
given the numerous studies that have been performed in this
area of research, we anticipate that these consensus statements
will be meaningful and that other research groups will
706
© 2013 The Authors
BJU International © 2013 BJU International
implement the recommendations in new study protocols on
focal therapy and imaging. Dickinson et al. [16] already
pointed out in 2011 that transperineal saturation biopsies are
the optimum reference standard for studies on the diagnostic
accuracy of mpMRI, because they overcome random and
systematic sampling errors by sampling the gland every 5 mm,
provide three-dimensional coordinates for correlation to
imaging and can be applied to all men.
It is anticipated that future studies, comparing mpMRI with
transperineal saturation mapping biopsies, will confirm the
important role of mpMRI in a variety of purposes in focal
therapy for prostate cancer.
In conclusion, focal therapy is an emerging technique for
prostate cancer treatment. For this treatment optimum
imaging is paramount and mpMRI has the potential to meet
these strict imaging requirements. Through a structured
consensus method, our panel agreed on several key issues
regarding mpMRI for use in focal therapy. Before these
recommendations can be implemented in clinical protocols,
they first have to be validated in prospective clinical trials.
Acknowledgements
B.G.M. and W.v.d.B. received an unrestricted research grant
from the Cure for Cancer Foundation.
Conflict of Interest
A.R. received non-financial research support from Philips
during the study period. J.d.l.R. reports grants and personal
fees from Angiodynamics during the conduct of the study.
U.U. is an advisory board member at SonaCare Medical LLC.
A.V. was a consultant at Janssen Pharmaceutica, Astellas and
Ferring during the study period. Furthermore, he received
research grants from Ipsen and Takeda.
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Correspondence: Berrend Muller, Academic Medical Center,
Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
e-mail: [email protected]
Abbreviations: mpMRI, multiparametric MRI; DCE, dynamic
contrast-enhanced; DWI, diffusion-weighted imaging; MRSI,
magnetic resonance spectroscopic imaging.
© 2013 The Authors
BJU International © 2013 BJU International
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