Transcript Document

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
70
60
50
40
30
20
10
0
autopsy
incidence
30- 40- 50- 60- 7039 49 59 69 79
Sakr 1993
The facts of prostate cancer
45
Microscopic PC
40
Clinical PC
Deathly PC
35
42
30
25
20
15
10
5
9.5
2.9
0
Is PC always a life threatening disease?
The facts of prostate cancer
100
Cooperberg et al, J Urol 2003
80
60
40
20
0
‘90
‘92
‘94
‘96
‘98
‘00
The diagnosis of low risk prostate cancer is increasing
The facts of prostate cancer
Cancer death by type of cancer and age,
The Netherlands, 2000
www.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
Sweden
19.911
Switzerland
10.307
Total
www.erspc.org
4.278
268.001
Screening for prostate cancer
42.376 men
21.166 men in control
arm
21.210 men in screening
arm
?
?
?
?
?
Prostate cancer
933
?
?
?
?
?
Prostate cancer
2.241
PSA
Death of prostate
cancer
Prostate biopsy
DRE
9.176
TRUS
?
??
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
Screen detected PC, repeat screenings
76% of T1C cases has Gleason score 6
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
T1
T2
T3+
Gleason < 7
Gleason 7
Gleason > 7
Leadtime Overdiagnosis
(y)
(%)
13.2
69
9.3
38
8.0
30
12.2
9.9
4.0
62
40
8
Management of prostate cancer
Management of prostate cancer
PC cases detected
within ERSPC
Rotterdam.
Clinical stage T1C
or T2A.
Active treatment in
app. 70% of the
cases
Hormones
Radio Ther.
Surgery
AS
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.
I would have been here sooner
Watchful waiting, a policy of observation
with the use of palliative treatment for
symptomatic progression.
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
PSA < 10.0 ng/ml
PSA-density <0.2 ng/ml per ml
Stage T1C/T2
Gleason score 3 + 3 = 6
<= 2 positive biopsy cores
Outcomes of PC eligible for Active Surveillance who were managed
expectantly (ERSPC, N=616)
Van den Bergh et al. Eur urol 2008.
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
 [email protected]
 [email protected]