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

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%)

Chabert pT2 (57.6%) pT3 (42.4%)

Charles Chabert

Prostate Cancer Mortality

31 Dec 2006 Median F/U 9.0 years

Charles Chabert

CAP Mortality

Screening 214 deaths

Control 326 deaths

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

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

Study Design

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

Charles Chabert

Screened Control

Prostate Cancer (7 years)

2820 2322

Prostate cancer(10 years)

F/U 67%

3452 2974

Gleason score 8-10 289 341

50% had Gleason 5 or 6

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 yearsCAP 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

“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.

Summary

Charles Chabert