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

Biography 2008 - Partner, Warwickshire Urology 2006 - Consultant Urological Surgeon UHCW 2005-6 Post-CCT fellow in Uro-oncology 1998-05 SpR Urology, Southwestern Deanery 1994-8 Basic Surgical Training, Bristol 1990-3 Clinical Medicine, Oxford 1987-90 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 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 cost-effective.

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

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 Bead capture of mRNA Amplification of captured gene 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 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? jefferson@warwickshireurology.com kieran.jefferson@uhcw.nhs.uk

Why does screening not save more lives?

Why does screening not save more lives?

Why does screening not save more lives?