1. PSA, PCA-3 and peace of mind in suspected prostate cancer
Kieran Jefferson
Consultant Urological Surgeon
Partner, Warwickshire Urology

2. Biography 2008 - 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

3. 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

4. NICE guidelines

5. Prostate cancer issues
Prevention
Screening/PSA/PCA-3
Management of localised CaP
Hormone ablation
Castration-resistant disease

6. 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

8. 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 cost-effective.

11. ERSPC trial 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

12. Why does screening
not save more lives?

14. 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

15. 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

16. 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

17. PCA-3 assay Bead capture of mRNA Amplification of captured gene
Hybridisation protection assay using labelled DNA probes

18. 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

20. 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

21. Management of localised CaP
Active surveillance
Radical prostatectomy
External beam radiotherapy
Brachytherapy
Not Cryotherapy/HIFU

25. 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

26. 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

27. Any questions? jefferson@warwickshireurology.com

28. Why does screening
not save more lives?

29. Why does screening
not save more lives?

30. Why does screening
not save more lives?