European Prostate Cancer Awareness Day 2019

1. PSA and risk stratification
How can we identify those men that can benefit
from early testing
A stepwise approach
M.J.Roobol

2. European Union and ERSPC mortality reduction
• 2015: 77,000 PC deaths
• ERSPC mortality reduction app. 30%
• 0.30 * 77,000 ≈ 23,000 less PC deaths
• European population: 515,052,778
• NNI to avoid one PC death: 22,727
NNI = Number Needed to Invite (several times) to avoid one PC death
NNI = 1/absolute risk reduction: (77,000/515M) – (54,000/515M) = 1/0.044*1000

3. Gender
• We will only consider men
• 0.49*515,052,778 = 252,375,861
• NNI to avoid one PC death: 10,965

4. Age
• Taking into account natural history
• Appropriate age range for screening 50/55-75 yr
• N= 55,287,068
• NNI to avoid one PC death: 2,400

5. PSA is a useful biomarker
Vickers et al. BMJ 2010;341:c4521 ERSPC Rotterdam, age 55-74 yr, initial screening, N=19,970
PSA % Cum %
< 1.0 35.7 35.7
1.0 - < 2.0 31.1 66.8
2.0 - < 3.0 12.6 79.4
3.0 - <4.0 7.1 86.5
4.0 - <10.0 11.2 97.7
>= 10.0 2.3 100.0
• Age 60: 25 yr follow-up: 0.2% risk of death from prostate cancer
with PSA < 1.0 ng/ml
• Men aged 55-75 ERSPC Rotterdam: 36% had PSA < 1.0 ng/ml
• PSA risk stratification: 0,64*55,287,068 = 35,383,723
• 10% less PC deaths avoided
• NNS to avoid one PC death: 1,707

6. Those special cases
• For Now:
BRCA1/2 or 1st/2nd relative with M+ PCa start
at age 40

7. Guidelines
PSA
(ng/ml)
Age 50-59 % of men Age 60-70 % of men
< 1.0 Postpone re-testing at
least 5 years
50% Stop further testing 30%
1.0-3.0 Test with 2 to 4 yr
interval
40% Test with 2 to 4 yr interval 45%
>= 3.0 Reflex testing 10% Reflex testing 25%
EAU: http://uroweb.org/guideline/prostate-cancer/?type=pocket-guidelines
https://www.mskcc.org/cancer-care/types/prostate/screening/screening-guidelines-prostate

8. PSA
• PSA is suitable as an initial risk stratification tool!
• Studies have shown that men (> = 60 yr) with PSA
levels < 1.0 ng/ml have very low chance of suffering or
dying from PCa (app 30-50% of men): STOP
• STOP testing men with limited life expectancy
• Men with intermediate PSA should be retested but
definitely not every 6 months/year
• PSA >= 3.0 ng/ml should NOT directly lead to biopsy (or
mpMRI)
• Reflex testing!

9. Effective possibilities
Diagnosis of
GS >= 7 PCa missed
Prostate biopsies
avoided
Costs per test
($)
PCA3 3-13% 46% 450
PHI 5% 36-41% 80
Free-PSA 23% 66% < 80
4K-panel 1.3-4.7% 30-58% 400-1000
STHLM-3 panel 1% 32% 285
Select-MDX 2% 42% 250-290
ERSPC Risk Calculator 12,5% cut-off 1% 33 % < 2
mpMRI targeted prostate biopsy 20% 27% 250-400

10. And now there is MRI and targeted biopsy
Risk stratification before MRI and biopsy can avoid
up to 68% of indolent Prostate Cancer
overdiagnosis will be solved!

11. MRI as part of AS represents a significant
advance in the oncological safety of the
AS protocol !!
Incorporation of MRI into surveillance protocols and decreasing the
intensity of repeat testing : cost-effective options !
Stratification with MRI and PSA-density
reduces unnecessary biopsy testing and
early termination of AS !

12. MRI first … but only after risk stratification
• Guidelines will be adapted, MRI as initial risk stratification tool in both
biopsy naive men and men with previous negative biopsy.
• Need standardisation, training of radiologists and capacity ( financial
sources)
• Suggested approach:
PSA
(ng/ml)
Age 50-59 % of men Age 60-70 % of men
< 1.0 Postpone re-testing at
least 5 years
50% Stop further testing 30%
1.0-3.0 Test with 2 to 4 yr
interval
40% Test with 2 to 4 yr interval 45%
>= 3.0 Reflex testing 10% Reflex testing 25%

13. NNI in comparison
Breast cancer
screening 1
Colorectal
cancer
screening 1
PSA-based
Prostate cancer
screening 2
Person years 800,000 800,000 825,018
Mortality Screening arm
(per 100,000 pers years)
26 60 43
Mortality Control arm
(per 100,000 pers years)
42 70 54
Cancer deaths (S-arm) 208 480 355
Cancer deaths (C-arm) 336 560 545
Relative Risk 0.61 (0.45-0.82) 0.85 (0.74-0.98) 0.79 (0.69-0.91)
NNS 1968 2175 781
NNT 18 29 27
Risk-based
1 based on the results from published randomised controlled trials of screening for breast cancer and colorectal cancer, for hypothetical
populations of 100000. Richardson et al J Med Screening 2001
2 based on ERSPC. Schröder et al. Lancet 2014

14. What is going on in daily clinical practice?

15. Conclusions
• Combination is key!
• PSA is a highly useful biomarker to start with
• Reflex testing is next step
• MRI is here to stay !
• Before MRI proper risk stratification is mandatory!
• With coordinated screening we will be able to
• maintain (improve) the prostate cancer mortality reduction
• and avoid harms (unnecessary testing and overdiagnosis (MRI based follow-up)
and uncertainty, anxiety and costs!