Carlotta Buzzoni1, Anssi Auvinen2, Monique J Roobol3, Sigrid Carlsson4, Sue M Moss5, Donella Puliti1, Harry J de Koning6, Chris H Bangma3, Louis J Denis7, Maciej Kwiatkowski8, Marcos Lujan9, Vera Nelen10, Alvaro Paez11, Marco Randazzo12, Xavier Rebillard13, Teuvo L J Tammela14, Arnauld Villers15, Jonas Hugosson16, Fritz H Schröder3, Marco Zappa17. 1. Clinical and Descriptive Epidemiology and Registries Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy. 2. School of Health Sciences, University of Tampere, Tampere, Finland. 3. Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands. 4. Department of Urology, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 5. Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. 6. Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands. 7. Oncological Centre Antwerp, Belgium. 8. Department of Urology, Kantonsspital Aarau, Aarau, Switzerland; Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany. 9. Urology Department, Hospital Infanta Cristina, Parla, Madrid, Spain. 10. Provinciaal Instituut voor Hygiene, Antwerp, Belgium. 11. Department of Urology, Hospital Universitario de Fuenlabrada, Madrid, Spain. 12. Department of Urology, Kantonsspital Aarau, Aarau, Switzerland; Department of Urology University Hospital Zürich, Zürich, Switzerland. 13. Department of Urology, Clinique BeauSoleil - EA2415, Montpellier, France. 14. Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland. 15. Department of Urology, CHU Lille, Univ Lille Nord de France, Lille, France. 16. Department of Urology, Sahlgrenska Academy at University of Gothenburg, Sweden. 17. Clinical and Descriptive Epidemiology and Registries Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy. Electronic address: m.zappa@ispo.toscana.it.
Abstract
BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality. DESIGN, SETTING, AND PARTICIPANTS: Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis. RESULTS AND LIMITATIONS: In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03-2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16-1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89-1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52-0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller. CONCLUSIONS: The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr. PATIENT SUMMARY: The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer.
RCT Entities:
BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality. DESIGN, SETTING, AND PARTICIPANTS: Information on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis. RESULTS AND LIMITATIONS: In the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03-2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16-1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89-1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52-0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller. CONCLUSIONS: The results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr. PATIENT SUMMARY: The findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer.
Authors: F H Schröder; L J Denis; M Roobol; V Nelen; A Auvinen; T Tammela; A Villers; X Rebillard; S Ciatto; M Zappa; A Berenguer; A Paez; J Hugosson; P Lodding; F Recker; M Kwiatkowski; W J Kirkels Journal: BJU Int Date: 2003-12 Impact factor: 5.588
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Authors: Pim J van Leeuwen; Ries Kranse; Timo Hakulinen; Jonas Hugosson; Teuvo L Tammela; Stefano Ciattoy; Monique J Roobol; Marco Zappa; Harry J de Koning; Chris H Bangma; Sue M Moss; Anssi Auvinen; Fritz H Schröder Journal: J Med Screen Date: 2013-03 Impact factor: 2.136
Authors: Randi F Fonager; Helle D Zacho; Niels C Langkilde; Joan Fledelius; June A Ejlersen; Christian Haarmark; Helle W Hendel; Mine Benedicte Lange; Mads R Jochumsen; Jesper C Mortensen; Lars J Petersen Journal: Am J Nucl Med Mol Imaging Date: 2017-11-01
Authors: Leonard P Bokhorst; Marco Zappa; Sigrid V Carlsson; Maciej Kwiatkowski; Louis Denis; Alvaro Paez; Jonas Hugosson; Sue Moss; Anssi Auvinen; Monique J Roobol Journal: BJU Int Date: 2016-05-20 Impact factor: 5.588
Authors: Adrien N Bernstein; Jonathan E Shoag; Ron Golan; Joshua A Halpern; Edward M Schaeffer; Wei-Chun Hsu; Paul L Nguyen; Art Sedrakyan; Ronald C Chen; Scott E Eggener; Jim C Hu Journal: J Urol Date: 2017-12-26 Impact factor: 7.450