PSA: Fact or Fiction The debate as it stands Dr Charles Chabert

PSA Screening Charles Chabert

European randomised Screening for Prostate Cancer Charles Chabert

ERSPC Initiated in early 1990s Aim was to evaluate the effect of PSA screening on death rate from prostate cancer Specifically whether PSA screening could reduce the mortality of CAP by 25% Charles Chabert

Methods 182000 men Ages between 50-74 (core group 55-69yr) Seven European countries Randomly assigned into group offered PSA screening on average every 4 year Control group that received no screening Charles Chabert

Study Design Power of 86% to show a statistically significant difference of 25% or more in prostate cancer specific mortality with a p value of 0.05 Basis of F/U through to 2008 On basis of overall level of compliance of 82% & 20% contamination in the control group a 25% reduction in CAP mortality in screening arm equates to 14% reduction on intention to screen

Randomisation Charles Chabert 160 men died between identification and randomization Mean age at randomisation wa 60.8 years Little variation amongst countries Charles Chabert

Screening tests and indications for biopsy Most centres used PSA cut-off of >4.0ng/ml Some centres also used DRE and F/T ratios In Finland PSA cut-off of 10.0ng/ml between 1991-1994 was initially used Initially sextant biopsies, in June 1996 these were lateralised Italy transperineal biopsies Charles Chabert

Results 5990 CAPs detected in screening group and 4307 in control group Cumulative incidence of 8.2% and 4.8% respectively Incidence of bone scan positivity was 0.23 vs 0.39 per 1000 in SCR vs CON 41% reduction in Sc group (p<0.0001) Charles Chabert

Results TRUS Biopsy Gleason 6 Gleason >6 Screening Group 72.2% 27.8% Control group 54.8% 45.2% Chabert 13% 87% (GS=7 74% GS=8-10 13%) pT2 (57.6%) pT3 (42.4%) Charles Chabert

Prostate Cancer Mortality 31 Dec 2006 Median F/U 9.0 years CAP Mortality Screening 214 deaths Control 326 deaths Charles Chabert

ERSPC Divergence of curves at 7-8 years that continues Charles Chabert

Results: Intention to screen analysis PSA screening : significant 0.71 prostate- cancer deaths per 1000 after median F/U 9 years Relative reduction of 20% of CAP related death for men between ages of 55-69years 1410 need to be screened to prevent 1 death 48 men treated This can be reduced by not treating indolent cancers Charles Chabert

Prostate, Lung, Colorectal and Ovarian screening trial ( PLCO) Charles Chabert

Study Design Exclusion criteria: History of PLCO cancer, current cancer treatment and from 1995 having had >1 PSA test in preceding 3 years Between ages 55-74 years Enrolled at 10 centres PSA> 4.0ng/ml indication for biopsy Charles Chabert

Study Design 1:1 randomisation 76 793men Randomized 38 343 in Screening group 38 350 in control group Charles Chabert

Study Design 91% and 98% power to show a 25% and 30% reduction in CAP mortality Assumption of 100% compliance with the assignment of screening and control No reference made to the power of the study at time of this analysis Charles Chabert

PLCO Charles Chabert

PLCO Results Median F/U 11.5 years Compliance 85% PSA screening in control group 40% in first year Increased to 52% in 6th year Charles Chabert

Results Screened Control Prostate Cancer (7 years) 2820 2322 F/U 67% 3452 2974 Gleason score 8-10 289 341 50% had Gleason 5 or 6 Charles Chabert

PLCO Results Charles Chabert

Results Charles Chabert

Conclusion PSA screening associated with 22% increase in CAP diagnosis Compliance with screening 85%( expected 90%) No change on CAP mortality Charles Chabert

Results Charles Chabert

ERSPC & PLCO Similar goals for both studies Pilot studies in both Screening: execution of biopsies under study group not clinical judgement Treatment left to regional centres ERSPC 4 yearly PSA ( Sweden 2 yr) PLCO Pre-randomisation limited to 1 in prior 3 years Annual PSA & DRE then 2 yrs PSA Regional centres made call on TRUS Pilot studies to assess for logistics Contamination etc Conducted between 1991-1994 Both centers had pilot studies Charles Chabert

Take Home Points ERSPC shows effect of screening on CAP mortality at 9 years This amounts to 20% on intention to treat analysis and 31% for men who are screened ERSPC NNT=48 PLCO shows no difference Charles Chabert

Lancet Oncology (online early publication) 20 000 men Randomised (Swedish cohort from ERSPC) Median upper limit screening 69 (67-71) Primary end point prostate cancer specific mortality First planned report Median F/U 14 years CAP incidence 12.7% vs 8.2% RR in CAP death 44% 293 men need to be screened 12 diagnosed to prevent 1 CAP death Charles Chabert

CAP Mortality Charles Chabert

Summary “GPs should be offering a PSA test to 40 year old men in conjunction with a digital rectal examination (DRE) after discussing with them the subsequent potential issues.” “Those identified as being at higher risk should undergo regular tests; those at low risk should consider less frequent testing.” Charles Chabert

Summary “A PSA level higher than 0.6 in a 40 year old is considered higher risk, as is a level of higher than 0.7 in a 50 year old, and regular monitoring is recommended for these groups. “There is firm data that PSA testing reduces the risk of being diagnosed with advanced disease, and that treatment of prostate cancer at an early stage can lead to a reduced risk of death. Charles Chabert