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Prostate Cancer: Modernising The Diagnostic
PathwayMarc Laniado MD FEBU FRCS(Urol)
Consultant Urological Surgeon @marclaniado
[email protected]@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