Grand rounds radiology

Prostate Cancer: Role of Radiology
pollev.com/nelly
Nelly Tan

Objectives
● Quiz
● Background
● Prostate MR Basics
● PIRADS
● Index tumors
● Imaging guidance: biopsy & treatment
● Surgical Planning
● UCLA Rad-Path
● Research
●

Disclosure
• Center Translational Sciences Institute
K30 Clinical Research Program
• UCLA SPORE
• Department of Radiology Rad-Path

Quiz
What is the
location?
A. Peripheral zone
B. Transitional zone
Quiz Intro Basics PIRADS Index Biopsy Tx Sx RadPath Project

Quiz
Quiz Intro Basics PIRADS Biopsy Tx Sx RadPath Project

Quiz

Quiz
For peripheral
zone cancers,
which is the first
sequence to
evaluate per
PIRADSv2?
A. T2
B. DWI
C. DCE

Quiz
For transitional
zone cancers,
which is the first
sequence to
evaluate
(PIRADSv2)?
A. T2
B. DWI
C. DCE

Quiz
Select the TRUE statement:
A) MRI identifies 70-80% of all size lesions
B) MR has higher detection in the prostatic
apex compared to mid / base lesions.
C) Predictive probability of MR for index
lesion is high
Nelly Tan : ntan@mednet.ucla.edu

Quiz

Quiz
Options for this man
with GS6 includes:
A. Active Surveillance
B. Focal Therapy
C. Radiation
D. Radical
Prostatectomy

Quiz
All of the following are local treatment
options EXCEPT:
A. Laser
B. Cryoablation
C. HIFU
D. RFA

Introduction
• Prostate cancer is the second leading
cause of cancer deaths
• Risk stratification is the most important
predictors for survival
– Gleason score, PSA, DRE
• Gleason score: most important
• US guided systematic biopsy standard
– 15% PPV for prostate cancer

Introduction
• Current models underestimates Gleason
in 30%
• Treatment related complications (erectile
dysfunction, incontinence) in up to 50%
• Poor prognosis when advanced, but most
indolent
• MR may improve risk stratification
– Identify more appropriate pts who need tx

Introduction
• Role of radiology?
– Diagnosis
– Image guided Biopsy
– MR guided focal therapy
– Surgical planning

Prostate anatomy

Market
• Study volume of Prostate MRI at UCLA as been on a
steady incline.
• Study volume of Abdominal MRI over the same
interval demonstrates a plateau.

• Conventional MRI (T1, T2)
• Dynamic-contrast enhancement (DCE)
• Diffusion-weighted imaging (DWI)
• Each component adds incremental value
Multi-Parametric MRI

Conventional MRI
• 3 Tesla magnet
• Endorectal coil for surgical planning
• On T2-weighted
– Depicts zonal anatomy
– Prostate cancer: low signal
– Limitations: hemorrhage, BPH

Normal
T2WI Examples
GS4+3

Diffusion-Weighted Imaging
(DWI)
• Evaluates water molecule motion
• Densely packed tissues have less motion
• Quantitative measure:
– apparent diffusion coefficient (ADC)
• Prostate cancer: Restricts; ADC correlates
with Gleason score
• Limitations: BPH, blood, distortions

DWI/ADC Examples
GS 4+3
GS 4+3
GS 5+4
Normal

Dynamic Contrast Enhanced MRI
(DCE)
• Assesses vascular perfusion
• Images acquired before and after contrast
• Malignant tissue:
– chaotic structure, high permeability
• Qualitative & quantitative measures (Kep,
Ktrans, AUC)
• Prostate cancer: high in all parameters
• Limitations: prostatitis, GS3+3, small
tumors

DCE Example
GS4+5GS3+3
Normal GS4+3
GS3+3
GS5+3
normal

Companion case
GS 4+3
Multi-Parametric MRI
T2WI DCE
DWI

ACR Appropriateness Criteria
Clinical Scenario Rating
Multiple negative prostate biopsies, but there is concern for prostate cancer
based upon rising or persistently elevated serum markers suggestive of cancer.
7
Prostate cancer diagnosed on biopsy, patient at high risk for locally advanced
disease and metastases (AJCC Groups III and IV).
Example: PSA ≥20 or Gleason 8-10 or clinical stage T2c or higher.
8
Prostate cancer diagnosed on biopsy, patient at intermediate risk
for locally advanced disease and metastases (AJCC Groups IIA or IIB).
Example: PSA 10-20 or Gleason 7 or clinical stage T2b.
7
Prostate cancer diagnosed on biopsy, patient at low risk for locally advanced
disease and metastases (AJCC Group I)
5
ACR Appropriateness Criteria 2012 https://acsearch.acr.org/docs/69371/Narrative/

http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/PIRADS/PIRADS%20V2
What is the performance?

PI-RADS Category
• 1 – Very low (clinically significant cancer is
highly unlikely to bepresent)
• 2 – Low (clinically significant cancer is unlikely to
bepresent)
• 3 – Intermediate (the presence of clinically
significant cancer is equivocal)
• 4 – High (clinically significant cancer is likely to
be present)
• 5 – Very high (clinically significant is highly likely
to be present)

PIRADS 2
DW
Peripheral Zone
31-2 4-5
DCE
+-
3 4

Quiz
For peripheral
zone cancers,
which is the first
sequence to
evaluate?
A. T2
B. DWI
C. DCE

PIRADS 2
T2
31-2 4-5
DW
5≤4
3 4
Transitional Zone

Quiz
For transitional
zone cancers,
which is the first
sequence to
evaluate?
A. T2
B. DWI
C. DCE

0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1, n=0 2, n=28 3, n=116 4, n=91 5, n=53
MR Overall Score
GS 8-10 GS 4+3 GS 3+4 GS 3+3
ACR PI-RADS
http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/PIRADS/PIRADS%20V2

Features Impacting Detection
Tan, N. Margolis DM, Reiter RE, Raman SS. AJR Am J Roentgenol. July 2015
Le, J , Tan, N. Margolis DM, Raman SS, Marks L, Reiter e. Euro Urology.

Features Impacting Detection

Discussion
• PCa lesions missed by mpMRI were
– smaller in size
– higher proportion with low grade PCa
– more often satellite lesions
– more commonly located at the prostatic apex.

67 yo M, PSA 4.6  6
Index GS 3+4 focus detected
Apical GS 3+3(5mm) missed
GS 3+3 missed

Strength or Limitation
• Majority of the satellite tumors were missed by MRI.
• Does that matter?
• Noguchi et al.17 evaluated the impact of satellite
tumors on PSA recurrence after prostatectomy.
• Secondary cancers in multifocal prostate tumors did
not adversely influence the results of biochemical
failure.
• Gleason pattern 4/5 in the biopsies and
prostatectomy specimen most powerful predictors of
biochemical failure after prostatectomy.
Noguchi M, Stamey TA, McNeal JE, Nolley R. Prognostic factors for multifocal prostate cancer in radical
prostatectomy specimens: lack of significance of secondary cancers. J Urol. 2003;170(2 Pt 1):459-463.

Strength or Limitation
• Findings suggest identification of the
solitary or the index lesion may be the
most important predictor of PSA
recurrence.

Strength: Index Lesion
• Metastatic cancers have monoclonal origins termed
index lesion.
• One of the most important purpose of mpMRI?
– Identify the index lesion
• At UCLA, detection rates:
– 70% of GS ≥7
– 80% of index lesions were detected (100% PPV)
• Others: 75.9% for index lesions in a multi-reader
setting.
• Can MR help localize tumor for targeted biopsy?
Liu W, et al. Nat Med. 2009;15(5):559-565.
Rosenkrantz AB, , et al.. AJR Am J Roentgenol. 2012;199(4):830-837.

Quiz
Select the TRUE statement:
A) MRI identifies 70-80% of all size lesions
B) MR has higher detection in the prostatic
apex compared to mid / base lesions.
C) Predictive probability of MR for index
lesion is high
Answer: C) Predictive probability of MR for
index lesion is high

Standard Systematic Prostate Bx
European Urology, 6 (31), February 2013, Pages 214-230
Uroinfo.ca

Targeted Biopsy
MRI guided US/MRI

UCLA’s experience: Targeted Bx
Tan N, Chen W, Asvadi N, Khooshnoodi P, Lu, DSK, Margolis DM, Raman SS. Radiology. Submitted
Sonn J, Margolis DM, Marks L. Euro Urology April 2014
Chang JJ1, Shinohara K, Bhargava V, Presti JC Jr. J Urol. 1998 Dec;160(6 Pt 1):2111-4. doi:10.1016/S0022-5347(01)62254-7
H. Singh, E.I. Canto, S.F. Shariat, et al. J Urol, 171 (2004), pp. 1089–1092
In-Bore MRI
(n=106)
US/MRI
(n=105)
TRUS only
Overall
Detection
59 % 34 % 10-17%
Gleason score
≥7
65 .0 % 44 % ~30%
Peripheral Zone
Transition Zone
41%
59%
66%
44%
77%
23%
# Cores 6 >12 >12

Case: Prostate MR
T2
ADC= 800b1400
DCE

MRI
• 2.6 cm left anterior central mass with
restricted diffusion and increased
perfusion.
• Overall suspicion: 5/5

US/MR fusion bx
• Pathology: BPH
• Referred for MR guided prostate bx

MR guided prostate bx

MR prostate bx pathology
• GS 3+4=7 involving multiple core
fragments
• Patient under radiation

Treatment Planning: RALP
• Preop eMRI
• Neurovascular bundle
– sparing vs. non-nerve sparing
• Recovery of urinary continence, EBL
Tan, N. Margolis DM, Reiter R, Huang J, Raman SS. Abdom Imaging 2011, Oct
Quiz Intro Basics PIRADS Index Biopsy Sx Tx RadPath Project

UCLA’s experience: RALP
• Influence of pre-op eMRI to spare NVB
• Of 104 pts, 29 (27.8%) had change
– 17 (59%) changed to nerve sparing
– 12 (41%) changed to resection of NVB
• Positive surgical margins rates:
– 6.7% (7/104).
• 6(87%) pts had no change in the operative plan
– All had NVB resected due to T3 on MRI
• 1 pt: MR changed plan to resect NVB
McClure T, Margolis D, Reiter R, Raman S. et al. Radiology 2011

MRI in assessing pT2 v. pT3
Stage, Imaging Versus Surgery
Pathologic
Imaging T2 T3
T2 91 4
T3 5 4
Sensitivity/Specificity 0.50 0.95
Positive/Negative
Predictive Value
0.44 0.96
Accuracy 0.91
McClure T, Margolis D, Reiter R, Raman S. et al. Radiology 2011 (in press)

59 yo GS3+3 PCa 2005 on Active Surveillance
(x 4 negative subsequent TRUS bx)
• MRI: 2.6 cm Lt mid
peripheral gland
(suspicion 5/5)
• US/MR fusion bx:
Gleason 3+3
• Tx?
ADCT2
DWI, b=1400

• No complications
• PSA 1.4 0.7
• Reported
improved LUTS
Post-Laser Contrast-T1 Axial
Post-Laser Contrast-T1 Sag Post-Laser Contrast-T1
Pre-procedure DCE

Quiz Question
Options for this man
with GS6 includes:
A. Active Surveillance
B. Focal Therapy
C. Radiation
D. Radical
Prostatectomy
Answer: depends

MR guided Focal Laser Ablation
• Focal Laser Ablation was successfully
performed in all 8 subjects.
• Ablation volume of 3 cc or 7.7% of
prostate volume.
• PSA declined in 7 men (p<0.01).
• At follow-up MR-US bx, PC was not
detected in the ablation zone in 5 men, but
was present outside the treatment margin
in 6 men.
Natarajan S1, Raman S2, Priester AM3, Garritano J3, Margolis DJ2, Lieu P4, Macairan ML4, Huang J5, Grundfest W3, Marks LS6 J Urol. 2015 Dec 31.
pii: S0022-5347(15)05540-8. doi: 10.1016/j.juro.2015.12.083. [Epub ahead of print]

High Intensity Focus Ultrasound
US guided: Ablatherm , Sonable MRI guided: InSightec (hemi)

US guided HIFU
•Sebastien Crouzeta, b, , et al Whole-gland Ablation of Localized Prostate Cancer with High-intensity Focused
Ultrasound: Oncologic Outcomes and Morbidity in 1002 Patients doi:10.1016/j.eururo.2013.04.039

MR-guided Cryoablation
Afshin Gagni et al European Radiology August 2012, Volume 22, Issue 8, pp 1829-1835

Cryoablation
• MR guided cryoablation feasible in 10/11
patients.
• Mean ice-ball volume was 53.3 ml.
• Mean PSA nadir was 0.33 ng/ml
• Mean hospitalization was 5 days
• Complications included a urethro-rectal
fistula, urinary infection, transient dysuria
and scrotal pain.

Treatment Options

Rad-Path Database

Rad-Path Database
• How do we do it?
– Multi-disciplinary Team: Radiology, Pathology,
Urology, Computer Vision and Imaging Biomarker
Center (CVIB), Medical Imaging Informaticist
– Goal: to translate data into information
– Obtain Clinical, Biopsy, Imaging, Pathology using PI-
RADS structured reporting
– GU Radiologist and Pathologist Match
– Medical informaticist links the data to EHR
– Web interface provides dynamic statistics of
performance, online interface to query and extract
data
– Near future: incorporate genome data

Multi-disciplinary effort
Radiology
Radiologists (and residents)
MII
CVIB
MR Physicists
Office of Research
Pathology
Urology

Decision Support
Accuracy 0.71 (comparable to radiologists)
N Tan, A Moshkar, N. Asvadi, F. S. Raman Scalzo. Accepted for ISMRM 2016

Acknowledgments
• Steven Raman, MD
• David SK Lu, MD
• Daniel Margolis, MD
• Robert Reiter, MD
• Jiaoti Huang, MD
• Dieter Enzmann, MD
• David Y. Lu, MD
• Polly Kay, RN
• Afsoon Moazzez, MBA
• Sandra J Smith MBA
• Brenda Brown, MA
• David Y. Lu, MD
• Kevin King, MD
• Htwe Khin, JD
• Heidi Coy, BA
• Pooria Khoshnoodi, MD
• Martin Lin, MD
• Holden Wu, PhD
• Kyung Sung, Phd
• Weixia Yu, PhD
• Will Hsu, PhD
• Wenchao Tao, MD
• Mahesh Nagarajan, PhD
• Preeti Ahuja, PhD
• Nazanin Asavdi, MD
• Amin Moashkar, MD
• Hector Alcala, PhD
• Luyao Shen, MD
• Porphan Wibulpolprasert, MD
• Fabien Scalzo, PhD
Departments
• Dept of Radiology
• Dept of Urology & Pathology
• Computer Vision Imaging Biomarker
• Medical Imaging Informatics
• Dept of Computer Science
• Office of Research

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