mpMRI in Prostate cancerA Urologist’s Perspective

DiagnosisTreatment ChoiceSurgical Planning

Dr. Peter Heathcote, Adjunct Professor APCRC-Q QUT, Senior Urologist PAH and GPH

Age-adjusted death rate in US Men

LL Lung

Colon

Nerve-sparing radical prostatectomy

PSA Testing

Mortality results from the Göteborg randomised population-based prostate-cancer screening trialJonas Hugosson et al. Lancet Oncol 2010; 11: 725–32

20,000 patients randomisedMedian follow up 14yrsARR of death from CaP 0.9% -> 0.5%

“This study shows that prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes.”

What is the problem?

• Life time risk of being diagnosed with CaP is 17%

• 10000 men/yr diagnosed in Australia

• Life time risk of dying from prostate cancer is 3%

• 3000 men /yr die in Australia

SEER cancer statistics review 1975–2004. Bethesda, MD: National Cancer Institute,

2007 (http://seer.cancer.gov/csr/

1975_2004).

This is the problem!

The Goteberg study again*To prevent one prostate cancer death

293 men need to be screened12 men need to be diagnosed8 men need to be treated

Over-diagnosisOver –treatment

* Lancet Oncol 2010 11:725-32

What role mpMRI?

OVER-DIAGNOSIS?Reduce number of biopsies.

?Reduce number of insignificant cancers diagnosed.

BUTIs there a risk of missing significant cancers?

What role mpMRI?

• Over–treatment

Can MRI facilitate greater use of Active Surveillance?

Compare mpMRI to TRUS

**1003 patients 12 core TRUS v MRI/MRGB 2007-2014

MRI/MRIGB diagnosed 248(25%) high risk and 213(21%) low risk

TRUSGB diagnosed 211(21%) high risk and 258(26%) low risk

BUT not the same cancers in 30% cases

*223 patients 12 core TRUS v MRI/MRGB

MRI/MRGB diagnosed 93(41%) high risk and 6(3%) low risk

TRUSGB diagnosed 79(35%) high risk and 47(21%) low risk

BUT TRUSGB “missed” 29(13%) high risk cases diagnosed by MRIGB

TRUSGB “found” 5(2%) high risk cases missed by MRIGB

***150 patients compared 30 core TRUSGB to 1.5T & 3T TMRI (no MRGB)

PIRADS 1-2 NPV 100-94%

PIRADS 3-5 PPV 73-100%

“mpMRI/MRGB diagnoses more significant cancers compared to TRUS utilizing fewer biopsies and finding fewer insignificant cancers”

BUT BOTH modalities miss some significant cancers (5-13%)

**M. Minhaj Siddiqui et al JAMA. 2015;313(4):390-397. NCI

*Pokorny et al Euro Urol 6 6 (2 0 1 4 ) 2 2 – 2 9 Wesley, Brisbane

***Thomson et al J Urol Vol. 192, 67-74, July 2014 St Vincents Sydney

Compare MRI to standard mount Radical Prostatectomy (RRP)

Of those 50 34% had Gleason grade >= 7

i.e. 17 /157 (11%) have significant disease missed by mpMRI

H. Samaratunga et al 2015

Total reported

No. reported as

UNILATERAL on MRI

No. reported as UNILATERAL

on RRP

Number of tumours missed

by MRIPIRADS        

3 42 29 14 154 109 61 37 245 159 67 56 11

TOTALS 310 157 107 50Percentage   50.65% 68.00% 31.9%

Compare MRI to whole mount Radical Prostatectomy (RRP)(THE gold standard)

• 20 patients -> 80 tumours -> 47 high risk• MRI detected 36 of those 47 tumours (77%)• MRI detected ALL index tumours Rhee et al 2015, PAH/GPH

• 122 patients -> 283 tumours ->134 high risk• MRI detected 96 of those 134 tumours (72%)• MRI detected 80% of index tumours• MRI detected 72% of tumours > 1cm Le et al European Urology 67 (2015) 596-576. UCLA

TAKE HOME MESSAGE

• MRI finds more significant tumours than TRUS• MRI finds fewer insignificant tumours than TRUS

BUT• TRUS finds some tumours missed by MRI• MRI misses up to 28% of significant tumours in radical prostatectomy

specimens.

The solution to Overdiagnosis

Improved diagnostic accuracy requires a multimodal cooperative approach

between Urologists and radiologists

MRI/MRIGB/TRUSGBDRE, PSAv, PSAD.

What role mpMRI?

OVER-TREATMENTCan mpMRI facilitate selection of patients for Active Surveillance?

Active surveillance with selective delayed intervention is the way to manage ‘good-risk’* prostate cancerLaurence Klotz University of Toronto**

*Gleason score 6 or less PSA less than 10ug/L Non palpable disease or small nodule Less than 1/3 cores positive Less than 50% involvement of any core

**Nature Clinical Practice Urology March 2005 Vol 2 No 3

Active SurveillanceKlotz et al 2010 J Clin Onc 28: 126-131

N = 452

Median follow up 7yrs

Cancer specific survival 97%

Bul M, Zhu X, Valdagni R, Pickles T, Kakehi Y, Rannikko A, et al. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol. 2013;63:597–603.

BUT!!

Only 1 in 3 choose AS over active treatment**

Only 2 in 3 stay on surveillance (Klotz et al)

**Daubenmier et al 2006 J Urol 67:125-130

Active Surveillance

• Why has take up of AS has been incomplete?• Only 1 in 3 opt for AS• Only 2 in 3 stay on AS

• Literature not yet mature, short follow up• Risk of undergrading

• Up to 33% of AS cases have higher Gleason Grade on repeat biopsy or subsequent radical prostatectomy. (Porten et al J Clin Oncol 2011;29:2795-800)

Active SurveillanceImproved diagnostic accuracy requires a multimodal

cooperative approachbetween Urologists and radiologists

MRI/MRIGB/TRUSGBDRE, PSAv, PSAD.

• Guidelines starting to include MRI in AS protocols• TRUS biopsy numbers have fallen by 17% in the last

4yrs*

*MBS

MRI planning in Robotic Prostatectomy