Transcript PSA, PCA-3 and peace of mind in suspected prostate cancer

PSA, PCA-3 and peace of mind in
suspected prostate cancer
Kieran Jefferson
Consultant Urological Surgeon
Partner, Warwickshire Urology
Biography
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2008 2006 2005-6
1998-05
1994-8
1990-3
1987-90
Partner, Warwickshire Urology
Consultant Urological Surgeon UHCW
Post-CCT fellow in Uro-oncology
SpR Urology, Southwestern Deanery
Basic Surgical Training, Bristol
Clinical Medicine, Oxford
Medical Sciences, Cambridge
Potential conflict of interest
• Ipsen (Decapeptyl)
Paid consultant; principal trial investigator; book sponsorship; meeting sponsorship
• Wyeth/Takeda (Prostap)
Trial co-investigator; meeting sponsorship; paid lecturer; book sponsorship
• Glaxo (Dutasteride)
Trial co-investigator, meeting sponsorship, paid lecturer
• Astrazeneca (Zoladex)
Principal trial investigator; meeting sponsorhip; paid lecturer
• Novartis (Zoledronate)
Trial co-investigator; meeting sponsorship
• Sanofi Synthelabo (Docetaxel)
Meeting sponsorship; book sponsorship
NICE guidelines
Prostate cancer issues
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Prevention
Screening/PSA/PCA-3
Management of localised CaP
Hormone ablation
Castration-resistant disease
Prostate-specific antigen
• Seminal protein with probable role in
dissolving seminal clot
• Serum levels rise in prostate cancer, benign
prostatic enlargement, urinary tract
infection, acute urinary retention and after
urethral instrumentation or catheterisation
• Used since 1990s to detect prostate cancer
Who should have PSA testing?
• Pick winners (young/fit) - do a DRE!
• Men >40 with LUTS (beware UTI).
• Screening not currently recommended;
small survival advantage not deemed costeffective.
ERSPC trial
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182,160 men included (50-74 years)
Median follow-up 9 years
CaP in 8.2% screened; 4.8% non-screened
20% reduction in prostate cancer deaths
• Need to screen 1410 patients and treat 48 to
save one life after 9 years
Why does screening
not save more lives?
Who would I perform PSA test on?
• Any male with LUTS aged over 40 years
• Any healthy male over 50 years who requests
testing or has a family history
• ? Healthy males from age 50
• NOT asymptomatic males over 70
PCA-3
• Gene over-expressed in prostate
cancer (no protein product)
• DRE releases prostate cells into
urine
• Urine sample sent for central
analysis using RTqPCR
PCA-3
• Gene over-expressed in prostate cancer
(no protein product)
• DRE releases prostate cells into urine
• Urine sample sent for central analysis
using RTqPCR
PCA-3 assay
1. Bead capture of mRNA
2. Amplification of captured
gene
3. Hybridisation protection
assay using labelled DNA
probes
PCA-3 score
• PCA-3:PSA mRNA ratio in urine is ‘PCA-3 score’
• PCa-3 score offers specificity to complement
sensitive but non-specific serum PSA assay
• High score increases likelihood of +ve biopsy
Problems with PCA-3
• Most patients have a PCA-3 score giving a risk
of cancer between 25% & 50%
• It is labour-intensive/expensive and not
currently available for NHS patients
• No current role in prognostication
Management of localised CaP
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Active surveillance
Radical prostatectomy
External beam radiotherapy
Brachytherapy
• Not Cryotherapy/HIFU
Active surveillance
Aim
To individualise treatment
Patient
Fit for radical treatment
15-year life expectancy
Tumour characteristics
T1–T2 GS ≤7 Initial PSA <15
Monitoring
Frequent PSA testing
Repeat biopsies
Indications for treatment
Rapidly rising PSA
Symptomatic progression
Upgrading on biopsy
Parker Lancet Oncol 2004
Rationale for active surveillance
• Reduce overtreatment (probably > 50 patients
treated for each life saved)
• Frequent monitoring should enable detection
of higher risk patients (PSADT/PSA velocity)
• Regular re-biopsy minimises undergrading
Any questions?
[email protected]
[email protected]
Why does screening
not save more lives?
Why does screening
not save more lives?
Why does screening
not save more lives?