Screening and Prostate Cancer Mortality
Gesellschaftliche und wissenschaftliche Aspekte des Screening beim Prostata-Krebs
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
T
Screening and Prostate Cancer Mortality
Cancer death in men US
Jemal A, Cancer Statistics 2009
T
Screening and Prostate Cancer Mortality
5
Weiland; Deutsches Ärzteblatt 2006
Screening and Prostate Cancer Mortality
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 and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
Optimal screening test
Essermann JAMA 2009;302:1685-92
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
• 73‘000 Männer • 55-74 Jahre • Randomisiert: jährliches Screening oder follow-up • 10 US Zentren • Median follow-up: 10 Jahre A.Omlin & Ch. Rothermundt
Screening and Prostate Cancer Mortality
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
A.Omlin & Ch. Rothermundt
Screening and Prostate Cancer Mortality
A.Omlin & Ch. Rothermundt
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
1. Grösse der Studien
Power 90%, Signifikanz 5% Ziel: 25% Reduktion in Prostata-Ca Mortalität
A.Omlin & Ch. Rothermundt
Screening and Prostate Cancer Mortality
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.
A.Omlin & Ch. Rothermundt
Screening and Prostate Cancer Mortality
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...
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
Usefulness of screening II Screening-test
Valid (sensitivity, specificity) Safe Easy to use Acceptable costs Test procedure is highly accepted
Based on Wilson and Jungner, WHO 1968
Screening and Prostate Cancer Mortality
Usefulness of screening III Screening programme
Ressources for follow-up diagnosis and treatment are available Adequate participation rate Favorable relation of costs and benefits
Based on Wilson and Jungner, WHO 1968
Screening and Prostate Cancer Mortality
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 Prostate Cancer Mortality
Screening and incidence of PC
L Essermann et al, JAMA 2009;302:1685-92
Screening and Prostate Cancer Mortality
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 Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
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
Screening and Prostate Cancer Mortality
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
A.Omlin & Ch. Rothermundt
Screening and Prostate Cancer Mortality
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
A.Omlin & Ch. Rothermundt
Screening and Prostate Cancer Mortality
Estimation of individual risk: tools Risk of prostate cancer:
http://deb.uthscsa.edu/URORiskCalc/Pages/figure.js
Screening and Prostate Cancer Mortality
Estimation of individual risk: tools Risk of high-grade disease:
http://deb.uthscsa.edu/URORiskCalc/Pages/figure.jsp
Screening and Prostate Cancer Mortality
Screening and Prostate Cancer Mortality
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