frances drummond national cancer registry, ireland

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


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)


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



Biopsy rateso crude rates for NIo rates for the RoI standardised to NI population



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.




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 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



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


Ages 50-74 years

* p-value<0.05

Age-standardised incidence rates by age, 1994-2005


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


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


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


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


* p-value<0.05Excludes tests performed in those with prostate cancer


RoI 1994-2004 51 412 23.3 *

NI 1994-2004 82 206 9.7 *

ASR


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


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



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



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


RoI 1996-2004 15.3 * 1996-1999 25.7 *

50-74 years 75+


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


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


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 !!!!

[email protected]

frances drummond national cancer registry, ireland

Documents

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