title: What explains the differences between centres in the European screening trial? A simulation study.
abstract: The European Randomised study of Screening for Prostate Cancer (ERSPC) is a multicentre, randomised screening trial on men aged 55-69 years at baseline without known prostate cancer (PrCa) at randomisation to an intervention arm invited to screening or to a control arm. The ERSPC has shown a significant 21% reduction in PrCa mortality at 13 years of follow-up. The effect of screening appears to vary across centres, for which several explanations are possible. We set to assess if the apparent differences in PrCa mortality reduction between the centres can be explained by differences in screening protocols.
  
  
  
  We examined the centre differences by developing a simulation model and estimated how alternative screening protocols would have affected PrCa mortality.
  
  
  
  Our results showed outcomes similar to those observed, when the results by centres were reproduced by simulating the screening regimens with PSA threshold of 3 versus 4ng/ml, or screening interval of two versus four years. The findings suggest that the differences are only marginally attributable to the different screening protocols.
  
  
  
  The small screening impact in Finland was not explained by the differences in the screening protocols. A possible reason for it was the contamination of and the unexpectedly low PrCa mortality in the Finnish control arm.
authors.affiliation: University of Tampere, School of Health Sciences, Tampere, Finland. Electronic address: jaakko.nevalainen@uta.fi.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Nevalainen
authors.affiliation: Department of Clinical Chemistry, Helsinki University Central Hospital, Finland.
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
authors.affiliation: Tampere University Hospital, Department of Urology and University of Tampere, Medical School, Tampere, Finland.
authors.forename: Teuvo L
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Roobol
authors.affiliation: Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden; Memorial Sloan-Kettering Cancer Centre, Department of Surgery and Department of Epidemiology and Biostatistics, New York, NY, USA.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Carlsson
authors.affiliation: Finnish Cancer Registry, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Talala
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.affiliation: University of Tampere, School of Health Sciences, Tampere, Finland.
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
mesh_terms: D000368:Aged; D055088:Early Detection of Cancer / Q000379:methods*; D005060:Europe; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality
chemical_list: D017430:Prostate-Specific Antigen
keywords: Longitudinal PSA model; Prostate cancer; Prostate-specific antigen; Screening; Simulation model