Download - UBC Urology Rounds

Prostate MRI in Practice
Experience at Two Canadian Centers
Masoom A. Haider, MD
Professor of Radiology
University of Toronto, Canada
Head of Abdominal MRI
University Health Network & Mount Sinai
Hospital
Pre-MRI Status
•  Wide variation in biopsy practice
–  Number of cores
–  Core locations
–  Frequency
–  Who performs the biopsy
•  Wide variation in therapeutic options
•  Role of radiology limited to advanced
disease
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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PSA Screening NEJM
•  “48 additional cases of prostate cancer
would need to be treated to prevent one
death from prostate cancer”
Schroder FH et al. Screening and Prostate-Cancer Mortality in a
Randomized European Study. N Engl J Med 2009;360:1320-8.
•  After 7 to 10 years of follow-up, the rate
of death from prostate cancer was very
low and did not differ significantly
between the two study groups
Andriole GL et al. Mortality Results from a Randomized Prostate-Cancer
Screening Trial. N Engl J Med 2009;360:1310-9.
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
We Need Better Prognostication
•  Up to 70% of men with elevated PSA
will not have a cancer found (Hiding?)
•  There is a high prevalence of
insignificant cancer with a 27-56% overdetection rate (Will it kill me?)
•  We cannot predict for an individual
patient with “low risk” disease whether
or not the cancer will kill them in the
long run
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
2
Prostatectomy for Everyone?
Therapeutic Morbidity 5 years
• 
• 
• 
• 
Urinary dysfunction at 5 years 3-29%
Bowel 4-29%
Sexual Dysfunction 42-77%
Quality of life
Potosky et al JNCI 2004, 96:18
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Current TRUS Bx
10 or more cores
•  Gleason score is the single best
independent prognostic factor
•  15%-34% of cancers are undergraded
with 10 or more cores on random biopsy
•  2.5% complication rate requiring
hospital admission
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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“Game Changers”
1.  Better prognostic marker of lethal
disease than PSA
Only treat when required
2.  Better localization of the most
significant cancer
Only biopsy & treat where required
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
MRI Techniques
Multispectral Approach
T2 weighted imaging
+
Diffusion weighted (ADC)
DCE MRI
Proton spectroscopy
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Turkbey et al, Radiology: Volume 255: Number 1—April 2010
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Prostate Cancer
Detection
Significant
Cancer
Normal
15% cancer
Surgery
or Rads
Minimally
Invasive
LOW
MORBIDITY
Insignificant
Cancer
Active
Surveillance
>4
PSA
TRUS Bx
MRI
HGPIN/ASAP
Normal
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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DCE MRI
Temporal resolution should
be <10s and preferably <5s
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Methods
DCE MRI of Cancer
3 min
Relative SI vs Tim e
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0
100
200
300
400
500
s
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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erMRI for Localization
n=34
T2
MRS
DCEMRI
Sensitivity
52-67
77-80
84-85
Specificity
73-74
84-87
83-88
PPV
38-43
64-68
61-70
NPV
83-88
91-93
94-95
Accuracy
69-71
82-85
83-87
Tumors >0.5cc
JJ Futterer Radiology 241-2:449-458
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
n=49
Peripheral Zone
T2
T2+DWI
Sensitivity
73/127 (58)
111/127 (87)
Specificity
152/167 (91)
134/167 (80)
PPV
73/88 (83)
111/144 (77)
NPV
152/206 (74)
134/150 (89)
Accuracy
225/294 (77)
245/294 (83)
Haider, van der Kwast, Evans, Trachtenberg et a, 2007l
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Parameter
T2
DCE
DWI
AUC
0.75
0.79
0.85
Tan et al AJR:199:October 2012 – Metaanalysis 19 publications
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
ADC
Correlates with Gleason Grade
Az =0.9 >G6
Hambrock T et al. Radiology 2011
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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MRI Techniques
Multispectral Approach
T2 weighted imaging
+
Diffusion weighted (ADC)
DCE MRI
Proton spectroscopy
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Gleason 3+4
18% of core
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Knowledge of Pathology
(Radical Prostatectomy)
•  Prostate cancer is multifocal in 80%
•  Average number of cancers/patient is 2.2
•  There is usually a dominant focus
–  Mean index tumor volume 2.4cc while second
largest is 4x smaller 0.6cc
•  Extraprostatic extension is usually from the
dominant focus
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
What do we want to find?
•  Not all cancers need to be found
•  Recent genetic studies suggest
metastases arise from a single focus
•  Controversial
–  There is general consensus that any tumor
of G4+3 or higher should not be missed
–  There is general consensus that G3+3
tumors <0.5cc (1cm diameter) are not of
significance
–  High volume GS 6 and low volume GS
3+4?
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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T2-weighted image
ADC map (mm2/s)
2.4
2.0
1.6
1.2
T2 quantitative map (ms)
kep map (min-1) - Brix
14
200
10
150
6
100
50
2
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Sensitivity/Specificity Grade/Size
Conservative
•  Gl 7+ <0.5cc
•  Gl 7+ ≥ 0.5-1.3cc
•  Gl 7+ > 1.3cc
70%
80%
90%
80%
85%
>90%
Villers, at al - 2006
Puech/Villers, et al - 2009
Turkbey, et al - 2010 (Radiology)
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Anterior Tumors
(Base/Apex)
30%
70%
Copyright ©Radiological Society of North America, 2007
Choi, Y. J. et al. Radiographics 2007;27:63-75
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Oto A et al. Radiology 2010;257:715-723
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Oto A et al. Radiology 2010;257:715-723
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Central Gland Tumors
PSA >10ng/ml
30% of tumors involve the central gland
central zone + transition zone + periurethral glands
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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T2#
ADC#
DCE#MRI#–#kep#map#
G3+4 70% core
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Patient Experience
•  Empty bladder
•  No sexual activity 48/72 hours
•  Empty rectum
–  Laxative/bowel prep
–  NPO
•  Endorectal device
•  Exam time 30-45 min
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Endorectal Coil?
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Post biopsy hemorrhage should
be avoided for localization
Wait as long as possible from last
biopsy
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Interpretation
•  Scoring Scheme (1-5)
•  Hierarchical interpretation
–  T2+DWI gives first score
–  DCE can further increase score
•  Zone specific interpretation
–  PZ vs Central gland
•  I never interpret without prior biopsy
information and PSA
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Reporting
Divide prostate into
regions that match the
biopsy extended biopsy
scheme used by or
urologists (16)
Use the lowest ADC
region to define
suspicion for high grade
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
IMPRESSION:
Definite large anterior cancer occupying
the anterior mid gland and extending to
the anterior apex. Findings are
suspicious for high grade disease
(Gleason score 7 or higher). No definite
extraprostatic extension. Sensitivity of
MRI for extraprostatic extension is 60%.
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Improvement in Biopsy Yields
•  n=68, 2 or more prior neg TRUS Bx
•  59% (40/68) tumor detection rate vers
15% for TRUS Bx alone
–  directed cores, 2-7 (median 4)
–  Target PPV 40% (46/114)
•  37/40 had clinically significant disease
•  Time 14-75 minutes
Hambrock et al, J of Urol, Feb 2010
• 
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Hambrock et al, J of Urol, Feb 2010
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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History
Entry onto active surveillance
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Transverse(
2012-10-31
Sagittal(
41
Medical Imaging – Princess Margaret Hospital – University Health
Network
– Mount Sinai Hospital – University of Toronto
Eigen
Confidential
3D(TRUS(Volume(Registered(to(MRI(
2012-10-31
42
Medical Imaging – Princess Margaret Hospital – University Health
Network
– Mount Sinai Hospital – University of Toronto
Eigen
Confidential
21
MR9TRUS(Fusion(Biopsy(
Planned(Target((red)(and(Sampled(Cores(blue)(
2012-10-31
43
Medical Imaging – Princess Margaret Hospital – University Health
Network
– Mount Sinai Hospital – University of Toronto
Eigen
Confidential
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Pathology
Gleason 6 (3+3) 40% core
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
High PSA Prior Negative Biopsy
•  56yo male
•  PSA 6.87ng/ml
•  Protocol
–  3T, no endorectal coil, T2, DWI, DCE
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Active Surveillance with MRI/US
Fused Biopsy
• 
• 
• 
• 
SAMPLING
>30 patients on AS
Mean cores 2 vs 12
~20% had actionable tumors missed on
12 core
•  0% actionable tumors missed on fused
biopsy
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Staging
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
T2 – Big Peripheral Zone
Cancers (20 years ago)
Extracapsular Tumor
Seminal Vesicle Invasion T3b
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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G4+3, 64yo PSA 7.63 DRE neg
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Gleason 9
DRE +, PSA 4.5
Radiation
pT3a
DRE -, PSA 3.7
Nerve sparing L
Gleason 8
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Test Performance
100
90
True positive rate (%)
80
High specificity reading
70
60
Sensitivity 60-70%
Specificity 80%
50
40
30
20
10
0
0
10
20
30
40
50
60
70
80
90 100
False positive rate (%)
Engelbrecht et al Eur Radiol 2002
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Interpretation
Spec
Sens
Acc
95
38
70
88
50
71
90
15
73
Bulge
79
46
72
Overall impression
72
68
71
Neurovascular
Bundle Asymmetry
Obliteration rectoprostatic angle
Extracapsular tumor
Yu KK et al. Detection of extracapsular extension of
prostate carcinoma with endorectal and phased-array coil
MR imaging: multivariate feature analysis Radiology 1997
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Staging
Incremental Diagnostic Value - MRI
Base Model
•  PSA & clinical stage
•  Gleason
•  max % & sum of core
•  PNI
n=344
216/344 spectroscopy
MRI + base model
better than
clinical + biopsy p<0.02
Wang et al Radiology 2004
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Staging
n
MRI
Partin
Partin+MRI
T1/2 <=G6 PSA<10
T1/2 G7|PSA 10-20
T3/4 >G7|PSA>20
Wang et al Radiology 2006
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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3T with Endorectal Coil
accuracy 83%, sensitivity 64%, specificity 98%
Futterer JJ et al Eur Radiol. 2007 Apr;17(4):1055-65
Although high level evidence is lacking it
is generally felt that maximal local staging
accuracy can be best achieved by
performing imaging at 3T with an
endorectal receiver coil
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Staging
Nodal Disease
•  A very important issue but techniques are still
investigational and no technique beyond
morphology has as yet established itself for
application in widespread practice
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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MRI for Nerve Sparing Surgery
•  In high risk patients (<=25% of OCD) a
change of surgical plan was suggested in
78% (28/36) sites and was appropriate in
93% (26/28 )
•  93% of surgical plans correctly altered
–  10/12 conservative plans correctly suggested
–  16/16 aggressive
•  MRI helpful if more than 25% of cores
positive
Hricak Cancer 100:2655-2663
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Focal Therapy
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Tumor Volume - Multifocality
961 RP’S, 2393 foci (2.49/pt)
2.5
2.13
cm3
2
1.5
86% of ECE from largest tumor
1
0.39
0.5
0.17
0.09
0.04
4th
5th
mean volume
0
largest
2nd
3rd
P. Scardino, EAU 2006
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Extracapsular Extension
961 RP’S, 2393 foci
377 (16%) ECE, 86% from largest tumor
PSA
n
%
ECE
% from
largest
focus
% from
largest
and other
> 10
218
59
76
17
4 -10
470
30
92
5
<4
126
20
92
0
P. Scardino, 2006
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Sparse Tumors
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Histologic Patterns of Cancer with Normal ADC (Like PZ)
a
b
loose stroma and benign glands
loose stroma
Histologic Patterns of Cancer with Low ADC
c
d
malignant glands
e
fibrous/sclerotic region dense stroma
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Langer DL, van der Kwast, Haider et al Radiology 2008; 249:900-908.
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Dr.$John$Trachtenberg$
Visualase System
Treatment$temperature$map$
University#of#Toronto,#Toronto,#CA#
January#26,#2010#
#
Irreversible$damage$es9mate$
Treatment$Images$in$Axial$plane$
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
MR of Prostate and Prostate Cancer
apex
Tumor
Contour
base
Contours
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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In Bore MR Guided Focal Ablation
Real Time Planning
3D view, Sagittal.
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Real Time Needle Tracking
Template Registration
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Immediate Post Treatment MR
Apparent Complete Tumor Ablation
Damage (outer blue , 2.3 cc). Target (red, 0.47 cc)
98% Overlap
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Visualase Laser
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Hologic/Sentinelle Medical
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Transrectal
•  InSightec ExAbalte system
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Transurethral
Chopra R, Bronskill M et al
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Prototype$system$
MRIAcompaCble#system#developed#at#SHSC#for#delivery#of#MRIAguided#
transurethral#ultrasound#therapy#in#a#clinical#imager#(1.5/3T)#
a)
b)
c)
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Device$Inser9on$
1)
2)
3)
•  Manual#inserCon#outside#of#MRI#
•  InjecCon#of#gel#into#urethra#performed#to#ensure#good#acousCc#coupling#
•  Rigid#device#can#be#inserted#into#paCent#lying#supine#on#MR#table#
•  Final#posiCon#was#approximately#15A20°#elevated#from#horizontal#
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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Results$?$Histology$
•  ConCnuous#paWern#of#thermal#coagulaCon#observed#for#all#subjects#
•  Sharp#transiCon#between#100%#coagulaCon#and#normal#prostate#Cssue#
(<3#mm)#
Maximum$Temperature$
Contrast?enhanced$MRI$
H&E$stained$sec9on$
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
A
MR-Image-transverse-to-UA
PB
*
B
MR-Image-along-*
UA
PB
CV
TV
UA
E1
E2
E3
E4
E5
E7
E7
E8
CV
SM
RV
TV
5-mm
Figure 4: Example of the treatment planning strategy that will be adopted for the
proposed study. A) For each transverse slice that will be used to control heating, the
prostate boundary (PB), and cancer volume(s) (CV) will be traced in 3D using inDhouse
treatment planning software. A target boundary (TB) will be selected such that a
pattern of thermal coagulation will be generated within a target volume (TV) using
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
the transurethral ultrasound applicator (UA). The safety margin (SM) away from the
cancer volume, and close to critical structures such as the rectal wall will be 4 mm to
avoid damage. In the vicinity of the CV, the target volume will extend to the prostate
boundary. B) The extent of the TV along the device is determined by the number of
activated elements (E1..N) along the UA required to cover the entire CV with a 4 mm
treatment margin on either side, as shown in the figure.
40
Post-MRI Status
•  We are overflowing with referrals
•  Need for appropriateness criteria
•  We are solving the sampling problem
–  Patients with prior negative biopsy
•  Better prognostication
–  Better selection for active surveillance
•  Image guidance for therapy
–  Focal therapies
–  Dose escalation
–  Salvage
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
Medical Imaging – Princess Margaret Hospital – University Health Network – Mount Sinai Hospital – University of Toronto
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