Screening and Prostate Cancer Mortality. Gesellschaftliche und wissenschaftliche Aspekte des Screening beim Prostata-Krebs

Screening and Prostate Cancer Mortality Gesellschaftliche und wissenschaftliche Aspekte des Screening beim Prostata-Krebs Screening and Prostate Ca...
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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) ƒ ƒ ƒ

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)

ƒ

„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....“

ƒ

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 ƒ Swiss Health Survey, 2007 ƒ 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 ƒ Screening-test ƒ ƒ ƒ ƒ ƒ

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 ƒ Screening programme ƒ ƒ ƒ

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 ƒ False positive test results ƒ ƒ

Unnecessary anxiety Unnecessary diagnostic interventions

ƒ False negative test results ƒ

Necessary treatment may not be received

ƒ Prolongation of time with disease without prolonging life ƒ Overdiagnosis ƒ ƒ ƒ

Unnecessary anxiety / psychological burden Unnecessary diagnostic interventions Unnecessary treatment with potential harms

Screening and Prostate Cancer Mortality

Screening and incidence of PC

ƒ

L Essermann et al, JAMA 2009;302:1685-92

Screening and Prostate Cancer Mortality

Lifetime risk of PC ƒ PSA-testing has doubled the chance of a men being diagnosed with PC in his lifetime ƒ Lifetime risk in 1980:

1 in 11

ƒ 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 ƒ Mortality decreasing ƒ USA: ƒ

Intensive opportunistic screening

ƒ UK: ƒ

Screening not widely adopted

ƒ 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 ƒ „…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 ƒ „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 ƒ Risk of prostate cancer:

http://deb.uthscsa.edu/URORiskCalc/Pages/figure.js

Screening and Prostate Cancer Mortality

Estimation of individual risk: tools ƒ 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