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27/09/2019
1
Steven Joniau, MD, PhD
University Hospitals Leuven
Leuven
Belgium
Prostate Cancer Screening PCa essential epidemiology
Estimated Prostate cancer incidence & mortality worldwide 2018
https://gco.iarc.fr/today/fact-sheets-cancers
Estimated new cases and deaths in US, 2019
Siegel R, et al. CA Cancer J Clin 2019
PSA test
available
PCa incidence
Siegel R, et al. CA Cancer J Clin 2019
PSA test
available
Welch HG, et al. N Engl J Med, 2015
PCa metastasis, data from SEER
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PCa mortality
PCa death rate/ Period 1994-2012: annual decline of 3.7%
PSA test available
PSA test available
Siegel R, et al. CA Cancer J Clin 2016
Screening and Early Detection
CASE
John, 62-year old Caucasian man
Unremarkable past medical history
Never had a PSA test
Never had DRE
Mild LUTS (IPSS 5)
No family history of prostate, breast or ovarian cancer
Heard on the news about “a simple blood test that can
help diagnose prostate cancer”
Select the right answer
What is John’s life expectancy?
1. 15 years
2. 20 years
3. 25 years
4. 30 years
Select the right answer
What is John’s risk of having prostate cancer?
1. 10%
2. 20%
3. 30%
4. 40%
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High prevalence of undiagnosed PCa in
autopsy studies
Jahn JL, et al. Int J Cancer. 2014 Dec 29.
30%
SWOP – ERSPC risk calculator 1(WITHOUT PSA!)
http://www.prostatecancer-riskcalculator.com/seven-prostate-cancer-risk-calculators
8%
RISK OF POSITIVE BIOPSY
CASE (continued)
John, 62-year old Caucasian man
Unremarkable past medical history
Mild LUTS (IPSS 5)
No family history of prostate or breast cancer
John consents to PSA testing
His PSA is 3.2 ng/mL
Limited PSA elevation alone should not prompt immediate
biopsy
PSA level should be verified after a few weeks using the same
assay under standardized conditions in the same laboratory
Empiric use of antibiotics in an asymptomatic patient in order to
lower the PSA should not be undertaken
EAU Guidelines 2016
Prostate Biopsy
CASE (continued)
John, 62-year old Caucasian man
Unremarkable past medical history
Mild LUTS (IPSS 5)
No family history of prostate or breast cancer
His GP explains that PSA should be repeated after
some weeks.
His repeat PSA is 3.4 ng/mL
Select the right answer
With a PSA of 3.4 ng/mL, what is John’s risk of having
prostate cancer at random biopsies?
1. <10%
2. 10-20%
3. 20-30%
4. >30%
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“Ideal” marker for prostate cancerHEALTHY POPULATION + BENIGN PATHOLOGY
PROSTATE CANCER
100% Specificiteit 100% Gevoeligheid
0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 100.0
CI/E
LB/0
2/2
01
0/0
68
Cut off
PSA, ng/mL0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 100.0
Healthy / BPH
Cut off
PSA, ng/mL
Reality of the PSA test…
0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 100.0
Indolent PCa
Lethal PCa
Thompson IM. NEJM. 350(22):2239-46, 2004.
Prevalence of prostate cancer among men with a
prostate-specific antigen level ≤4.0 ng/mL PCPT risk calculator
17%
4%
Screening trials – PCa Screening in
Europe and USA
Screening and Prostate-Cancer Mortality in a Randomized European StudyFH Schröder et al. N Engl J Med 2009
N Engl J Med 2012Lancet 2014Eur Urol 2019
Mortality Results from a Randomized Prostate-Cancer Screening TrialGL Andriole et al. N Engl J Med 2009
JNCI 2012BJUI 2018
Hugosson J, et al. Eur Urol 2019
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Key Findings ERSPC – 9, 11, 13 & 16 years
Follow up NN to screen NN to diagnoseRelative Risk
Reduction
9 yrs 1410 48 15%
11 yrs 979 35 22%
13 yrs 742 26 21%
16 yrs 570 18 20%
• With extended follow-up, the mortality reduction remains unchanged
• Number needed to screen and to diagnose is decreasing (below the NNS in breast cancer trials)
PLCO Trial
Prostate cancer
Lung cancer
Colorectal cancer
Ovarian cancer
From 1993-2001, 76.693 men 55-74 years
were randomised in 10 centres in US
Screening vs. usual care (!)
Screening: yearly DRE and PSA for 6 years
Pinsky PF, et al. BJUI 2018
PLCO Trial
...no evidence of mortality benefit for organized annual
screening compared with opportunistic screening...
Shoag JE, et al. N Engl J Med, 2016
Problem: Contamination !
PSA testing every 2 yr with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml
Göteborg Randomized Population-Based
Screening Trial
42% lower PCa mortality in the organized
screening vs. the opportunistic testing arm
To avoid 1 PCa death:
139 men have to be screened
13 PCa’s have to be diagnosed
Godtman RA, et al. Eur Urol 2015
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Screening: EAU recommendations
Mottet N et al. EAU-ESTRO-ESUR-SIOG guidelines on prostate cancer. Available at: www.uroweb.org/guidelines
Do not subject men to PSA testing without counselling them on the
potential risks and benefits
Offer an individualised risk-adapted strategy for early detection to a
well-informed man with a good performance status and a life expectancy
≥10-15 years
Offer early PSA testing in well-informed men at elevated risk of having PCa:
• Men >50 years of age
• Men >45 years of age and a family history of PCa
• Men >45 years of age and African-American
Stop early diagnosis of PCa based on life expectancy and performance
status; men who have a life expectancy of <15 years are unlikely to benefit
EAU screening recommendationsRating
strength
Strong Weak
LE
3
3
2b
3
CASE (continued)
John, 62-year old Caucasian man
Unremarkable past medical history
Mild LUTS (IPSS 5)
No family history of prostate or breast cancer
His PSA is 3.4 ng/mL
His GP explains that a rectal exam may provide further
vital information regarding PCa risk
DRE shows mild BPH, no suspect nodules
DRERisk assessment: EAU recommendations
SWOP – ERSPC risk calculator 3 SWOP – ERSPC risk calculator 3
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Ultrasound-guided – standard of care
Cleansing enema ±
Stopping anticoagulants/antiaggregants ±
Oral or intravenous antibiotics (quinolones)
know resistance to quinolones in your institution
Prostate Biopsy
At least 8 systematic biopsies are recommended in a prostate of
about 30 cc
10 to 12 cores are recommended in larger volume prostates
Transition zone biopsies are not recommended and should be
limited to repeat biopsies
Periprostatic block
+
Separate containers
Additional cores from areas suspect by DRE or TRUS
EAU Guidelines Update 2019
Prostate Biopsy
Prostate Biopsy
EAU Guidelines Update 2019 Gleason DF. In: Tannenbaum M, ed. Urologic Pathology: The prostate, 1977
• If 2 grades are present, Gleasonscore = Sum of the most common (primary) and second most common (secondary) grade
• If 3 grades are present, Gleasonscore = Sum of the most common and the highest grade, irrespective of its extent
• In case only 1 grade is present, itneeds to be doubled to yield theGleason score
Gleason grade and score
Gleason grade and score
Gleason DF. In: Tannenbaum M, ed. Urologic Pathology: The prostate, 1977
• If 2 grades are present, Gleasonscore = Sum of the most common (primary) and second most common (secondary) grade
• If 3 grades are present, Gleasonscore = Sum of the most common and the highest grade, irrespective of its extent
• In case only 1 grade is present, itneeds to be doubled to yield theGleason score
Grading: Gleason score and ISUP grade
ISUP
grade
Gleason
score
Histological characteristics
1 2-6 Only individual discrete well-formed glands
2 7 (3+4) Predominantly well-formed glands with lesser
component of poorly-formed/fused/cribriform
glands
3 7 (4+3) Predominantly poorly-formed/fused/cribriform
glands with lesser component of well-formed
glands*
4 8 (4+4,
3+5 or 5+3)
Only poorly-formed/fused/cribriform glands OR
Predominantly well-formed glands with lesser
component lacking glands** OR
Predominantly lacking glands and lesser
component of well-formed glands**
5 9-10 Lacks gland formation (or with necrosis) with or
without poorly formed/fused/cribriform glands*
Epstein JI et al. Am J Surg Pathol 2016;40:244-52
*For cases with >95% poorly-formed/fused/cribriform glands or lack of glands on a core or at RP, the component
of <5% well-formed glands is not factored into the grade**Poorly-formed/fused/cribriform glands can be a more minor component
ISUP: International Society of Urological Pathology; RP: radical prostatectomy
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mpMRI
MR targeted biopsies
Moore C. et al. Eur Urol 64 (2014) 544-552
• Visual registration: cognitive fusion
• Software registration: MRI/TRUS fusion
• Direct in-bore biopsies
EAU guidelines for imaging today
Staging: TNM system
Brierly JD et al. TNM classification of malignant tumors. UICC International Union Against Cancer. 8th Ed, 2017
Mottet N et al. EAU-ESTRO-ESUR-SIOG guidelines on prostate cancer.
Primary Tumour (T)
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Clinically unapparent tumour that is not palpable
T1a: Tumour incidental histological finding in ≤5% of tissue resectedT1b: Tumour incidental histological finding in >5% of tissue resected
T1c: Tumour identified by needle biopsy (e.g. because of elevated PSA)
T2 Tumour that is palpable and confined within prostate
T2a: Tumour involves ≤50% of one lobeT2b: Tumour involves >50% of one lobe but not both lobes
T2c: Tumour involves both lobes
T3 Tumour extends through the prostate capsule*
T3a: Extracapsular extension (unilateral or bilateral) including microscopic
bladder neck involvement
T3b: Tumour involves seminal vesicle(s)
T4 Tumour is fixed or invades adjacent structures other than seminal vesicles,
such as external sphincter, rectum, bladder, levator muscles, and/or pelvic
wall
Regional Nodes (N)
NX Regional lymph nodes
were not assessed
N0 No regional lymph node
metastases
N1 Metastasis in regional
lymph node(s)
Distant Metastases (M)
M0 No distant metastases
M1 Distant metastases
M1a: Non-regional
lymph node(s)
M1b: Bone(s)
M1c: Other site(s) with
or without bone
disease
*Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2
Risk stratification of PCa
Mottet N et al. EAU-ESTRO-ESUR-SIOG guidelines on prostate cancer. Available at: www.uroweb.org/guidelines
Localised PCaLocally
advanced PCa
Low
Risk
Intermediate
RiskHigh
Risk
PSA <10 ng/ml
and
Gleason score <7
(ISUP grade 1)
and
cT1a-2a
PSA 10-20 ng/ml
or
Gleason score 7
(ISUP grade 2/3)
or
cT2b
PSA >20 ng/ml
or
Gleason score >7
(ISUP grade 4/5)
or
cT2c
Any PSA
Any Gleason score
(any ISUP grade)
cT3-4 or cN+
10%
20%
40%
Who dies of prostate cancer?
Rider JR et al. Eur Urol 2012
All ages <65 years 65-75 years >75 years
Prostate cancer Cardiovascular Other
Low
risk
Inte
rme
dia
teri
skH
igh
ris
k
Natural evolution of non-curatively treated PCa
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Natural evolution of non-curatively treated PCa
Low risk High riskIntermediate risk
PCa population
Control population
Rider JR et al. Eur Urol 2012Rider JR et al. Eur Urol 2012
QUESTIONS ???
How can we solve the problems of
overdiagnosis and overtreatment?
First PSA test at age 45-49
Vickers A et al. BMJ 2013
10% of men with the highest PSA areresponsible for 44% of PCa deaths!
Vickers A et al. BMJ 2013
First PSA test at age 45-49
Lifetime risk of clinically diagnosed PCa or PCametastases based on a PSA at age 60
Vickers A J et al. BMJ 2010;341John