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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?
2
3
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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