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Frances Drummond National Cancer Registry, Ireland

What are the explanations for rising incidence and falling mortality in prostate cancer? An all-Ireland study. Frances Drummond National Cancer Registry, Ireland On behalf of the All-Ireland Prostate Cancer consortium. Background.

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Frances Drummond National Cancer Registry, Ireland

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  1. What are the explanations for rising incidence and falling mortality in prostate cancer? An all-Ireland study Frances Drummond National Cancer Registry, Ireland On behalf of the All-Ireland Prostate Cancer consortium

  2. 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

  3. Prostate cancer incidence and mortality Estimated incidence, Europe 2006 Ferlay J et al. Ann Oncol 2007; 18(3): 581-92

  4. Prostate cancer incidence and mortality Estimated incidence, Europe 2006 Estimated mortality, Europe 2006 Ferlay J et al. Ann Oncol 2007; 18(3): 581-92

  5. 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: • ERSPC reported a 20% decrease in prostate cancer mortality in the PSA screened group (2) • PLCO observed no difference between screened and unscreened groups (3) 1. McDavid 2004, Public Health Rep 119(2):174-186 2. Schroder F 2009, N Engl J Med;360:1320-8 3. Andriole G 2009, N Engl J Med;360:1310-9

  6. Comparing trends between countries have an important role to play in explaining incidence and mortality trends

  7. 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 delivery GPs “gate-keepers” to tertiary care Republic of Ireland (RoI): mixed public-private health system 50% have private health insurance €60 to visit GP/outpatient clinic in public system

  8. Comparing trends between countries have an important role to play in explaining incidence and mortality trends 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) Contrast in health services Northern Ireland (NI):publicly funded health care (NHS), free at the point of delivery GPs “gate-keepers” to tertiary care Republic of Ireland (RoI): mixed public-private health system 50% have private health insurance €60 to visit GP/outpatient clinic in public system 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

  9. Aim To investigate prostate cancer incidence and mortality trends and factors influencing these in the Republic of Ireland (RoI) and Northern Ireland (NI)

  10. Subjects and Methods

  11. 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)

  12. 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 • Information on PSA tests performed in NI since 1994 is routinely collected by the NICR • RoI • Data on all tests (1994-2005) were sought from the 36 laboratories which analyse PSA. • Used information from 2006 lab survey to estimate missing data (1). • We estimate that we collected information on 58% of the total tests, 94-05. • 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). • 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.

  13. Prostate biopsy data • RoI • 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. • Data on claims for all biopsies performed in private hospitals, by year and age group, VHI Healthcare and BUPA (1996 – 2005) • NI • Information on needle biopsies was obtained from the Directorate of Information Services which record procedure codes from all hospital discharges in NI (1999-2004). • Total counts were provided (these data could not be broken down by age).

  14. Prostate biopsy data • RoI • 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. • Data on claims for all biopsies performed in private hospitals, by year and age group, VHI Healthcare and BUPA (1996 – 2005) • NI • Information on needle biopsies was obtained from the Directorate of Information Services which record procedure codes from all hospital discharges in NI (1999-2004). • 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

  15. Statistical Analysis • Age-standardised rates (ASR) in men aged 50+ • incidence • mortality • PSA testing

  16. Statistical Analysis • Age-standardised rates (ASR) in men aged 50+ • incidence • mortality • PSA testing • Biopsy rates • crude rates for NI • rates for the RoI standardised to NI population

  17. Statistical Analysis • Age-standardised rates (ASR) in men aged 50+ • incidence • mortality • PSA testing • Biopsy rates • crude rates for NI • rates for RoI standardised to NI population • Annual Percentage Change (APC) • joinpoint regression: log-linear model • trends for all ages (50+) and by age-group (50-74, 75+)

  18. RESULTS

  19. Prostate cancer incidence rates, 1994-2005 • 19,844 prostate cancers in the RoI • 7,388 in prostate cancers in NI.

  20. Prostate cancer incidence rates, 1994-2005 All ages (≥50 years) • 19,844 prostate cancers in the RoI • 7,388 in prostate cancers in NI. APC and joinpoint segment

  21. Prostate cancer incidence rates, 1994-2005 All ages (≥50 years) • 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). APC and joinpoint segment

  22. Age-standardised incidence rates by age, 1994-2005 Ages 50-74 years APC and joinpoint segment * p-value<0.05

  23. Age-standardised incidence rates by age, 1994-2005 Ages 50-74 years Ages >75 years APC and joinpoint segment * p-value<0.05

  24. 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).

  25. 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 • RoI: 1994, 74 years; 2005, 68 years (p-trend<0.01); • NI: 1994, 74 years; 2005, 70 years (p-trend<0.01)).

  26. 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 • RoI: 1994, 74 years; 2005, 68 years (p-trend<0.01); • NI: 1994, 74 years; 2005, 70 years (p-trend<0.01)). Age at which Asymptomatic men are PSA tested by RoI and NI GPs

  27. Grade RoI NI

  28. Age-standardised rates PSA testing All ages (≥50 years) APC and joinpoint segment p<0.05 * p-value<0.05 Excludes tests performed in those with prostate cancer • 412 tests per 1,000 men ≥50 years in RoI, 2004 • 206 per 1,000 ≥50 years in 2004 in NI, 2004.

  29. Age-standardised rates PSA testing by age Ages 50-74, >75 years APC and joinpoint segment * p-value<0.05 Excludes tests performed in those with prostate cancer

  30. 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

  31. Prostate biopsy rates All men >50 years APC and joinpoint segment * p-value<0.05 Crude rates for NI; rates for RoI standardised to NI population

  32. Prostate biopsy rates All men >50 years Ages 50-74, >75 years, RoI APC and joinpoint segment APC and joinpoint segment * p-value<0.05 Crude rates for NI; rates for RoI standardised to NI population

  33. Age-standardised prostate cancer mortality rates

  34. Prostate cancer treatment % prostate cancer patients receiving radical prostatectomy and hormone therapy in 1996 Gavin A, 2005; Drummond F, 2007

  35. Prostate cancer treatment Treatment trends in RoI % prostate cancer patients receiving radical prostatectomy and hormone therapy in 1996 Gavin A, 2005; Drummond F, 2007

  36. Conclusions 1 • Prostate cancer Incidence was consistently higher in the RoI than NI

  37. 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

  38. 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 • lower median PSA level in those with cancer • studies among primary care physicians (Connolly, 2007 MD thesis; Drummond et al. BMC Fam Pract 2009) and urologists are consistent with this • consistent with differences in healthcare system

  39. 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 • lower median PSA level in those with cancer • studies among primary care physicians (Connolly, 2007 MD thesis; Drummond et al. BMC Fam Pract 2009) and urologists are consistent with this • consistent with differences in healthcare system • Information on PSA testing alone not sufficient to assess impact of screening activity on incidence – need biopsy information

  40. Conclusions 2 • PSA testing is not the reason for decreasing mortality rates in Ireland • mortality rates were falling from 1995 - before PSA testing became widespread • change in mortality essentially equivalent in the two countries – although PSA testing and biopsy rates much higher in RoI than NI

  41. Conclusions 2 • PSA testing is not the reason for decreasing mortality rates in Ireland • mortality rates were falling from 1995 - before PSA testing became widespread • change in mortality essentially equivalent in the two countries – although PSA testing and biopsy rates much higher in RoI than NI • Other possible explanations • changes in treatment (e.g. wide-spread use of hormonal therapy) • attribution bias

  42. All-Ireland Prostate Cancer Research Group National Cancer Registry Ireland Anne-Elie Carsin: statistician Harry Comber: director Frances Drummond: study co-ordinator Linda Sharp: epidemiologist Northern Ireland Cancer Registry/ Queen’s University Belfast Amanda Black: research fellow David Connolly: urologist Anna Gavin: registry director Liam Murray: epidemiologist Collaborators Erasmus University Medical Centre : Pim van Leeuwen International Agency for Research on Cancer: Philippe Autier Mathieu Boniol Lars Egevad

  43. 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: • NI Research & Development, • Health Research Board, • National Cancer Screening Service, • Irish College of General Practitioners

  44. Comparative study between the Republic of Ireland (RoI) and Northern Ireland (NI) 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 • National Cancer Registry Ireland • Cancer Prevention, National Cancer Institute • Erasmus University Medical Centre, Rotterdam, Netherlands • Cancer Epidemiology and Prevention Research Group, Queen's University Belfast • Department of Urology, Belfast City Hospital, Belfast, Northern Ireland • International Agency for Cancer Research, Lyon • Northern-Ireland Cancer Registry, Belfast

  45. Thank you !!!! f.drummond@ncri.ie

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