bvro / abro teaching course on prostate cancer

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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


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


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


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)



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)



Mild LUTS (IPSS 5)


His GP explains that PSA should be repeated after

some weeks.

His repeat PSA is 3.4 ng/mL


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)



Mild LUTS (IPSS 5)


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

bvro / abro teaching course on prostate cancer

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