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

2. PSA Screening
Charles Chabert

3. European randomised Screening for Prostate Cancer
Charles Chabert

4. 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

5. 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

6. 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

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

8. 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 was initially used
Initially sextant biopsies, in June 1996 these were lateralised
Italy transperineal biopsies
Charles Chabert

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

10. 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= %)
pT2 (57.6%)
pT3 (42.4%)
Charles Chabert

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

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

13. 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

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

15. 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 years
Enrolled at 10 centres
PSA> 4.0ng/ml indication for biopsy
Charles Chabert

16. Study Design 1:1 randomisation 76 793men Randomized
in Screening group
in control group
Charles Chabert

17. 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

18. PLCO
Charles Chabert

19. 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

20. 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

21. PLCO Results
Charles Chabert

22. Results
Charles Chabert

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

24. Results
Charles Chabert

25. 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
Both centers had pilot studies
Charles Chabert

26. 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

27. Lancet Oncology (online early publication)
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

28. CAP Mortality
Charles Chabert

29. 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

30. 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