Prostate Cancer: Modernising The Diagnostic

PathwayMarc Laniado MD FEBU FRCS(Urol)

Consultant Urological Surgeon @marclaniado

www.windsorurology.co.ukmarclaniado@gmail.commarc.laniado@nhs.net

70% more prostate cancer cases by 2030

>75 y

65 to 74 y

50 to 64y

Age

stan

dard

ised

rate Cr

ude

rate

Ove

rall

num

bers

Source: Mistry 2011 BJC

We are here to arm ourselves against this threat

Without change, deaths from prostate cancer increase by 60% in 2030

Cancer Site 1990 Cancer Site 2010 Cancer Site 2030

Lung 39,176 Lung 34,859 Lung 44,986

Bowel* 19,365 Bowel* 16,013 Bowel* 19,032

Breast ** 15,141 Breast ** 11,556 Prostate 16,304

Stomach 9,795 Prostate 10,721 Pancreas 11,449

Prostate 8,926 Pancreas 7,901 Breast ** 11,133

Pancreas 6,935 Oesophagus 7,610 Oesophagus 10,087

Oesophagus 5,979 Stomach 4,960 Liver 7,918

Bladder 5,468 Bladder 4,907 Bladder 6,272

Ovary 4,528 Leukaemia 4,504 Leukaemia 5,500

Non-Hodgkin Lymphoma 3,998 Non-Hodgkin Lymphoma 4,452 Kidney 5,097

Source: Cancer Research UK 2013

Optimal outcome: reduce death rates!

1970 1980 1990 2000 2010 20200

20

40

60

80

100

120

Incidence and Mortality Rates per 100,000 by Year

incidence ratesmortality rates

Year

No

of m

en p

er 1

00,0

00 m

en

We want to see a decline in mortality

Risk prediction, mpMRI and targeted biopsies allow safer diagnosis in men with true risk

Use risk calculators to identify men at risk

3T multiparametric MRI can rule out people for further investigation

Targeted transperineal biopsies diagnoses accurately

Risk calculators beat human risk estimation consistently

Would you refer this man for investigation?

68 years old African American Man, Positive family of PcaNormal feeling small, prostatePSA 2.6no prior biopsy….

What about this man?

55 years oldwhite male, No family historyProstate feels abnormal and largePSA 0.3 no prior bx, recommendation? – Biopsy, right?

Search Google for SWOP Risk Calculator Start with SWOP “Risk calculator 3 + DRE”

Enter findings on rectal exam, DRE volume and PSA, click calculate

Results are given for risk of

any cancer and

advanced or high grade

cancer Refer if any risk > 20% or high grade risk > 4%

Large prostates -less likely to contain cancer compared to small prostates for the same PSA

Calculator is more accurate predictor

Any prostate cancer = 1% Advanced/high grade PCa=0.18%

Any prostate cancer = 22%Advanced/high grade Pca = 5%

Knowing your risk in relevant

Years after diagnosis

Dead from prostate cancer

Dead from other

causes

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

40% chance of dying at 10 years for high risk disease in PSA era in a 65 year old

Years after diagnosis

Dead from

prostate cancer

Dead from other

reasons

Gleason pattern 4 or 5

1 2 3 4 5

More testing in US associated with fewer deaths and faster fall than UK

4 fold faster fall and lower in US

Could low assessment rates for prostate cancer in UK be responsible?

Even simple PSA-based screening reduces prostate cancer deaths by 25%

Screening programmes only beneficial if little routine testing

20 – 30% reduction in death rates

No change in death rate

35 men needed to be diagnosed by screening to save 1 life at 12 years

PIVOT trial showed treatment benefits in high risk prostate cancer

Reluctance to test for prostate cancer has been overdone

Current Tissue Diagnosis Pathway is Unfit for Today

On standard unguided biopsies – even small lesions may seem to be important

Biopsy needles passing from rectum into prostate

Anterior

Posterior

Unguided or transrectal biopsies miss tumours esp. anterior cancers

Biopsy needles passing from rectum into prostate

Anterior

Posterior

Unguided biopsies may glance an important cancer, underrepresenting it

Biopsy needles passing from rectum into prostate

Anterior

Posterior

Multiparametric MRI localises prostate cancer and informs on the severity – Best Current Test

mpMRI (1) shows cancer as black areas

Histology shows cancer in red and MRI in black

mpMRI (2) Cancer is stiff and restricts diffusion of water molecules

Diffusion Weighted Imaging on ‘long B’ images shows cancer as white

Restricted diffusion by cancer is white

in this scan

mpMRI (3) early uptake of contrast indicates cancer

Rosenkrantz 2012

MRI “feels” areas you cannot touch with your finger: anterior tumours – often “no cancer” on TRUS biopsy

mpMRI report shows location and lesion scores

mpMRI lesion is scored from 1 to 5 indicating likelihood of significant cancer

Score Meaning

1 Not suspicious Highly unlikely to contain a clinically significant lesion

2 Not very suspicious Unlikely to contain a significant lesion

3 Ambiguous Ambiguous!

4 Suspicious Likely to contain a clinically significant lesion

5 Very suspicious Highly likely to contain a significant lesion

Significant lesion is more than 0.2cc or Gleason pattern 3+4 or higher

mpMRI score & report guides likely management

Score Meaning Management Plan

1 Not suspicious Observe

2 Not very suspicious Observe

3 Ambiguous Look at other risk factors to determine biopsy e.g.: PCA3 score >35, PSA density > 0.2 ng/ml/cm3 (PSA/prostate vol)

4 Suspicious Biopsy

5 Very suspicious Biopsy

Indications for mpMRI

• Anyone at risk of prostate cancer in whom diagnosis may be beneficial

• PSA > age threshold– 50-50y PSA > 3– 60-69y PSA > 4– 70y + PSA > 5

• BEFORE prostate biopsy• After negative biopsy without MRI• Active monitoring

After a Transrectal biopsy, 30 to 70% will have a positive biopsy, After a negative multiparametric

MRI only 3% have a positive biopsy

Many Advantages of MRI!!

Biopsies of mpMRI targets are more representative of the tumour severity

Fewer cores need to be taken and the highest grade and cancer length are found

Transperineal guided biopsies enable more reliable targeting and are safer

No life threatening sepsis or rectal bleeding

“Transfaecal” biopsies4% hospitalisation

A grid in front of the perineum positions the needle accurately

Using USS and MRI fusion, the needle is guided into exactly the correct place

Histology Report Guides Need for treatment

Prostate biopsy map

Optimal Prostate Cancer PathwayPSA

Risk any Ca >20%Risk high grade

PCa>4% or NICE PSA

Multiparametric MRI

Only 3% chance of prostate Ca - monitor outside hospital

Transperineal Targeted biopsies

Low risk localised

High risk localised

prostatectomyAS

Brachy

Focal Therapy

PSA>15 or mpMRI+

mpMRI-ve & PSA <15

Prolaris: new test on cell cycle proteins may improve prognosis over Gleason score

Prolaris added to existing risk scores enhances prognostication

O Gleason <7 O Gleason 7 O Gleason 8-10

15% of low risk (Gleason 6) have > 20% clinical risk

O Gleason <7 O Gleason 7 O Gleason 8-10

15% Gleason 6 > 20% risk

15% of high risk (Gleason 8) have < 20% clinical risk

O Gleason <7 O Gleason 7 O Gleason 8-10

15% Gleason 8+ <20% risk

When confident low risk cancer, focal ablation to target the lesion is an option

Optimal Prostate Cancer Pathway?PSA < 15

Risk any Ca >20%Risk

high grade PCa>4% or NICE PSA

Multiparametric MRI

Only 3% chance of prostate Ca - monitor outside hospital

Transperineal Targeted biopsies

Low risk localised

High risk localised

prostatectomyAS

mpMRI-ve & PSA <15

Brachy

Focal Therapy

PSA>15 or mpMRI+

Multiple guidelines advise on early detection

Advise men < 40 years: not to have PSA-based screening

• Prevalence– Caucasians 0.1%– African 2%

• Autopsy studies: low volume and low grade PC

Men aged 40 to 54 years screen if risk factors

• Family History– Prostate Cancer

• First degree 130% increase– Father 120% increase– Brother 200% increase

• Second degree 100%• More if age < 65 years and relative <

60 years

– Breast cancer• Mother 20% increase in risk (not

sister)

– BRCA2 gene 7 x increase in risk if age < 65 years

• Race– West Africa SMR 270– Caribbean SMR 200

Aged 55 to 69 : test after shared decision making based on values & preferences

• Check baseline mortality risk from other comorbid conditions

• Individual risk factors• How screening might

– influence overall life expectancy

– Morbidity from prostate cancer itself

– Morbidity from prostate cancer treatment

• Decision aids

Do not routinely screen > 70-74 years

• If screening, high grade disease is worth diagnosing– PSA > 10 ng/ml