BMUS

Prostate Cancer Study day

MRI imaging and reporting

Oliver Byass

Objectives

• mMRI

• Pi-RADS

• PROMIS

• Cases

mMRI

Combination of standard MRI sequences

T2 (T1) and functional techniques

• Diffusion weighted imaging-DWI

• Dynamic contrast enhancement-DCE

PiRadsProstate Imaging and Data System

• Feb 2012 European Society of Urogenital

Radiology.

• Inspired by Bi-Rads scoring system for

breast cancer, Likert scoring system 1-5

for each mMRI modality and then

generates a final overall score 1-5 of the

radiologists impression.

T2 imaging

T2 was the basis of MRI

imaging of the Prostate.

Water is bright on T2.

Challenge lies with:

• post biopsy inflammation, bleeding

and scarring.

• Atrophic change, prostatitis,

Intraepithelial neoplasias (PIN)

• Post Traetment lesions

• Detecting small lesions

T2w-Peripheral Zone

I II

T2w-Peripheral Zone

IVIV

TRUSS 2013

PSA+DRE

TRUS BX

533

+Ve

324 60%

-VE

209 40%

mMRI MRI Fusion BX

Post biopsy artifact

T2w T1w

DCE

T2DCE

DCE

• PCa shows increased

neoangiogenesis

• Pca shows increased

capillary leakage

• Visually represented

with DCE

• Sensitive for

aggressive Pca in the

peripheral zone

DWI

T2DWI

DWI

DWI allows analysis of the

Brownian motion of water and

expresses it by a parameter

known as the apparent diffusion

coefficient.

• A high ADC value of >1 mm2/s

is likely to represent an

inflammatory.

• A significantly reduced ADC

value of <0.6 mm2/s is a

tumour.

Pirads-V1 Sum Score

T2w- Score 5 DWI-Score 5

Pirads ScoreDCE-Asymetric focal

location:2 points Type 3 curve : 3 points

Standardized MRI Reporting

Regio

nImag

e

Ax.T

2

Size

mm

T2-

PZ

T2-

TZ

DWI DCE Pi-

RAD

S

8p 14 17 5 5 5 15

Pi-RADS: “Clinically significant disease….”1- Sum score 3-4 :”Highly unlikely”2-Sum score 5-7 :”Unlikely”3-Sum score 8-9 :”Equivocal”4-Sum score 10-12 :”Likely”5-Sum score 13-15 :”Highly likely”

1

Pi-RADS score

Pi-RADS classification Definition Total score

T2,DWI,DCE

1 Most probably benign 3-4

2 Probably benign 5-6

3 Indeterminate 7-9

4 Probably malignant 10-12

5 Highly suspicious of

malignancy

13-15

Roethke M, Blondin D, Schlemmer HP, Franiel T (2013) PI-RADS classification: structured reporting for MRI of the prostate. Rofo 185:253–261

Accuracy of Pi-RADS v1

Overall Pi-

RADS

Sum-Score

T2w,DWI,DC

E

Number of

Patients (%)

Tumour

incidence

(%)

ESUR –

”clinically

significant

disease”

1 3,4 1(1%) - Highly unlikely

2 5,6,7 59(41%) 11% Unlikely

3 8,9 36(25%) 19% Equivocal

4 10,11,12 31(22%) 65% Likely

5 13,14,15 16(11%) 94% Highly likely

Evaluation of the PI-RADS Scoring System for Classifying mpMRI Findings in Men with Suspicion of Prostate CancerDaniel Junker, Georg Schäfer, Michael Edlinger, Christian Kremser, Jasmin Bektic, Wolfgang Horninger, Werner Jaschke, Friedrich AignerBiomed Res Int. 2013; 2013: 252939. Published online 2013 December 16.

• Overdiagnosis of unsignificant disease

• Missing important cancers

Methods

• Multicentre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-

biopsy against a reference test (template prostate mapping biopsy)

• Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy,

underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy.

• Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core

length 6 mm or longer.

Findings

• 576 of whom underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy.

• On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically

significant.

• MP-MRI was more sensitive (93%, 95% CI 88–96%) than TRUS-biopsy (48%, 42–55%;

p<0·0001)

• 44 (5·9%) of 740 patients reported serious adverse events, including 8 cases of sepsis.

Accuracy csPca TRUS-biopsy v TPM-Biopsy

TRUS-biopsy Sensitivity 48% (95% CI 42–55), positive predictive value 90%

(83–94), specificity 96% (94–98), negative predictive value 74% (69–78)

TRUS-Biopsy Sensitivity 47% in Hull 2013 csPca

Truss Biopsy

Sextant biopsy on radical prostatectomy

specimens

• 1st sextant biopsy 60% of cancer

• 1st + 2nd sextant biopsies 75% of cancer

• 1st 10 core specimen 78% of cancer

• 1st + 2nd 10 core specimens 90% of cancer

Fink, c et al Urology 2001;58,735-739

533 Trus Bx

Accuracy csPca mpMRI v TPM-Biopsy

Pie charts represent actual MP-MRI scores 1–5.

Sensitivity 93% (48%), positive predictive value 51% (90%), specificity

41% (96%), negative predictive value 89% (74%). (TRUSS)

Interpretation

• Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy safely and

diagnosis of 5% fewer clinically insignificant cancers.

• If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of

clinically significant cancer might be detected compared with the standard pathway of TRUS-

biopsy for all.

Diffusion weighted Imaging

• Free water molecules are in cells can be detected by T2 imaging. The Brownian movement of

protons within cells can be detected by DWI

• The motion of molecules within the cellular microenvironment is impeded by their interaction with

cellular compartments, including the cell wall and intracellular organelles.

• Restriction in the diffusion of protons is directly proportional to the degree of cellularity of the

tissue. (More sensitive than imaging free water (T2) in the detection of csPca)

Diffusion-weighted vs T2Movement of protons vs Quantity of water

Diffusion weighted Imaging–ADC Mapping

Graph illustrates the logarithm of relative signal intensity (SI) (y-axis) versus b

value (in this case, 0 and 500 sec/mm2) (x-axis) for tumour and normal tissue.

The slope of the “tumour line” is less than that of the line representing normal

tissue, which translates into lower signal on the ADC map.

DWI-V

ADC b1400

DWI

DWI T2

Number of biopsy-proven prostate carcinomas visible on only

diffusion-weighted images and ADC maps (blue); on only T2-

weighted images (yellow); and on diffusion-weighted images, ADC

maps, and T2-weighted images (green).

Figure from Woodfield C, et al DWI MRI of Peripheral Zone Prostate Cancer

AJR 2010

Pi-RADS v2 2015

• Standardize non invasive MRI

• Target clinically significant prostate cancer

• DWI is king in Peripheral zone

• T2 is king in Transitional zone

Pi-RADS v2 2015

Case 1

B0 DWI B700 DWI

ADC map

TR 4+3 60% R+L-ve

T2 Fusion biopsy

Case 2

B0 DWI B700 DWI

Case 2

ADC HR T2

Case 2

• 6mm focus

• 25% 1 core

• Gleason 4+3

• L5= 1% 3+3

• R3= 95%4+3

Clinical Details : Raised age specific PSA 3 sets of negative biopsies previous MRI left peripeheral

zone PiRADs 3/4 template prostate biopsy Benign. PSA now climbed 37.

B0 B700

Case 3

ADC HR T2

TL 4+4 35%, R-ve L 4+4 3%

MRI imaging and Reporting

• DWI is now king in the peripheral zone

• PiRADS v2

• DCE is no longer performed in Hull

• MRI and USS are complimentary

• Thank you

Early experience of Pathway A

• An extra 4 MRIs a week

• Manageable Prostate fusion list 2-3

patients per week

• 50% less biopsies?

11 a month instead of 20 a month1. PiRADS 1-3 PSA monitoring/no biopsy

2. Template biopsy- right test first time

3. Very few repeat biopsies

Pathway A

• PiRADS 5 – 2 cores if you can correlate (3

cores if you can’t)

• Drop DCE – Alters management in very

few patients (Peripheral zone DWI 3/5)

• Drop Template biopsies for Anterior

lesions.

Imaging of the Bone Matrix

• Healthy adult bone is in homeostasis between resorption of old bone by osteoclasts and synthesis

of new bone by osteoblasts.

• Generally, cancer cells activate osteoclasts and lead to destruction of bone.

• In prostate cancer metastases tumour progression is observed by osteoblastic pathways.

• Bone-seeking tracers will accumulate in the bone matrix but not in cancer cells. Thus, radiotracer

uptake might be seen in cases of tumour regression with ongoing bone formation, “treatment

response” phenomenon. Degenerative bone disease, such as osteoarthritis, can also be avid for

these tracers and mimic metastatic disease.

• Bone scan uses 99mTc-labeled diphosphonates, including methylene diphosphonate (99mTc-MDP)

and hydroxymethylene diphosphonate (99mTc-HMDP).

• Sodium fluoride (NaF) is an inorganic chemical compound that dissolves to give separated

Na+ and F− ions. Its radiolabeled form, 18F-NaF rapidly exchanges for the hydroxyapatite’s

OH− ion, forming 18F-fluorapatite

• 18F-NaF PET is more accurate than a conventional bone scan or SPECT in the diagnosis and

characterization of metastases to bone prostate cancer

Wondergem M, van der Zant FM, van der Ploeg T, Knol RJ. A literature review of 18F-fluoride PET/CT and 18F-choline or 11C-choline

PET/CT for detection of bone metastases in patients with prostate cancer. Nucl Med Commun 2013; 34(10):935–945

There was no statistically significant discordance of these methods compared with

each other or with the standard of reference (18F-NaF PET/CT vs DWI, p = 0.27; DWI

vs reference, p = 0.64; 18F-NaF PET/CT vs reference, p = 0.06).

Read More: https://www.ajronline.org/doi/full/10.2214/AJR.11.8351

AATs = amino acid transporters, AR = androgen receptor, BA = bombesin analog,

CT = choline transporter

18F-FACBC = anti-fluorine 18 (18F)-1-amino-3-fluorocyclobutane-1-carboxylic acid, 18F-FDG = 18F-fluorodeoxyglucose,

18F-FDHT = 18F-16β-fluoro-5α-dihydrotestosterone, 18F-FLT = 18F-fluorothymidine, 18F-FMAU = 18F-fluoro-methyl-

arabinofuranosyl-uracil, GLUT = glucose transporter, GRP-R = gastrin-releasing peptide receptor, hENT = human equilibrative

nucleoside transporter, MCT = monocarboxylate transporter, PSMA = prostate-specific membrane antigen, SMI = small

molecule inhibitor, TK = thymidine kinase, Y = antibody.

Choline

• Overexpression of choline kinase has been observed in cancer cell lines, as

well as in samples from human breast, lung, prostate, and colorectal

cancers.

• (PET) imaging of patients with prostate cancer, three radiolabeled forms of

choline are available: 11C-choline, 18F-choline, and 18F-fluoroethylcholine.

Half-life of 18F (ie, 120 minutes, compared with 20 minutes for 11C), which

obviates the need for proximity to a cyclotron.

• Tracer accumulation may also be observed in inflammatory processes,

benign prostate hyperplasia, benign tumours, and synchronous malignant

disease

• The strength of choline-based PET imaging appears to lie in the detection of

prostate cancer recurrence after radical prostatectomy or radiation therapy.

The results of a meta-analysis on this topic, investigators reported pooled

sensitivity and pooled specificity of 86% and 93%, respectively, for all sites

of disease.Evangelista L, Zattoni F, Guttilla A, et al. Choline PET or PET/CT and biochemical relapse of prostate cancer: a

systematic review and meta-analysis. Clin Nucl Med 2013; 38(5):305–314.

72-year-old man with newly diagnosed prostate cancer (Gleason score, 5 + 5 = 10). (a) 18F-choline

PET/CT shows focal tracer uptake in multiple bone lesions (arrows). (b) PET/CT image of the pelvis

depicts intense focal tracer uptake(c) Axial CT image shows minimal sclerotic changes in the left

acetabulum. (d) Corresponding axial T1-weighted MR image shows minimal hypointense changes in

the left acetabulum.

18F-Choline PET/CT of a 70-year-old man with recurrence of an increased PSA level (1.9 ng/mL) 6

months after radical prostatectomy. (a) Early coronal maximum intensity projection shows focal tracer

uptake in multiple lymph nodes (arrows). (b–d) Axial fused PET/CT images obtained at increasingly

higher levels in the pelvis show the absence of focal tracer uptake in the prostate bed in b but also show

intense focal activity in three pelvic lymph nodes (arrows in c, d).

Prostate-Specific Membrane Antigen

• PSMA is a transmembrane glycoprotein that is found on prostate epithelial cells, the small

intestine, renal tubular cells, celiac ganglia, and salivary glands. Its expression is 1000-fold higher

in prostate cancer than in other tissues, and the degree of PSMA expression is associated with

the time to progression and the probability of relapse.

• PSMA has been observed in a variety of solid nonprostate malignancies.

• Poorly differentiated prostate cancer with neuroendocrine differentiation may appear negative

at PSMA-directed imaging.

• Celiac ganglia can also express PSMA and were found to be positive at PSMA PET/CT in as

many as 89% of patients with prostate cancer. Because of their paraaortic localization just in front

of the crura of the diaphragm and their lymph node–like morphologic structure at CT, the celiac

ganglia can easily be misinterpreted as metastatic lymph nodes.

• 68Ga-labeled PSMA ligand is a promising agent that showed higher sensitivity and tumour-to-

background ratios than did choline PET/CT in patients with recurrent prostate cancer.

Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-

based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41(1):11–20.

Summary

• Local Diagnosis-mMRIde Rooij M, Hamoen EH, Fütterer JJ, Barentsz JO, Rovers MM. Accuracy of multiparametric MRI for prostate cancer detection: a meta-

analysis. AJR Am J Roentgenol 2014;202(2):343–351.

• Lymph node stageing

mMRI- Sensitivity 39% and Specificity 82%Hövels AM, Heesakkers RA, Adang EM, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with

prostate cancer: a meta-analysis. Clin Radiol 2008;63(4):387–395.

Choline PET- Sensitivity 73% and Specificity 79%Mohsen B, Giorgio T, Rasoul ZS, et al. Application of C-11-acetate positron-emission tomography (PET) imaging in prostate cancer: systematic

review and meta-analysis of the literature. BJU Int 2013;112(8):1062–1072

• Local Recurrance to Prostate Fossa

mMRI- Sensitivity 82% and Specificity 87% (post prostatecetomy)

Sensitivity 82% and Specificity 74% (post radiotherapy)

Wu LM, Xu JR, Gu HY, et al. Role of magnetic resonance imaging in the detection of local prostate cancer recurrence after external

beam radiotherapy and radical prostatectomy. Clin Oncol (R Coll Radiol) 2013;25(4):252–264

Choline PET- Sensitivity 75% and Specificity 82%Evangelista L, Zattoni F, Guttilla A, et al. Choline PET or PET/CT and biochemical relapse of prostate cancer: a systematic review and

meta-analysis. Clin Nucl Med 2013; 38(5):305–314