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Dr. Charles Chabert's study on PSA screening for prostate cancer, including methods, results, and conclusions. Explore the debate on efficacy and implications for early detection.
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PSA: Fact or FictionThe 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
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 Charles Chabert
Prostate Cancer Mortality • 31 Dec 2006 • Median F/U 9.0 years Charles Chabert
ERSPC 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 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 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