Mr Marc Laniado and Dr Tristan BarrettPut your heads together: MDT decision-making – pitfalls and patient outcomes

Bayer Radiology Academy Forum on Breast and Prostate MRI • 17 November 2017

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UKGDV04170006al Date of preparation November 2017

Dr Barrett: None to declare

Mr Laniado: Share ownership in Nuada Medical - a company that provides MRI-targeted transperinealprostate biopsies equipment

Disclosures

MDT Decision Making: Pitfalls & Patient Outcomes

Tristan BarrettMarc Laniado

UKGDV04170006al;November2017

MDT meetings contribution from medical specialists, nurses & allied specialties

Clinical Nurse Specialists

Multi-Disciplinary Meetings (MDM) aims: 1) More evidence-based practice

Multi-Disciplinary Meetings (MDM) aims: 2) Stop treatments outside accepted standards

MDMs evolve into treatment-decision making meeting (MDTM) at key points in patient journey

MDTM = forum for multi-disciplinary/professional advice & input on a patient’s management

Investigations Treatment

Follow up Ethical & social matters

Comorbidities

Practical problems

MDTM challenges

Too many patients Not enough time to discuss each patient

Missing information Too many meetings

MDTM transformation to be more effective

Public Health England guidance on PSA testing in asymptomatic men

Prostate Cancer Risk Management Programme, Public Health England 2016

Risk categorisation&

management options

Public Health England (& PCUK) advisedPSA threshold: 3 mcg/L, age 50 to 70

Threshold PSA: Over 50 years > 3 mcg/L45–50 > 2.5 mcg/L

Online calculator to predict chance of prostate cancer on systematic transrectal biopsy

http://www.prostatecancer-riskcalculator.com/seven-prostate-cancer-risk-calculators

mpMRI & mapping biopsies find more significant cancer compared to TRUS biopsy, so online

calculators underestimate risk

Reference standard

40% 37%

19% 0%

25%

50%

75%

100%

Transperineal mapping biopsy mpMRI +ve TRUS biopsy +ve

% o

f men

with

sig

nific

ant c

ance

r Significant

PSA>3or>2.5

(black/hardprostate/strongFH

Suspicionscore4,5

Suspicionscore1,2

Targeted±systematicprostate

biopsies

PSAmonitoring

PSAsurveillance/systematicbiopsies

No mpMRI

Suspicionscore3

50%

25%

25%

PSA density threshold = 0.15 ng/mL/cc

mpMRI

Based on PI-RADS score, go for biopsy

MRI-targeted biopsies very precise – hit the target accurately

1 Match axial T2/DCE MRI & USS

3 Biopsy on longitudinal2 Direct needle to correct location

4 Check on axial that in correct position

3 4 5

Pathologist examines slides & grades tumour severity by Gleason score

Gleason patterns

• Gleason score is sum of two Gleason patterns (a.k.a. grade)

• Two most common architectural patterns chosen

Targeted biopsies find greater amount & higher grade cancer compared with TRUS biopsies à more categorised as higher risk

4 MRI-targetedbiopsy cores

TRUS12 biopsy cores

Clinically significant (higher Gleason grade) 74% 24%

Proportion of +ve cores 44% 11%

Maximum cancer length on biopsy (MCL) 8 mm 4 mm

MRI-targeted biopsies lead to perceived prostate cancer risk inflation

Robertson 2014 Eur UrolMesko 2016 Am J Oncol

Risk classification after MRI-targeted & mapping transperineal prostate biopsies:

Gleason score & maximum cancer length

No treatment

Active surveillance

Treatment possibly

Treatment advisable

Treatment options are broad & unclear

?

Patient preferences can guide choices

Years after diagnosis

Dead from prostate cancer

Dead from other

causes

Active surveillance: 4% chance of dying after 10 y for low-risk disease in PSA era in 65 year old

Contains Gleason pattern 3 only

1 2 3 4 5

|Cuzick 2006 B J CancerAlbertsen 2007 J UrolLu-Yao 2009 JAMA

Prostatectomy more likely

Retention of urine

Urinary symptoms

Erectile dysfunctionInflammatory bowel diseaseYounger age

Radiotherapy more likely

ComorbidityScarred abdomen

Older man Short urethral length

Brachytherapy more likely

Low risk disease

Potent

Short urethral length

Focal therapy more likely

Base Mid Apex

Posterior tumours away from sphincter

Sphincter

Potent

Case 1

• 59 year old

• PSA 4.4 ng/ml• Gland volume = 30.5 ml• MRI: 10×5 mm high probability lesion at the right base PZ,

sector 2p• Pathology:

• Target cores: Right base 2/3 cores Gl 4 + 3 = 7. 50%, max core length 8 mm

• Systematic cores: Right apex 2/3 cores 3 + 3 = 6, 12%

• Systematic cores: Right base 3/3 cores 3 + 4 = 7, 25%

MRI-targeted biopsies: 4 + 3 = 7 (grade group 3)& systematic biopsies: 3 + 4 = 7 (grade group 2)

Base

What risk: low or high?

UCL definition: significant cancer

NCCN definition: unfavourable intermediate risk

SignificantTable shows NCCN risk groups for clinically localised

prostate cancer

CAPRA score: 7 (high risk)

Unfavourable intermediate risk disease requires treatment in most cases

AUA, ASTRO,

SUO 2017

guideline

Case 2

Patient on active surveillance

• Presented 2012

• Age 66 y, PSA 3.5 mcg/mL benign feeling prostate,

• Caucasian, ASA I, WHO PS 0, no FH of PCa

• Sexually active & minimal LUTS

• PMH

§ 2007 -ve transrectal prostate biopsies PSA 2.7, benign

§ 2005 low-risk, Non-Muscle Invasive Bladder Cancer (NMIBC)

§ 2007 BPH & GreenLight laser prostate ablation

mpMRI 2012 shows several lesions

• Index lesion: PI-RADS v2 score 4/5 left mid-gland anterior transition zone & AFMS

• Secondary area at left base intermediate

T2 DCE ADCImages from midgland

MRI-targeted transperineal biopsies showed Gleason Score 3 + 3 = 6, MCCL 14 mm

Gleason score 3 + 3 = 6, 14 mm, grade group 1

T2

DCE

ADC

What risk: low or high?

SignificantTable shows NCCN risk groups for clinically localisedprostate cancer

UCL definition: significant cancer

NCCN definition: low risk

CAPRA score: 2 (low risk)

Low risk disease: AS or whole gland radical treatment

AUA, ASTRO,

SUO 2017

guideline

Biomarkers add more information to pathology results

Cell cycle progression score: proportional to chance of dying

Dea

ths

from

pro

stat

e ca

ncer

Years from diagnosis

Low score

High score

10

30%

0

Prolaris: Cell Cycle Progression (CCP) Score

Low Prolaris

Bostrom 2015 Eur Urol

CCP score consistent with low-risk group - chose AS

Stone 2014 SUO, Cuzick 2015 AUA, Cuzick 2014 Recent Results

PSA values rising slowly over time

2017 (age 72): PSA 5.6, 10% free PSA, PSA density 0.13 ng/mL/cc

MRI shows enlarging anterior lesion

Role of MRI in active surveillance?

Retter 2017 EAU Annual Meeting #803

Case 3

• 79 year old

• Presenting PSA 10.98 ng/ml

• Gleason 4 + 3 left base PZ

• Underwent HIFU focal therapy 18 months ago

• Current PSA stable at 1.43 ng/ml

Gleason score 4 + 4 = 8 (grade group 4/5),maximum cancer core length 10 mm

Prebiopsy MRI Tumour map

What risk: low or high?

NCCN definition: high risk

SignificantTable shows NCCN risk groups for clinically localised

prostate cancer

CAPRA score: 6 (high risk) UCL definition: significant cancer

High risk disease requires treatment in most cases even in older men

AUA, ASTRO,

SUO 2017

guideline

Focal therapy chosen because this was his preference

Base Mid Apex

Posterior tumours away from sphincter

Sphincter

PSA stable over this time

0

2

4

6

8

10

12

PSA

1 week post focal HIFU MRI DCE shows the area treated

UnaffectedNeurovascular

bundle

Ablated cancer

Nerve bundle

Subtypes of FT: How focal?

• Hemi-ablation:treathalfthegland• Focal/zonal:treat≥2lesionsin1areaofthegland• Targeted/Indexlesion:treatthelargesttumour

• 1–2 weeks: ↑ in gland size • Reactive oedema and inflammation

• Amount depends on “focality” of treatment

• 3+ months: ↓ in gland size • Coagulative necrosis replaced with fibrosis

• Capsular retraction, scarring

Post treatment findings

Post treatment scarring/atrophyBaseline

4 months

Case 4

• 67 year old. PSA 9.6 ng/ml

• AP resection for ulcerative colitis 1981

• HoLEP in 2012 – benign histology

• Diagnostic problem – no rectal access

• Cannot perform DRE

• Cannot perform TRUS biopsy

• Cannot perform Transperineal US/MRI fused biopsy

Approaches adopted

• US-guided TP biopsyPCa in 7/7 with MRI Likert score 4–5 (1 case GS 6; 6 cases GS ≥7). 2 score 3 and 2 negative = no cancer

• MRI assisted CT-guided transgluteal2/2 case

• Other approachesUS: transperineal, transabdominal, or transurethralMRI: transgluteal