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Peter Albers, MD
Professor of Urology
Department of Urology
Düsseldorf University Hospital
Heinrich-Heine-University Düsseldorf, Germany
Why Prostate Cancer Screening ?
German and world-wide PCA Mortality ranks 2nd
RKI 2017 www.krebsdaten.de
Colorectal Cancer / Prostate Cancer
same mortality – no early detection program for prostate
mortality (2015):
13649 13900
Colorectal Cancer Prostate Cancer
(32900 men) (60700 men)
standardised
mortality (men)
2013: 21,6%
2018: 20.6%
(estimate)
= - 1%
standardised
mortality (men)
2013: 20.0%
2018: 19,4%
(estimate)
= - 0.6%
▵ ▵
RKI 2017 www.krebsdaten.de
mortality reduction method
PAP smear (cervical carcinoma) 64% coniotomy
colonoscopy (distal CRC) 50% endoscopy
PSA 27%* RP / RT / AS
stool test (CRC) 23% endoscopy
mammography (breast cancer) 20% (part.) mastect.
Comparison of Screening Programs
*Schröder F et al. ERSPC, Lancet Oncology 2014 after clearance for non-compliance
Comparison of Prostate Cancer Screening Trials
Martin RM et al. JAMA 2018, Schröder F et al. Lancet Oncology 2014, Andriole GL et al. JNCI 2012
PSA alone is not sufficient
Schröder F NEJM 2009
ERSPC
PSA > 3 ng/ml 25% PCA
15% significant
Aim of future PCA screening programs
reduction of overdiagnosis
Individualised PCA Screening
Potential Methods
• age-adapted risk groups
• hereditary risk
• mpMRT for „high risk“ patients
• kallikreins (4K)
• molecular markers (SNPs, MSI)
• combinations (risk calculators)
The „start early“ hypothesis
to reduce overdiagnosis
Vickers A et al. (MSKCC) BMJ 2013
„baseline“ PSA und prognosis
PSA at 45 yrs risk for metastasis
after 25 yrs
PSA < 1.1 ng/ml 1.38%
PSA > 1.6 ng/ml up to 9.82%
10x higher risk > 1.6 ng/ml
50% of men are „low risk“ and can be identified with
3 „life-time“ PSA values within 10 yrs below median
Lilja H et al, ASCO 2011
Hypothesis: 3 x PSA is enough !
The „start early“ data
Risk-adapted prostate cancer (PCa) early detection study based on a “baseline”
PSA value in young men – a prospective multicenter randomized trial (PROBASE)
Principle Investigators:
Peter Albers (Düsseldorf University)
Nikolaus Becker / Rudolf Kaas (DKFZ, German Cancer Research Center, Heidelberg)
90% 8% 2%
„baseline“ PSA
< 1.5 ng/ml
PSA test interval
5 yrs
1.5 -2.99 ng/ml > 3.0 ng/ml
PSA test interval
2 yrs
mpMRT and
biopsy
Accrual Feb 2014 – Sep 2018
10/2018: > 40.000 men, end of accrual: 12/2019
Carlsson S. et al Eur Urol 2017
NN to diagnose (after 17 yrs): 16
NN to diagnose (after 13 yrs): 32
(ERSPC: 27)
• early PCA screening reduces mortality
• is justified if active surveillance is performed in low risk cancers
Sweden: early screening (50-54 J) dramatically
reduces number needed to diagnose
Cost effectiveness of early screening (Markov model)
(PSA tests at age 55 – 57 – 59)
Heijnsdijk EAM et al Int J Cancer 2017
• organized PCA screening ist cost effective
Risk-adapted screening „take home“
• risk-adapted screening will prevent unnecessary
and „grey“ screening in 90% of men
• will identify 1-2% of men with early prostate
cancer
• can be terminated at age 60
• is cost-effective
• must not be followed by treatment in every case
(„active surveillance“ of low risk cancers)

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Peter Albers: Risk adapted screening

  • 1. Peter Albers, MD Professor of Urology Department of Urology Düsseldorf University Hospital Heinrich-Heine-University Düsseldorf, Germany Why Prostate Cancer Screening ?
  • 2. German and world-wide PCA Mortality ranks 2nd RKI 2017 www.krebsdaten.de
  • 3. Colorectal Cancer / Prostate Cancer same mortality – no early detection program for prostate mortality (2015): 13649 13900 Colorectal Cancer Prostate Cancer (32900 men) (60700 men) standardised mortality (men) 2013: 21,6% 2018: 20.6% (estimate) = - 1% standardised mortality (men) 2013: 20.0% 2018: 19,4% (estimate) = - 0.6% ▵ ▵ RKI 2017 www.krebsdaten.de
  • 4. mortality reduction method PAP smear (cervical carcinoma) 64% coniotomy colonoscopy (distal CRC) 50% endoscopy PSA 27%* RP / RT / AS stool test (CRC) 23% endoscopy mammography (breast cancer) 20% (part.) mastect. Comparison of Screening Programs *Schröder F et al. ERSPC, Lancet Oncology 2014 after clearance for non-compliance
  • 5. Comparison of Prostate Cancer Screening Trials Martin RM et al. JAMA 2018, Schröder F et al. Lancet Oncology 2014, Andriole GL et al. JNCI 2012
  • 6. PSA alone is not sufficient Schröder F NEJM 2009 ERSPC PSA > 3 ng/ml 25% PCA 15% significant
  • 7. Aim of future PCA screening programs reduction of overdiagnosis
  • 8. Individualised PCA Screening Potential Methods • age-adapted risk groups • hereditary risk • mpMRT for „high risk“ patients • kallikreins (4K) • molecular markers (SNPs, MSI) • combinations (risk calculators)
  • 9. The „start early“ hypothesis to reduce overdiagnosis
  • 10. Vickers A et al. (MSKCC) BMJ 2013 „baseline“ PSA und prognosis PSA at 45 yrs risk for metastasis after 25 yrs PSA < 1.1 ng/ml 1.38% PSA > 1.6 ng/ml up to 9.82% 10x higher risk > 1.6 ng/ml
  • 11. 50% of men are „low risk“ and can be identified with 3 „life-time“ PSA values within 10 yrs below median Lilja H et al, ASCO 2011 Hypothesis: 3 x PSA is enough !
  • 13. Risk-adapted prostate cancer (PCa) early detection study based on a “baseline” PSA value in young men – a prospective multicenter randomized trial (PROBASE) Principle Investigators: Peter Albers (Düsseldorf University) Nikolaus Becker / Rudolf Kaas (DKFZ, German Cancer Research Center, Heidelberg)
  • 14. 90% 8% 2% „baseline“ PSA < 1.5 ng/ml PSA test interval 5 yrs 1.5 -2.99 ng/ml > 3.0 ng/ml PSA test interval 2 yrs mpMRT and biopsy
  • 15. Accrual Feb 2014 – Sep 2018 10/2018: > 40.000 men, end of accrual: 12/2019
  • 16. Carlsson S. et al Eur Urol 2017 NN to diagnose (after 17 yrs): 16 NN to diagnose (after 13 yrs): 32 (ERSPC: 27) • early PCA screening reduces mortality • is justified if active surveillance is performed in low risk cancers Sweden: early screening (50-54 J) dramatically reduces number needed to diagnose
  • 17. Cost effectiveness of early screening (Markov model) (PSA tests at age 55 – 57 – 59) Heijnsdijk EAM et al Int J Cancer 2017 • organized PCA screening ist cost effective
  • 18. Risk-adapted screening „take home“ • risk-adapted screening will prevent unnecessary and „grey“ screening in 90% of men • will identify 1-2% of men with early prostate cancer • can be terminated at age 60 • is cost-effective • must not be followed by treatment in every case („active surveillance“ of low risk cancers)