title: Metastatic Prostate Cancer Incidence and Prostate-specific Antigen Testing: New Insights from the European Randomized Study of Screening for Prostate Cancer.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  RESULTS
  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: Clinical and Descriptive Epidemiology and Registries Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy.
authors: Carlotta
authors: C
authors: Buzzoni
authors: School of Health Sciences, University of Tampere, Tampere, Finland.
authors: Anssi
authors: A
authors: Auvinen
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Monique J
authors: MJ
authors: Roobol
authors: Department of Urology, Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Surgery (Urology Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Sigrid
authors: S
authors: Carlsson
authors: Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors: Sue M
authors: SM
authors: Moss
authors: Clinical and Descriptive Epidemiology and Registries Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy.
authors: Donella
authors: D
authors: Puliti
authors: Department of Public Health, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors: Harry J
authors: HJ
authors: de Koning
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Chris H
authors: CH
authors: Bangma
authors: Oncological Centre Antwerp, Belgium.
authors: Louis J
authors: LJ
authors: Denis
authors: Department of Urology, Kantonsspital Aarau, Aarau, Switzerland; Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany.
authors: Maciej
authors: M
authors: Kwiatkowski
authors: Urology Department, Hospital Infanta Cristina, Parla, Madrid, Spain.
authors: Marcos
authors: M
authors: Lujan
authors: Provinciaal Instituut voor Hygiene, Antwerp, Belgium.
authors: Vera
authors: V
authors: Nelen
authors: Department of Urology, Hospital Universitario de Fuenlabrada, Madrid, Spain.
authors: Alvaro
authors: A
authors: Paez
authors: Department of Urology, Kantonsspital Aarau, Aarau, Switzerland; Department of Urology University Hospital Zürich, Zürich, Switzerland.
authors: Marco
authors: M
authors: Randazzo
authors: Department of Urology, Clinique BeauSoleil - EA2415, Montpellier, France.
authors: Xavier
authors: X
authors: Rebillard
authors: Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
authors: Teuvo L J
authors: TL
authors: Tammela
authors: Department of Urology, CHU Lille, Univ Lille Nord de France, Lille, France.
authors: Arnauld
authors: A
authors: Villers
authors: Department of Urology, Sahlgrenska Academy at University of Gothenburg, Sweden.
authors: Jonas
authors: J
authors: Hugosson
authors: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Fritz H
authors: FH
authors: Schröder
authors: Clinical and Descriptive Epidemiology and Registries Unit, ISPO - Cancer Research and Prevention Institute, Florence, Italy. Electronic address: m.zappa@ispo.toscana.it.
authors: Marco
authors: M
authors: Zappa
mesh_terms: D000368:Aged; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D015994:Incidence; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D012044:Regression Analysis; D018570:Risk Assessment
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Metastatic cancer incidence; Mortality reduction; PSA; Prostate screening