Post on 04-Feb-2016
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What are the explanations for rising incidence and falling mortality in prostate cancer? An all-Ireland studyFrances Drummond
National Cancer Registry, Ireland
On behalf of the All-Ireland Prostate Cancer consortium
Background
Prostate cancer is the most commonly diagnosed cancer in men in the US and Europe
Incidence has increased significantly in the last 20+ years
A major cause of cancer death - third in Ireland
Mortality is decreasing in most high income countries
Prostate cancer incidence and mortality
Ferlay J et al. Ann Oncol 2007; 18(3): 581-92
Estimated incidence, Europe 2006
Prostate cancer incidence and mortality
Ferlay J et al. Ann Oncol 2007; 18(3): 581-92
Estimated incidence, Europe 2006 Estimated mortality, Europe 2006
Prostate Specific Antigen (PSA) Prostate Specific Antigen (PSA), a biomarker
PSA testing has contributed to the increase in incidence(1)
Whether PSA testing decreases mortality is heavily debated
Randomized trials did not consistently show mortality decreases associated with prostate specific antigen (PSA) testing:o ERSPC reported a 20% decrease in prostate cancer mortality in the PSA
screened group (2)o PLCO observed no difference between screened and unscreened groups (3)
1. McDavid 2004, Public Health Rep 119(2):174-1862. Schroder F 2009, N Engl J Med;360:1320-83. Andriole G 2009, N Engl J Med;360:1310-9
Comparing trends between countries have an important role to play in explaining incidence and mortality trends
Comparing trends between countries have an important role to play in explaining incidence and mortality trends
Contrast in health services
Northern Ireland (NI): publicly funded health care (NHS), free at the point of deliveryGPs “gate-keepers” to tertiary care
Republic of Ireland (RoI): mixed public-private health system50% have private health insurance€60 to visit GP/outpatient clinic in public system
Contrast in PSA testing practices/policies
Northern Ireland (NI): PSA “screening” not recommended in primary care (NHS Cancer Screening, PCRMP)
but, PSA testing going on (1)
Republic of Ireland (RoI): No guidelines; NCF recommend against pop-based screening (2006)
PSA testing widespread in primary care (2)Major variations in practice (3)
Comparing trends between countries have an important role to play in explaining incidence and mortality trends
1. Gavin A, 2004 BJU Int, 3. Drummond FJ 2008 Ir J Med Sci. 2008 Dec;177(4):317-23.
2. Drummond FJ 2009 BMC Fam Pract 12;10:3
Contrast in health services
Northern Ireland (NI): publicly funded health care (NHS), free at the point of deliveryGPs “gate-keepers” to tertiary care
Republic of Ireland (RoI): mixed public-private health system50% have private health insurance€60 to visit GP/outpatient clinic in public system
Aim
To investigate prostate cancer incidence and mortality trends and factors influencing these in the Republic of Ireland (RoI) and Northern Ireland (NI)
Subjects and Methods
Prostate cancer incidence Data on invasive prostate cancers (ICD-O2:C61) were obtained from the
National Cancer Registry Ireland (NCRI) (1994-2005) and the Northern Ireland Cancer Registry (NICR) (1993-2005)
Prostate cancer incidence Data on invasive prostate cancers (ICD-O2:C61) were obtained from the
National Cancer Registry Ireland (NCRI) (1994-2005) and the Northern Ireland Cancer Registry (NICR) (1993-2005)
PSA NI
o Information on PSA tests performed in NI since 1994 is routinely collected by the NICR
RoIo Data on all tests (1994-2005) were sought from the 36 laboratories which
analyse PSA. o Used information from 2006 lab survey to estimate missing data (1).o We estimate that we collected information on 58% of the total tests, 94-05.o Data on PSA tests were linked to the NCRI database by name, DOB and
address (where available). A similar linkage was performed in NI (2). o PSA tests performed after the date of diagnosis with cancer were excluded.
1. Drummond FJ 2008 Ir J Med Sci. 2008 Dec;177(4):317-23.
2. Connolly D, 2008 Cancer Epidemiol Biomarkers Prev;17(2):271-8.
Prostate biopsy data RoI
o Numbers of prostatic biopsies (ICD9 60.11-60.15), by year and age-group, were obtained from the Hospital In-Patient Enquiry System (HIPE) - records all discharges from all public hospitals (1994-2005.
o Data on claims for all biopsies performed in private hospitals, by year and age group, VHI Healthcare and BUPA (1996 – 2005)
NIo Information on needle biopsies was obtained from the Directorate of
Information Services which record procedure codes from all hospital discharges in NI (1999-2004).
o Total counts were provided (these data could not be broken down by age).
Prostate biopsy data RoI
o Numbers of prostatic biopsies (ICD9 60.11-60.15), by year and age-group, were obtained from the Hospital In-Patient Enquiry System (HIPE) - records all discharges from all public hospitals (1994-2005.
o Data on claims for all biopsies performed in private hospitals, by year and age group, VHI Healthcare and BUPA (1996 – 2005)
NIo Information on needle biopsies was obtained from the Directorate of
Information Services which record procedure codes from all hospital discharges in NI (1999-2004).
o Total counts were provided (these data could not be broken down by age).
Prostate cancer mortality data Mortality data were extracted from World Health Organization mortality
database for the period 1979-2006
Statistical Analysis
Age-standardised rates (ASR) in men aged 50+o incidenceo mortalityo PSA testing
Statistical Analysis
Age-standardised rates (ASR) in men aged 50+o incidenceo mortalityo PSA testing
Biopsy rateso crude rates for NIo rates for the RoI standardised to NI population
Statistical Analysis
Age-standardised rates (ASR) in men aged 50+o incidenceo mortalityo PSA testing
Biopsy rateso crude rates for NIo rates for RoI standardised to NI population
Annual Percentage Change (APC)o joinpoint regression: log-linear modelo trends for all ages (50+) and by age-group (50-74, 75+)
RESULTS
Prostate cancer incidence rates, 1994-2005
19,844 prostate cancers in the RoI
7,388 in prostate cancers in NI.
Prostate cancer incidence rates, 1994-2005
19,844 prostate cancers in the RoI
7,388 in prostate cancers in NI.
segment start end APC
RoI 1994-2005 226 485 7.3 *
NI 1994-1999 216 212 -0.41999-2003 212 307 9.7
2003-2005 307 300 -1.1
ASR
0
100
200
300
400
500
600
Stan
dard
ised-
rate
per
100
,000
APC and joinpoint segment
All ages (≥50 years)
Prostate cancer incidence rates, 1994-2005
19,844 prostate cancers in the RoI
7,388 in prostate cancers in NI.
Age-standardised incidence rate (1994-2005) was on average 41% higher in the RoI (346 per 100,000 men aged >50 years) than in NI
(245 per 100,000 men aged >50). segment start end APC
RoI 1994-2005 226 485 7.3 *
NI 1994-1999 216 212 -0.41999-2003 212 307 9.7
2003-2005 307 300 -1.1
ASR
0
100
200
300
400
500
600
Stan
dard
ised-
rate
per
100
,000
APC and joinpoint segment
All ages (≥50 years)
Age-standardised incidence rates by age, 1994-2005
segment APC segment APC
RoI 1994-2005 10.9 * 1994-2002 2.8 *2002-2005 -7.3 *
NI 1994-1997 -4.0 1994-2005 -2.1 *
1997-2003 13.3 *
2003-2005 2.7
50-74 years 75+
0
200
400
600
800
1000
Stand
ardise
d-rate
per 1
00,00
0
APC and joinpoint segment
Ages 50-74 years
* p-value<0.05
Age-standardised incidence rates by age, 1994-2005
segment APC segment APC
RoI 1994-2005 10.9 * 1994-2002 2.8 *2002-2005 -7.3 *
NI 1994-1997 -4.0 1994-2005 -2.1 *
1997-2003 13.3 *
2003-2005 2.7
50-74 years 75+
0
200
400
600
800
1000
Stand
ardise
d-rate
per 1
00,00
0
APC and joinpoint segment
Ages 50-74 years Ages >75 years
0
200
400
600
800
1000
Stand
ardise
d-rate
per 1
00,00
0
* p-value<0.05
Age at diagnosis
The median age at cancer diagnosis was significantly lower in the RoI (71 years) compare to NI (73 years) (p<0.01).
Age at diagnosis
The median age at cancer diagnosis was significantly lower in the RoI (71 years) compare to NI (73 years) (p<0.01).
Median age decreased significantly over time o RoI: 1994, 74 years; 2005, 68
years (p-trend<0.01); o NI: 1994, 74 years; 2005, 70 years
(p-trend<0.01)).
Age at diagnosis
0
10
20
30
40
50
60
<50 50-59 >70
Age (years) %
tota
l bas
elin
e te
sts
RoI
NI
Age at which Asymptomatic men are PSA tested by RoI and NI GPs
The median age at cancer diagnosis was significantly lower in the RoI (71 years) compare to NI (73 years) (p<0.01).
Median age decreased significantly over time o RoI: 1994, 74 years; 2005, 68
years (p-trend<0.01); o NI: 1994, 74 years; 2005, 70 years
(p-trend<0.01)).
Grade
Segment APC
RoI Low 1994-2005 +10.9
High 1994-2005 +2.7
No Grade 1994-2002 +7.3
2002-2005 -13.8
NI Low 1994-1997 -2.3
1997-2003 +14.3
2003-2005 0.0
High 1994-2000 -1.1
2000-2005 +17.0
No Grade 1994-2005 -6.2
RoI NI
Age-standardised rates PSA testing
0
100
200
300
400
500
600
1994
1996
1998
2000
2002
2004
Age
stan
dard
ised
Rat
e pe
r 1,0
00
412 tests per 1,000 men ≥50 years in RoI, 2004
206 per 1,000 ≥50 years in 2004 in NI, 2004.
p<0.05
APC and joinpoint segment
* p-value<0.05Excludes tests performed in those with prostate cancer
segment start end APC
RoI 1994-2004 51 412 23.3 *
NI 1994-2004 82 206 9.7 *
ASR
All ages (≥50 years)
Age-standardised rates PSA testing by age
0
100
200
300
400
500
600
1994
1996
1998
2000
2002
2004
Age
stan
dard
ised
Rat
e pe
r 1,0
00 APC and joinpoint segment
segment APC segment APC
RoI 1994-2004 25.2 * 1994-2004 16.1 *
NI 1994-2004 10.6 * 1994-1996 55.6 *
1996-2004 4.0 *
50-74 years 75+
* p-value<0.05Excludes tests performed in those with prostate cancer
Ages 50-74, >75 years
Median PSA level in tests within 6 months prior to cancer diagnosis
Data from 7,208 (36% of the prostate cancer cases 1994-2005) in the RoI and 4,592 (66% of the prostate cancer cases 1994-2005)
*P<0.001
94-96
Median (IQR)
97-99
Median (IQR)
00-02
Median (IQR)
03-05
Median (IQR)
P-trend
All >50 RoI 31 (10-53)* 21 (10-50)* 17 (8-47)* 12 (7-28)* <0.01
NI 52 (20-153)* 38 (14-119)* 25 (11-65)* 17 (9-45)* <0.01
50-74 RoI 27 (8-50)* 16 (8-48)* 13 (7-29)* 10 (6-19)* <0.01
NI 45 (17-147)* 31 (12-94)* 20 (10-48)* 13 (8-32)* <0.01
>75 RoI 43 (13-66)* 35 (14-63)* 30 (14-82) 27 (13-79) 0.160
NI 56 (23-163)* 43 (16-149)* 39 (16-101) 31 (16-80) <0.01
Prostate biopsy rates
0
100
200
300
400
500
600
700
800
Cru
de r
ate
s p
er
100,0
00
RoINI
All men >50 years
APC and joinpoint segment
segment start end APC
RoI 1996-2004 258 709 13.5 *
NI 1999-2004 152 532 28.5 *
ASR
* p-value<0.05
Crude rates for NI; rates for RoI standardised to NI population
Prostate biopsy rates
0
100
200
300
400
500
600
700
800
Cru
de r
ate
s p
er
100,0
00
RoINI
All men >50 years
APC and joinpoint segment
segment start end APC
RoI 1996-2004 258 709 13.5 *
NI 1999-2004 152 532 28.5 *
ASR
* p-value<0.05
Crude rates for NI; rates for RoI standardised to NI population
0
100
200
300
400
500
600
700
800
Rate
s p
er
100,0
00
50-7475+
Ages 50-74, >75 years, RoI
segment APC segment APC
RoI 1996-2004 15.3 * 1996-1999 25.7 *
50-74 years 75+
APC and joinpoint segment
Age-standardised prostate cancer mortality rates
segment APC segment APC segment APC
RoI 1979-1995 2.6 * 1979-1995 2.0 * 1979-1996 2.8 *
1995-2006 -1.5 * 1995-2006 -3.1 * 1996-2006 -0.9
NI 1979-1995 1.9 * 1979-1990 2.8 * 1979-1998 2.1 *
1995-2006 -1.3 1990-2006 -1.5 * 1998-2006 -1.8
50-74 years 75+All ages (50+)
Prostate cancer treatment
NI RoI
Radical prostatectomy 1% 5%
Hormone therapy 68% 40%
% prostate cancer patients receiving radical prostatectomy and hormone therapy in 1996
Gavin A, 2005; Drummond F, 2007
Prostate cancer treatment
NI RoI
Radical prostatectomy 1% 5%
Hormone therapy 68% 40%
% prostate cancer patients receiving radical prostatectomy and hormone therapy in 1996
Gavin A, 2005; Drummond F, 2007 0%
10%
20%
30%
40%
50%
60%
70%
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006%
pro
stat
e ca
ncer
trea
ted
any surgery radiotherapy chemo
hormone other surgery radical
Treatment trends in RoI
Conclusions 1 Prostate cancer Incidence was consistently higher in the RoI than NI
Conclusions 1 Prostate cancer Incidence was consistently higher in the RoI than NI The difference in incidence mainly due to the relative intensity of cancer
investigation via prostatic biopsy, rather than PSA testing
Conclusions 1 Prostate cancer Incidence was consistently higher in the RoI than NI The difference in incidence mainly due to the relative intensity of cancer
investigation via prostatic biopsy, rather than PSA testing 1994-2000, PSA rates similar, but incidence higher in the RoI PSA testing was increasingly used in NI before 1999, but no rise in incidence
until 1999 very low biopsy rate in NI in 1999; incidence rose as biopsy rate rose higher biopsy rate in the RoI – and higher incidence in RoI, age-specific trends in incidence mirror those for biopsies evidence that threshold for biopsy lower in RoI
o lower median PSA level in those with cancero studies among primary care physicians (Connolly, 2007 MD thesis; Drummond et al. BMC
Fam Pract 2009) and urologists are consistent with this o consistent with differences in healthcare system
Conclusions 1 Prostate cancer Incidence was consistently higher in the RoI than NI The difference in incidence mainly due to the relative intensity of cancer
investigation via prostatic biopsy, rather than PSA testing 1994-2000, PSA rates similar, but incidence higher in the RoI PSA testing was increasingly used in NI before 1999, but no rise in incidence
until 1999 very low biopsy rate in NI in 1999; incidence rose as biopsy rate rose higher biopsy rate in the RoI – and higher incidence in RoI, age-specific trends in incidence mirror those for biopsies evidence that threshold for biopsy lower in RoI
o lower median PSA level in those with cancero studies among primary care physicians (Connolly, 2007 MD thesis; Drummond et al. BMC
Fam Pract 2009) and urologists are consistent with this o consistent with differences in healthcare system
Information on PSA testing alone not sufficient to assess impact of screening activity on incidence – need biopsy information
Conclusions 2 PSA testing is not the reason for decreasing
mortality rates in Irelando mortality rates were falling from 1995 - before PSA testing
became widespreado change in mortality essentially equivalent in the two
countries – although PSA testing and biopsy rates much higher in RoI than NI
Conclusions 2 PSA testing is not the reason for decreasing
mortality rates in Irelando mortality rates were falling from 1995 - before PSA testing
became widespreado change in mortality essentially equivalent in the two
countries – although PSA testing and biopsy rates much higher in RoI than NI
Other possible explanationso changes in treatment (e.g. wide-spread use of hormonal
therapy) o attribution bias
All-Ireland Prostate Cancer Research Group
National Cancer Registry Ireland
Anne-Elie Carsin: statisticianHarry Comber: directorFrances Drummond: study co-
ordinatorLinda Sharp: epidemiologist
Northern Ireland Cancer Registry/Queen’s University Belfast
Amanda Black: research fellowDavid Connolly: urologistAnna Gavin: registry
directorLiam Murray: epidemiologist
CollaboratorsErasmus University Medical Centre : Pim van LeeuwenInternational Agency for Research on Cancer: Philippe Autier
Mathieu BoniolLars Egevad
Acknowledgments
laboratories who provided data on PSA tests HIPE, VHI and BUPA who provided biopsy data GPs, Urologists and radiologists for completing questionnaires those at the NICR and NCRI for collecting and processing the data and
reviewing death certificates Funded by:
o NI Research & Development, o Health Research Board, o National Cancer Screening Service, o Irish College of General Practitioners
Comparative study between the Republic of Ireland (RoI) and Northern Ireland (NI)
1. National Cancer Registry Ireland2. Cancer Prevention, National Cancer Institute3. Erasmus University Medical Centre, Rotterdam, Netherlands4. Cancer Epidemiology and Prevention Research Group, Queen's University Belfast5. Department of Urology, Belfast City Hospital, Belfast, Northern Ireland6. International Agency for Cancer Research, Lyon7. Northern-Ireland Cancer Registry, Belfast
A-E Carsin1, FJ Drummond1, A Black2, PJ van Leeuwen3, L Sharp1, LJ Murray4, D Connolly5, L Egevad6, M Boniol6,
P Autier6, H Comber1, A Gavin7
Thank you !!!!
f.drummond@ncri.ie