Download Alexander Liede,1 Oliver Günther,2 Brian Bennett,3 and Steven

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Prevalence of Non-metastatic Castration-Resistant Prostate Cancer in Europe
Alexander Liede, Oliver Günther, Brian Bennett, and Steven Wong
1
Model Assumptions and Source Data
• The model estimated prevalent patients within each clinical state at a specific point in
time using a dynamic patient flow model to accurately represent how tumors progress,
go into remission, recur, and respond to multiple courses of therapy (Figures 1 & 2).
– Patients could enter a specific state (“inflow”) as the result of either newly diagnosed
cancer, recurrence, or progression (Figure 2).
– The model also accounts for all-cause mortality (“outflow”) associated with each state
over time. Recurrence or progression represent outflows from clinical states, including
presence/absence of clinically detectable metastatic disease, prior treatment, and
castration-sensitive and CRPC phases (during ADT treatment).
– In this model, patients could only move forward from state to state, and could not move
backward into a previous state.
• The model uses a 19-year simulation initiating in 2008, using annual PC incidence
and distribution across the stage at diagnosis.
• The fundamentals of the model are described by Verdecchia et al (2002)10 for estimation
and projections of cancer prevalence from cancer registry data. Prevalence is estimated
from the modeled incidence and survival estimates and approximates the
limited-duration prevalence that would be recorded in a cancer registry.
– Relative survival estimates are derived directly from incidence and follow-up data and
population life tables, using standard survival analysis methods.
– All incident cases of PC recorded by country-level cancer registry (or GLOBOCAN1 if
country-level data were not available or not current), are allocated to cells within a
two-dimensional matrix defined by age at the index date and the number of years
passed since diagnosis (duration). Limited-duration prevalence is the resulting sum of
numbers from corresponding index date and duration combinations. Limited-duration
prevalence is also segmented by duration, by age cohort, and by stage.
Incidence
• All annual incidence rates were obtained directly from population-based national
cancer registries:
– l’Institut de veille sanitaire/l’Institut national du cancer (France)11
– Robert Koch Institut (Germany)12
– Istituto superiore di sanità (Italy)13
– GLOBOCAN 2002, 2008 (Spain, EU-5)1,14
– Cancer Research U.K.15
– and Austrian National Cancer Register16
• The model assumes that diagnosis rates will have stabilized during the projection
period and will not continue to grow.
• Age-adjusted incidence rates in 2010 are generated for each country (Table 1). The
model assumes that these age-specific PC incidence rates will not continue to
increase and will remain constant through the projection period, with age
demographics driving growth in incidence.17
Table 1. Age-adjusted PC
Incidence Rates in Each
EU-5 Country, 2010 and
2026 (per 100,000 Males
in the Population)
France
Germany
Italy
Spain
U.K.
2010
227.4
159.6
133.7
116.7
126.0
2026
286.4
209.3
167.6
151.5
150.1
PSA Levels/Tumor Burden
Limited data: Literature (U.S.) or
IMS Oncology Analyser™ (EU-5)
Metastasis
Treatment rates: Literature and IMS
Oncology Analyser™ (EU-5)
Androgen Deprivation Therapy (ADT)
Graph adapted from: Smith MR. Eur Urol Suppl 2009; 8(11): 821-838. *Data gaps in understanding of disease burden (prevalence) indicated.
Stage Distribution
• Stage distribution data from cancer registries demonstrate how increased PSA testing
in Europe has led to diagnosis of PC at earlier stages.
– Munich Cancer Registry integrated with recent Schleswig-Holstein registry data
(Germany)18,19
– Munich Cancer Registry (Germany) integrated with Stage IV data from literature
(France,20 Italy21 [no data for Spain, Italy data used])
– Northern Ireland Cancer Registry Cancer Services Audit (U.K.)22
ADT Treatment
• For country-specific inputs, IMS Oncology Analyser™ “evidence of ADT” data were
used.23
– IMS Oncology Analyser™ routinely captures data on patients treated by participating
physicians: from 2005 to 2011, there are up to 58,000 patients per year treated by
nearly 822 physicians in EU-5.23
– The model utilizes the average country-specific ADT rates, as reported for 17,842 M0
PC patients in EU-5 between January 1, 2005 and December 31, 2011.
Recurrence and Progression
• IMS Oncology Analyser™ data from 2005-2011 reveal country-level trends in
• Based on literature, the model assumed that 35% of patients with Stage
ADT in EU-5 (Figure 3).
I, II, and III disease have PSA relapses (estimates range from 12% to
• Overall, ADT rates from IMS Oncology Analyser™ for EU-5 are consistent with
59% in studies of newly diagnosed patients 5 to 15 years after radical
the “any ADT” rate of approximately 45% reported in the literature from U.S.
prostatectomy or radiotherapy).28,29
studies.24,25
– 44.8% in first year of diagnosis: 36% T1, 46% T2, and 76% T324
• This assumption is consistent with a recent study of PSA-level data from
– 43.2% in first year of diagnosis among T1 and T2 cases25
electronic medical records in the U.S., which found CRPC among 36%
of patients with M0 disease treated with ADT.
Survival
– Pirolli et al (2012)30 defined CRPC consistent with clinical trials using
• Historically, survival for patients with PC in Europe is lower than survival for
sequential rises in PSA (PSA1 < PSA2 < PSA3), with data on 1,818 men
patients in the U.S.
from 328 oncology and urology clinics in the U.S. with M0 PC and ≥ 1
• As diagnosis and treatment of PC in Europe have been improving compared to
PSA recorded during a 1-year period (March 2010 to March 2011) and
historical trends, survival in Europe will improve to the same extent as in the
recently treated with ADT for ≥ 6 months.
U.S.
• Accordingly, the model is based on country-specific survival data from
EUROCARE-4,26 adjusted to SEER survival curves or trends observed in the U.S.27
Figure 4. Five-Year Prevalence of PC During Projection Period, Based on Recent
Cancer Registry Data
60.0%
40.0%
20.0%
0.0%
EU-5
France
Germany
Italy
Spain
U.K.
2005
50.0%
37.5%
55.6%
27.3%
41.6%
73.6%
2006
47.9%
34.4%
45.2%
22.9%
47.1%
73.3%
1,200,000
1,000,000
100,000
800,000
80,000
400,000
200,000
0
EU-5
France
Germany
Italy
Spain
U.K.
2008
793,742
210,880
224,793
143,308
78,442
136,319
2010
911,161
258,591
258,063
154,271
93,524
146,711
2012
2014
2016
2018
2020
2022
2024
2026
973,145 1,012,641 1,054,885 1,097,035 1,137,975 1,179,383 1,221,401 1,263,952
284,755 298,947 314,819 330,280 344,443 357,855 370,683 383,159
274,212 283,198 292,400 301,919 311,707 321,919 332,300 342,691
160,080 165,850 171,739 177,612 183,437 189,515 195,896 202,586
101,614 106,104 111,034 116,041 121,098 126,621 132,795 139,598
152,484 158,542 164,892 171,184 177,291 183,472 189,727 195,918
600,000
40,000
200,000
20,000
EU-5
France
Germany
Italy
Spain
U.K.
2008
662,750
173,165
198,320
114,991
61,610
114,665
2010
768,274
215,232
229,275
124,993
74,579
124,195
2012
823,643
238,521
244,284
130,130
81,593
129,114
2014
858,272
250,971
252,431
135,216
85,426
134,228
2016
895,841
265,136
260,767
140,522
89,719
139,696
2018
933,233
278,976
269,317
145,782
94,067
145,090
2020
2022
969,281 1,005,728
291,626 303,645
278,041 287,154
150,935 156,295
98,407 103,119
150,273 155,516
2024
1,042,695
315,174
296,420
161,908
108,369
160,824
2026
1,080,111
326,398
305,699
167,781
114,148
166,085
41.2%
28.8%
40.0%
20.5%
49.3%
56.9%
300,000
250,000
200,000
150,000
• This model provides the first understanding of number of men living
in Europe with M0 CRPC.
• Although M0 CRPC represents a small subset of the overall PC
population (Figure 7), the model predicts an increase in the
prevalence of CRPC over the next 14 years.
• As men with M0 CRPC have an increased risk of developing
metastases (particularly to bone) resulting in a shortened lifespan,
these findings highlight the need for clinical trials to establish
standards of care for these patients, and for new therapeutic
options.
LIMITATIONS
100,000
50,000
274,212
244,284
22,017
Italy
160,080
130,130
6,288
Spain
101,614
81,593
9,548
U.K.
152,484
129,114
16,760
Austria
21,065
17,170
1,511
• The prevalence model is dependent on the accuracy and precision
of the source data (e.g., incidence data from population-based
cancer registries), which may decrease with each population
segment in the model, with great statistical variation driven by the
ADT assumptions.
• Further research is underway in 2012 to validate ADT rates for EU-5
(from IMS Oncology Analyser™), as well as to provide current data
on ADT rates in additional European countries.
1. Ferlay J et al. GLOBOCAN. 2008. http://globocan.iarc.fr, Lyon,
IARC, 2010.
2. Jemal A et al. CA Cancer J Clin. 2011; 61: 69-90.
3. Quinn M, Babb P. BJU Int. 2002; 90: 162-173.
4. Neppl-Huber C et al. Ann Oncol. 2012; 23(5): 1325-1334
(Epub 2011 Sep 28).
5. Kvåle R et al. J Natl Cancer Inst. 2007; 99: 1881-1887.
6. Shulman MJ, Benaim EA. J Urol. 2004; 172: 141-145.
7. Smith MR et al. J Clin Oncol. 2005; 23: 2918-2925.
8. Bubendorf L et al: Hum Pathol. 2000; 31: 578-583.
9. Sathiakumar N et al. PC Prostatic Dis. 2011; 14: 177-183.
10. Verdecchia A et al. Stat Med. 2002; 21: 3511-3526.
11. Institut national du cancer (INCa), Projections de l'incidence et
de la mortalité par cancer en France en. 2011,
http://www.invs.sante.fr, 2011.
12. Robert Koch Institut. Cancer in Germany. 2005/2006:
Incidence and Trends, http://www.rki.de, 2010.
13. Istituto superiore di sanità, AIRTUM database,
http://www.registri-tumori.it/, 2006.
14. Ferlay J et al. GLOBOCAN 2002. Lyon, IARC, 2004.
15. Cancer Research U.K., CancerStats,
http://info.cancerresearchuk.org/cancerstats/, 2011.
16. STATISTICS AUSTRIA, Austrian National Cancer Register (as
of 13 September 2011). Compiled on 10 October 2011.
2008
44.0%
35.9%
41.5%
25.1%
55.0%
54.7%
2009
46.3%
34.6%
44.9%
24.8%
57.3%
62.1%
2010
41.8%
33.4%
29.5%
22.0%
59.5%
53.3%
2011
41.6%
30.3%
20.4%
23.1%
63.5%
55.0%
2005-2011
44.8%
33.4%
41.6%
23.6%
52.3%
62.2%
60,000
400,000
0
2007
Figure 6. Five-Year Prevalence of M0 CRPC During Projection Period, Modeled
Using Country-Level IMS Oncology Analyser™ ADT Treatment Rates (see Figure 3)
120,000
Figure 7. Five-Year Prevalence of PC, M0 PC, and M0 CRPC in 2012, Modeled Using
Country-Level Rates From IMS Oncology Analyser™ (EU-5) or Literature Treatment Rates
With ADT (Austria)
284,755
238,521
18,001
80.0%
1,200,000
600,000
# CRPC
100.0%
1,400,000
800,000
35%
Figure 3. Trend Analysis of “Evidence of ADT” Among Patients with M0 PC Represented In
IMS Oncology Analyser™23
Figure 5. Five-Year Prevalence of M0 PC During Projection Period, Modeled From
Cancer Registry Data
1,000,000
# Treated with ADT
Recurrence and progression: Literature, 35%
PSA relapse rate applied to relapse curve (results
in19% to 25% range over projection period due
to increases in survival)
0
EU-5
France
Germany
Italy
Spain
U.K.
2008
48,576
10,971
14,908
4,486
6,032
12,178
2010
62,112
15,166
18,994
5,379
8,101
14,472
2012
72,613
18,001
22,017
6,288
9,548
16,760
2014
82,448
20,145
24,766
7,373
10,701
19,463
2016
89,810
21,930
26,709
8,145
11,615
21,411
2018
93,836
23,123
27,663
8,495
12,205
22,350
2020
98,136
24,345
28,768
8,861
12,858
23,305
2022
2024
2026
102,690 106,461 110,290
25,548 26,495 27,419
29,985 30,958 31,926
9,260
9,593
9,941
13,584 14,278 15,047
24,313 25,138 25,957
DISCLOSURES
REFERENCES
Germany
# Non-metastatic
Treatment rates: Literature, 45% “any ADT”,
consistent with 44.6% “evidence of ADT” per IMS
Oncology Analyser™ for Germany
Recurrence and progression:
Metastatic disease
# CRPC
CONCLUSIONS
PC
M0 PC
M0 CRPC
# Not treated
with ADT
# Treated with ADT
Recurrence and progression: Literature,
35% PSA relapse rate applied to relapse
curve (results in19% to 25% range over
projection period due to increases in
survival)
Time
France
Stage distribution: Stage IV metastatic data
from Munich Cancer Registry (Germany) integrated
with Stage IV data from literature (Italy, no data
available for Austria)
Metastatic
# Non-metastatic
81.5%
45%
CRPC
0
# Men living with
PC in 2012
Incidence: Austrian National Cancer Register
incidence rates applied to UN population projections
Mortality: Cancer registry, data
by stage and diagnosis year with
adjustment to recent trends
Survival: EUROCARE-4 survival data for Austria
with adjustment to recent trends in SEER
Stage distribution: Cancer registry,
non-metastatic (stage I-III, IV M0)
Start
of ADT
• For EU-5 countries, the model projects that
5-year prevalence of PC will increase from
approximately 1.0 million in 2012 to as high as
1.3 million in 2026 (Figure 4).
• M0 PC, which comprises about 85% of all PC
5-year prevalence, will increase from
approximately 0.8 million in 2012 to 1.1 million
by 2026 (Figure 5).
• M0 CRPC is projected to exceed 70,000 with a
projected increase to 110,000 patients by 2026
(Figure 6).
• In 2012, projected prevalence of M0 CRPC in
EU-5 is approximately 7% of the total PC
prevalence using “evidence of ADT” rates per
IMS Oncology Analyser™ in the M0 setting.
– Figure 7 summarizes estimates for EU-5 and
Austria using the same methodology, although
ADT rates for Austria are based on the
published literature (45%).
Inflow
Survival: Cancer registry, data by stage
and diagnosis year with adjustment to
recent trends
Prevalance not available*
RESULTS
Outflow
# Men living with
PC in 2012
Incidence: Cancer registry, new cases
from previous 5 years
B: Data Sources Contributing to Assumptions in Patient Flow Prevalence Model:
Austrian Example
Men
METHODS
PC
diagnosis
Inflow
Men
To estimate the prevalence of PC, M0 PC, and M0 CRPC by country in key European
countries (EU-5), and for each year from 2008 to 2026 (the projection period).
• Prevalence: 5-year limited-duration prevalence is provided and refers to the number
of men diagnosed with PC in the previous 5 years and alive on index date
(December 31) of projection year of interest.
• EU-5 countries: France, Germany, Italy, Spain, and United Kingdom (U.K.)
• To illustrate the model, data from Austria have been presented.
Cancer registry data:
Incidence, some prevalence1
A. Country-level Data “Inflows” and “Outflows” in the Patient Flow Prevalence Model by Population
Segment for 2012.
Castration-Resistant
Death
Castration-Sensitive
Men
STUDY OBJECTIVE
Figure 2. Disease States of Interest in Treatment Paradigm
Figure 1. Hypothetical Patient Diagnosed with M0 PC Illustrating States and Treatments Over Time
Coinciding with Elevated PSA Levels and Leading to Metastasis and Death*
Men
• Prostate cancer (PC) is the second most common cancer diagnosed among men,
with approximately 900,000 men diagnosed each year worldwide (13.8% of all cancer
incidence), and constitutes the third most common cause of cancer-related death in
men in developed countries.1,2
• In Europe, the incidence of reported PC has increased dramatically over the last two
decades as a result of widespread prostate-specific antigen (PSA) screening.3,4
Although the specific timing differs by country, mortality has declined in tandem with
increased incidence trends, and the vast majority of men present with localized disease
with no metastases.3-5
• During an initial hormone- or castration-sensitive phase, a rise in PSA levels can
occur after a variable time interval following primary surgical or radiation treatment,
prompting initiation of androgen-deprivation therapy (ADT) (Figure 1). ADT can
substantially control disease and decline serum PSA levels in almost all patients.6
• Although PCs are initially castration sensitive and respond to ADT,7 nearly all patients
progress to castration-resistant PC (CRPC), a disease state defined by rising PSA
levels during effective ADT in the absence of metastases.
• CRPC patients are at increased risk for developing clinically apparent metastatic
disease, particularly to bone.6,7 Patients with PC and bone metastases have a
significantly shortened lifespan compared with patients without metastases.8,9
Survival has been reported as 1 to 2 years.9
• Non-metastatic (M0) CRPC is a growing public health burden that has not been
adequately quantified.
• We report results of a model to estimate the prevalence of M0 CRPC in major
populations in Europe.
3
Center for Observational Research, Amgen Inc., Thousand Oaks, California, USA; 2Center for Observational Research, Amgen Ltd, Uxbridge, UK; 3Plan A Inc., Mountain View, California, USA
METHODS (Continued)
BACKGROUND
3
% ADT for Men with
M0 PC
1
2
17. United Nations, World Population Prospects: The 2010
Revision. 2011.
18. Munich Cancer Registry, Spezielle Auswertungen C61:
Prostatakarzinom, http://www.tumorregistermuenchen.de,
2010.
19. Rohde V et al. Urol Int. 2009, 83: 134-140.
20. Flamand V et al. Prog Urol. 2008; 18: 53-59.
21. Bono AV et al. Eur Urol. 1996; 30 Suppl 1: 2-6; discussion
19-21.
22. Gavin A et al. Cancer Services Audit. 1996 & 2001, Prostate,
2005.
23. IMS Oncology Analyzer™ analyses, IMS Health (and Amgen
Inc.), 2011-2012.
24. Gilbert SM et al. Urol Oncol. 2009; 29(6): 647-653
(Epub 2009 Nov 19).
25. Shahinian VB et al. N Engl J Med. 2010; 363: 1822-1832.
26. Istituto superiore di sanità, EUROCARE-4,
http://www.eurocare.it, 2009
27. Surveillance, Epidemiology, and End Results (SEER),
SEER*Stat Database: Incidence—SEER 9 Regs Research
Data, Nov 2010 Sub (1973–2008), www.seer.cancer.gov,
2011.
28. Pound CR et al. JAMA. 1999; 281: 1591-1597.
29. Amling CL et al. J Urol. 2000; 164: 101-105.
30. Pirolli M et al. J Clin Oncol (suppl). 2012; 30 (abstr 1581).
• This study was funded by Amgen Inc.
• Alex Liede and Oliver Günther are employees of Amgen Inc. and
have received stock or stock options.
• Brian Bennett and Steven Wong are consultants at Plan A.
ACKNOWLEDGEMENTS
• IMS Health provided analyses of IMS Oncology Analyser™ for
this study.
• We would like to thank Albert Y. Rhee, Amgen Inc. for
assistance with the poster.
European Society for Medical Oncology, Vienna, Austria; Sept 28 – Oct 2, 2012