Usefulness of screening I

Transcrição

Screening and Prostate Cancer Mortality
Gesellschaftliche und
wissenschaftliche Aspekte des
Screening beim Prostata-Krebs
NATIONAL PRIORITIES NKP 2005-2010
1. Tobacco Prevention
2. Early Detection: Breast, Cervix, Colon,
Prostate
3. Quality in Cancer Therapy and Care
4. National Cancer Registry
5. National Prevention Legislation
www.oncosuisse.ch
www.swisscancer.ch
T
Cancer death in men US
Jemal A, Cancer Statistics 2009
T
5
Weiland; Deutsches Ärzteblatt 2006
Cancer: Global Challenge
Inzidenzraten steigen weltweit kontinuierlich an vgl 2000 v 2020
Weltweit neue Krebsfälle
2002
2010
2020
2030
20.3
Mio
16.5
Mio
10.9
Mio
13.0
Mio
Gehirn
Mult. Myelom
Ovar
Leber
Inzidenz 2020
Leukämie
Gastroint.
RCC
NHL
Lunge
Blase
Prostata
Colo-Rectal10.1 million
Brust
0 50 100 150 200 250 300
Jährliche Rate
The Cancer Atlas 2006
Incidence chart for 5 major EU countries
Globocan 2002 & internal figures
400
`000
Screening background
• Screening:
–
–
–
testing of potentially healthy populations
Identification of people who may have the disease
Not diagnostic
• Aim of screening:
–
–
Detection of disease before the onset of symptoms
Improvement of outcome due to better prognosis of
early stage disease
Optimal screening test
Essermann JAMA 2009;302:1685-92
Hintergrund
1.
Kanadische Screening Studie (Labrie 1999 Prostate),
randomisiert, 46‘000 Männer
Conclusion: a 3.25 odds ratio in favor of screening and
early treatment (P < 0.01)
2.
Schwedische Studie (Sandblom 2004 Eur Urol),
randomisiert, 9’000 Männer
Conclusion: no significant difference in total or prostate
cancer-specific survival between the groups
A.Omlin & Ch. Rothermundt
• 73‘000 Männer
• 55-74 Jahre
• Randomisiert: jährliches Screening
oder follow-up
• 10 US Zentren
• Median follow-up: 10 Jahre
BEMERKUNGEN
Kontaminationsrate (PSA Testung) in Kontrollgruppe:
40% im 1. Jahr, 52% bis im 6. Jahr
34% aller Patienten hatten eine PSA Bestimmung vor
Eintritt in die Studie
Patienten mit Neudiagnose Prostata-Karzinom bis zum 10.
Jahr verstorben:
312 in der Screening Gruppe und
225 in der Kontrollgruppe:
dh. excess mortality 87
5990 prostate cancers
in the screening group
and 4307 in the control
group
Gleason score of 7 or more
were 27.8% in the
screening group and 45.2%
in the control group
Beginn 1991
7 Länder
Median follow-up 9 Jahre
Kontrollgruppe: Behandlung
dezentral
Relative Reduktion der
PC-death probability: 20%
Um 1 Todesfall zu verhindern:
1410 Männer screenen
48Männer behandeln
1. Grösse der Studien
Power 90%, Signifikanz 5%
Ziel: 25% Reduktion in Prostata-Ca Mortalität
95% of male urologists and 78% of primary care physicians
who are 50 years of age or older report that they have had
a PSA test
Further analyses will be needed from these trials, as well as
from others — such as the PIVOT trial in the United States
and the PROTECT trial in the United Kingdom — if the PSA
controversy is finally to sleep the big sleep.
Ueberdiagnose Prostata-Ca seit PSA-Screening 1986
(Welch JNCI 2009)

1 Mio mehr Männer mit Prostata-Ca behandelt /23J
< 50Lj
7x häufiger (1.3 zu 9.4 per 100 000)
50-59Lj:
3-4x häufiger (58.4 zu 212.7 per 100 000)

„Most of this exzess incidence must represent overdiagnosis
..patients are needlessly exposed to hassle factos of treatment,
financial implications and anxiety with becoming a cancer patient....“

Editorial Otis Brawley: .......the highly pushed early detection message
has skewed public opinion and deligitmized the questions concerning
screening, causing many men to be overdiagnosed................ We
desperately need better tests ...to predict which patient has cancer
that is going to metastasize... and which cancer is destined to stay
local for the reminder of his life...
Statistical
modeling
serum signatures through discriminance analysis
Analysis of sera from BPH (n=15) and locPCa (n=16) patients reveal a 3-protein
signature that lead to an increased diagnostic accuracy when compared with PSA
Perfect discrimination
discriminance analysis
descriptive model
PSA
cross‐validation (predictive)
% accuracy
sensitivity
specificity
%
50.0
93.3
accuracy
71.0
p=0.0003
p=0.001
3-signature
p=0.021
p=0.008
p=0.028
p=0.079
sensitivity
specificity
%
81.3
80.0
accuracy
80.6
3-signature
plus PSA
Random discrimination
Quadratic discriminant analysis (accuracy)
n=31, Wilk´s lambda test (p values)
Jackknife leave one out cross‐validation
sensitivity
specificity
%
87.5
93.3
accuracy
90.3
Statistical
modeling
Analysis of sera from locPCa (n=16) and metPCa (n=21) patients reveal a 6-protein
signature that lead to an increased diagnostic accuracy when compared with PSA
discriminance analysis
Perfect discrimination
p=1*10E‐8
% accuracy
descriptive model
cross-validation (predictive)
p=0.02
p=0.173 p=0.007
p=1.4*10E‐7
p=0.05
PSA
sensitivity
specificity
%
66.7
93.8
accuracy
79.4
6-signature
sensitivity
specificity
%
100.0
100.0
accuracy
100.0
6-signature
plus PSA
p=0.922
Random discrimination
Quadratic discriminant analysis
n=37, Wilk´s lambda test
Jackknife leave one out cross‐validation
sensitivity
specificity
%
94.4
100.0
accuracy
97.1
Examination of the prostate in Switzerland
Swiss Health Survey, 2007
Examination of the prostate (any test, diagnostic or
screening, men 40 yrs +):
Age range
% ever had examination
Total
52.8
40 to 49 years
19.6
50 to 59 years
38.2
60 to 69 years
66.0
70 to 79 years
77.4
80 years +
83.2
BFS, Schweizerische Gesundheitsbefragung 2007
Usefulness of screening I
• Disease
–
–
–
–
Important health problem
Natural course of disease is understood
Identifiable pre-clinical phase
Effective treatment for early stage is available
Based on Wilson and Jungner, WHO 1968
Usefulness of screening II
Screening-test

Valid (sensitivity, specificity)
Safe
Easy to use
Acceptable costs
Test procedure is highly accepted
Usefulness of screening III
Screening programme

Ressources for follow-up diagnosis and treatment
are available
Adequate participation rate
Favorable relation of costs and benefits
Potential harms of screening
False positive test results

Unnecessary anxiety
Unnecessary diagnostic interventions
False negative test results

Necessary treatment may not be received
Prolongation of time with disease without
prolonging life
Overdiagnosis

Unnecessary anxiety / psychological burden
Unnecessary diagnostic interventions
Unnecessary treatment with potential harms
Screening and incidence of PC

L Essermann et al, JAMA 2009;302:1685-92
Lifetime risk of PC
PSA-testing has doubled the chance of a men
being diagnosed with PC in his lifetime
Lifetime risk in 1980:
1 in 11
Today:
1 in 6
OW Brawley et al., CA Cancer Journal Clinicians 2009;59: 264-73
Screening and PC mortality
Mortality decreasing
USA:

Intensive opportunistic screening
UK:

Screening not widely adopted
No significant differences in mortality between
the two countries
L Esserman et al., JAMA 2009;302: 1685-92
Risks and benefits of PC screening
„…an average man who gets screened is
48 times more likely to be harmed by screening
than he is to be saved by screening at 9 years
after diagnosis…“
P. Boyle, OW Brawley. CA Cancer J Clin 2009;59:220-4
Risks and benefits of PC screening
„The collective data clearly cannot justify mass
screening and indeed appear to justify support
for a recommendation against mass screening.“
P. Boyle, OW Brawley. CA Cancer J Clin 2009;59:220-4
What to do now?
At risk man
Is the man concerned about his prostate cancer
risk? If yes, got to next step
Assess risk factors for CaP, Life
expectancy, comorbidities
Some men may have such a low risk or such a shortened
life expectancy so as to benefit little from screening
If CaP is a potential concern, discuss risks and benefits
with the subject; determine his interest in screening
What to do now?
At risk man
Assess risk factors for CaP, Life
expectancy, comorbidities
Evaluate PSA and DRE
Prostate Biopsy
At present time, PSA and DRE are the best
initial screening tests.
Use a risk assessment tool to evaluate the
individual patient
Is risk sufficiently high for the subject,
perform prostate biopsy
Estimation of individual risk: tools
Risk of prostate cancer:
http://deb.uthscsa.edu/URORiskCalc/Pages/figure.js
Estimation of individual risk: tools
Risk of high-grade disease:
http://deb.uthscsa.edu/URORiskCalc/Pages/figure.jsp
Estimated and Actual Rates of Death from Breast Cancer among Women 30 to 79 Years of Age from
1975 to 2000 (Panel A) and under Hypothetical Assumptions about the Use of Screening
Mammography and Adjuvant Treatment (Panel B)
Berry, D. A. et al. N Engl J Med 2005;353:1784-1792