Active Surveillance for Prostate Cancer:

…when cancer fate is uncertain….

Brussels

16 september 2015

Chris Bangma

1 Disclosure

Men’s health concerns…

Active surveillance

What is it?

Why are we doing it?

When is it indicated?

What are the results?

Does it increase male life expectancy?

How can we make it better?

Can we do without Active Surveillance in Europe?

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What is Active Surveillance: statements

= “…avoiding an invasive therapy when you do not need it…”

= active monitoring of a low risk cancer, but invasive treament when signs of

cancer growth occur

Monitoring by e-supports of physicians and patients

Regular biopsies and blood sampling

For the younger man it delays, for the older it omits therapy

Why are we doing this? Indolent cancer

Some prostate cancers are

indolent:

They grow slowly

They metastasize late or

unnoticable

They may not harm you:

Because you have other

diseases that kill you before

you get metastases

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Indolent Prostate Cancer is frequent…

Autopsy data (Gosselaer, review 2005)

0

10

20

30

40

50

60

70

30-39

40-49

50-59

60-69

70-79

autopsy incidence

screening incidence

Sakr 1993

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How often does low risk prostate cancer occur? Higher incidence due to increased individual screening

In general population 30-40 % of cancers detected is indolent

(ERSPC)

75 % of men > 50 years in USA had their PSA, in Europe 40 %

In Europe 3.000.000 men with Pca, annually 300.000 diagnosed

So: in EU about 100.000 indolent tumours detected annually

When is Active Surveillance indicated?

1. When you have an low risk cancer by a reknown set of clinical

criteria

Biopsies-biomaterials-imaging

2. When you can manage regular checks

3. When you are fit to undergo a switch to curative therapy

4. When you are young enough to benefit from curative therapy

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PC specific and overall survival

0 5 10 150

20

40

60

80

100PC specific

Overall

Time after diagnosis (years)

Perc

en

t su

rviv

al

What is the outcome of low risk cancer?

Retrospective findings in screen-detected

low risk PCa (n = 616) (Sweden, Finland, Netherlands) (Eur Urol,2009)

How do you recognize low risk cancers?

Upfront:

Their histology: Grade 3+3=6

Their extend: low volume so small number of positive biopsies

Maybe by imaging (MRI) or genomic profiles

Later (reclassification):

Changes of histology

More positive repeat biopsies

Maybe larger on MRI imaging

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E-tool

1590 99

380

227

1 123

113 535 8

2 10

12

26 91 343

20

121

83 83 clinics in 17 EU-countries

>4500 participants

Wat may happen? the shift towards invasive treatment

N = 1481

After 2 years 73% on AS

Biopsy

Biopsy

Bul c.s. 2012

What is a good outcome?

True outcome is: a meta free survival, no cancer specific mortality, a

high quality of life

Surrogate outcome is: a shift towards a higher risk cancer, an

intervention, an altered biomarker

Progression is a NATURAL consequence of surveillance

Delayed treatment is NOT a failure: it is part of Active Surveillance

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Outcome of prospective studies on Active

Surveillance

Survival in the Toronto cohort (Klotz, AUA 2014)

N=840 men on AS

Shift to therapy if Gleason >4+3 or PSADT < 3 years

Median follow-up ca. 8 years

Overall survival 82%, 2 % death due to prostate cancer

Risk of metastases 4%

After 15 years 52 % remained untreated (dead or alive)

Actuarial 15 year Pca death is 6%, 20 year 14 %

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What are the results of long term Active Surveillance ?

Creating the worldwide Movember database…

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Does it increase male life expectancy?

NO: when there is no intervention, you just follow your natural

course as before…

…but it improves quality of life Less overtreatment

Less side effects

Less costs

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So what are the pitfalls?

Early reclassification (2-3 years), and need to shift to active therapy

Chance of missing progressive disease

Anxiety, lack of confidence

Costs?

For avoiding one treatment we can perform 15 years surveillance

For delaying 3 treatments we can avoid costs of 1 men with side

effects during that period

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How can we make it better?

Better selection at the start

Better reclassification methods to increase accuracy

Better predictions of individual life expectancy

Increase the level of confidence

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Can we do that in Europe?

YES as the PRIAS network to perform research is still gaining

popularity

YES as e-health is spreading

YES by joining forces between patient coalitions and medical

professionals to implement knowledge and tools

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Conclusions on Active Surveillance

Low risk prostate cancer is frequent due to individual screening

Active surveillance of low risk prostate cancer is unavoidable in order

to reduce overtreatment

Technological developments may select the best candidates to

improve current protocols

E-health brings all of this close to the patients that need it

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Imaging: MRI, Ultrasound

can it replace serial prostate biopsy ?*

1 in 3 men managed with AS have a more significant

cancer than thought on initial biopsy1

44% had disease predominantly in the anterior part of

the gland ( often under-sampled by TRUS biopsy)1

MRI targeted biopsy is as efficient at diagnosing sign.

PC as a 5 mm template biopsy2

1. Ayres BE et al. BJUI 2011 2. Kasivisvanathan V et al J Urol 2013

*Dr. C. Moore: Using mpMRI to replace serial biopsy in men on AS for PC:

presentation at AS conference Amsterdam

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