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Prostate Cancer in 2009, part I. Now and the future!
Why we have ‘Active surveillance, its purpose, its outcome and other matters.
Monique J. Roobol, PhD, MSc
Overview
The facts of prostate cancer
Screening for prostate cancer
Tumor characteristics over time
Management of prostate cancer
Active Surveillance
Risk indicator
The facts of prostate cancer
0
10
20
30
40
5060
70
30-39
40-49
50-59
60-69
70-79
autopsyincidence
Sakr 1993
The facts of prostate cancer
42
9.5 2.90
5
10
15
20
25
30
35
40
45 Microscopic PC
Clinical PC
Deathly PC
Is PC always a life threatening disease?
The facts of prostate cancer
The diagnosis of low risk prostate cancer is increasing
‘90 ‘92 ‘94 ‘96 ‘98 ‘00
20
40
60
80
100
0
Cooperberg et al, J Urol 2003
The facts of prostate cancer
Cancer death by type of cancer and age, The Netherlands, 2000www.CBS.nl
Cancer mortality increases strongly from 50 years of age onwards, peaking at ages 75-79 years.
Prostate cancer is an important health problem.
The facts of prostate cancer
Conclusions:
1.Prostate cancer is a major health problem
2.Death from prostate cancer and/or metastatic prostate cancer should
be avoided
3.The majority of detectable prostate cancer cases do not give any
complaints or will lead to death
Early detection of especially those prostate cancer cases
that cause symptoms and/or are life threatening is desirable
Overview
The facts of prostate cancer
Screening for prostate cancer
Tumor characteristics over time
Management of prostate cancer
Active Surveillance
Risk indicator
Screening for prostate cancer
Belgium 10.359
Finland 80.379
France 85.414
Italy 14.977
Netherlands 42.376
Spain 4.278
Sweden 19.911
Switzerland 10.307
Total 268.001
www.erspc.org
Screening for prostate cancer
21.166 men in control arm
??
??
?
?
?
42.376 men
21.210 men in screening arm
PSA
DRE
TRUS
Prostate biopsy
Prostate cancer
Death of prostate cancer
Prostate cancer
9.176
2.241933
?
? ??
?
?
Screening for prostate cancer
With applying a relatively non aggressive screening algorithm,
i.e PSA cut-off value >= 3.0 ng/ml
Sextant prostate biopsy
a 4 year screening interval
The number of screen detected PC cancers is already more than twice
as high as compared to the clinical setting
Conclusion: Screening results in a considerable increase of the
incidence of PC
Question: Selective for potentially life threatening PC?
Overview
The facts of prostate cancer
Screening for prostate cancer
Tumor characteristics over time
Management of prostate cancer
Active Surveillance
Risk indicator
Tumor characteristics over time
Screen detected PC, initial screening
76% of T1C cases has Gleason score 6
Screen detected PC, repeat screenings
87% of T1C cases has Gleason score 6
Percentage of potentially indolent PC increases
ERSPC, Rotterdam ( 1993-2009)
Tumor characteristics over time
59% of t1C cases has Gleason score 6
Percentage of potentially indolent PC increases, also in the clinical setting
ERSPC, Rotterdam ( 1993-2009) , PC detected in control arm
Tumor characteristics over time
PSA use in the clinical setting is increasing and subsequently
also the clinical detection of potentially indolent PC.
PSA based screening is becoming more and more common and
is not selective for potentially life threatening prostate cancer
Overview
The facts of prostate cancer
Screening for prostate cancer
Tumor characteristics over time
Management of prostate cancer
Active Surveillance
Risk indicator
Management of prostate cancer
Albertsen tables JAMA ‘05
N=767
Clinical stage ≤ T2
Palliative treatment
Dark grey = PCa †
Light grey = nonPCa †
White = survival
Remember: app 60% of cases had Gleason score <= 6
Much more die with PC than of PC
Management of prostate cancer
ERSPC Rotterdam 1994 – 2002, age 55 – 67, interval 4 years Leadtime
(y) Overdiagnosis
(%) T1 13.2 69 T2 9.3 38 T3+ 8.0 30 Gleason < 7 12.2 62 Gleason 7 9.9 40 Gleason > 7 4.0 8
Management of prostate cancer
Management of prostate cancer
Hormones SurgeryRadio Ther. AS
PC cases detected within ERSPC Rotterdam.
Clinical stage T1C or T2A.
Active treatment in app. 70% of the cases
Overview
The facts of prostate cancer
Screening for prostate cancer
Tumor characteristics over time
Management of prostate cancer
Active Surveillance
Risk Indicator
Active Surveillance
‘primum non nocere’ ("First, not to harm." )
In the case of prostate cancer :
Cure might not be possible in those whom it is needed…
… but cure may not be needed in those whom it is possible…
(Whitmore 1988)
Active Surveillance
Overdiagnosis would not matter if treatment had no adverse effects.
It would be acceptable to treat all cases, including those destined never to cause
symptoms.
However, while radical treatment for
prostate cancer may or may not improve
a man’s longevity, it can certainly have
a big impact on his lifestyle.
Ideally, such intervention should
be restricted to those who need it.
Active Surveillance
Aims to individualise the management of PC by offering curative
treatment in those cases with evidence of biochemical or
histological progression.
Watchful waiting, a policy of observation with the use of palliative treatment for symptomatic progression.
I would have been here sooner
Active Surveillance
Prostate Cancer Research International: Active Surveillance
Spin off from the European Randomized Study of Screening for
Prostate Cancer (ERSPC)
Initiative of the Department of Urology of the Erasmus Medical Centre
Based on available literature
Prospective study design, ongoing evaluation, aid in decision making
Main goal is to reduce over treatment
It also provides an ideal setting for research to identify new markers,
which, in the future, could improve our ability to determine which men
need, and which men do not need, treatment for their prostate cancer.
Web based study, accessible for urologists all over the world
Active Surveillance
Active Surveillance
Inclusion criteria:
PSA 10
PSA density <0,2
T2
Gleason 3+3=6
2 positive biopsies
Active Surveillance
Follow-up criteria:
PSA doubling time (DT) >3 yr
T2
Gleason 3+3=6
2 positive biopsies
If PSA >20: Bonescan
If PSA DT 3-10 yr: Yearly rebiopsies
Active Surveillance
Timetable:
PSA (1x / 3 mo) (1x / 6 after na 2 yr)
DRE (1x / 6 mo) (1x / 12 mo after 2 yr)
Rebiopsies (standard after 1, 4 and 7 yr)
Active Surveillance
Active surveillance
Baseline characteristics (N=500)
Active Surveillance
PSA-DT and rebiopsy findings
Active Surveillance
Deferred active therapies and reasons for treatment change
Active Surveillance
Anxiety and distress during active surveillance (N=129)
Management of prostate cancer
Outcomes of PC eligible for Active Surveillance who were managedexpectantly (ERSPC, N=616)Van den Bergh et al. Eur urol 2008.
PSA < 10.0 ng/mlPSA-density <0.2 ng/ml per mlStage T1C/T2Gleason score 3 + 3 = 6<= 2 positive biopsy cores
Management of prostate cancer
The calculated (Kaplan-Meier) 10-yr PCa-specific survival was 100%,
which sharply contrasted with 77% overall survival. Men still alive
showed favourable PSA characteristics.
The calculated 10-yr treatment-free survival was only 43%, objective
signs of progression often did not indicate the shift to radical treatment.
Conclusions: AS seems justified in selected men. Prospective
protocolbased AS programs are necessary to optimise selection criteria
and to find the appropriate trigger points for switching to active therapy.
Follow-up regimen and preliminary results (Klotz et al 2007, Choo et al 2002)
Visits every 3 months for 2 years, later 6 monthly, PSA, DRE, one
biopsy month 18
Active treatment: either PSADT < 2 years (later < 3 years), upgrade
biopsy or clinical progression
331 men, follow-up 5.8 years, 34% are off surveillance
15% had PSA progression
3% clinical progression
4% histological progression
3 patients died of PC after treatment (99% DSS) at 7 year follow-up
Follow-up regimen and preliminary results (Carter et al 2007)
Biannual visits, annual biopsy (>= 12 core), PSA and DRE
Active treatment: biopsy decisive, Gleason pattern 4 or 5, > 2 cores+,
more than 50% PC in one core, PSA change no trigger
407 men, follow-up 3-4 years, 103 (25%) treated
10/49 treated by RP (20%) potentially non curable
Active Surveillance
Make the PRIAS website accessible for more (European) countries
Inclusion based on nomogram use?
Inclusion and/or follow-up based on new biomarkers?
Establishment of biorepository ( PROCABIO)
Individual active surveillance protocol, depending on comorbidity and
age?
Quality of Life on long term?
Is delay in radical treatment dangerous? ( evaluations ongoing)
Costs?
PRIAS will be a important source of information with respect to
application and safety of active surveillance
Overview
The facts of prostate cancer
Screening for prostate cancer
Tumor characteristics over time
Management of prostate cancer
Active Surveillance
Risk Indicator
Prostate Cancer Risk Indicator
A decision aid for lay men and urologist to help them in the question
prostate cancer screening yes or no
www.urosource.com
Gives balanced information on pro’s and con’s
Gives risk estimates on having a biopsy detectable prostate cancer on
5 different levels
Gives risk estimate on potentially indolent prostate cancer
Validated for understanding and effect.
PRIAS, THE study for Active Surveillance
Questions ? Interested in future participation ?
Protocol and PIF’s can be translated into own language
(Europa Uomo)
Always acces to own data
Participation in scientific research
www.prias-project.org