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Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)

Roobol, Monique J.; Kerkhof, Melissa; Schroeder, Fritz H.; Cuzick, Jack; Sasieni, Peter; Hakama, Matti; Stenman, Ulf Hakan; Ciatto, Stefano; Nelen, Vera and Kwiatkowski, Maciej, et al. (2009) In European Urology 56(4). p.584-591
Abstract
Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC.... (More)
Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (Cis) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of over diagnosis and overtreatment inherent in PCa screening. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved. (Less)
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keywords
Non compliance, Mortality reduction, Prostate cancer, Screening, Contamination, Adjusted analysis
in
European Urology
volume
56
issue
4
pages
584 - 591
publisher
Elsevier
external identifiers
  • wos:000270071700002
  • scopus:69249209651
ISSN
1873-7560
DOI
10.1016/j.eururo.2009.07.018
language
English
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yes
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a1cc05ff-15f9-4b8f-994c-dfc635c43836 (old id 1490065)
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2009-10-20 11:34:47
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2017-10-01 04:28:47
@article{a1cc05ff-15f9-4b8f-994c-dfc635c43836,
  abstract     = {Background: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. Objective: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. Design, setting, and participants: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162 243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). Intervention: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. Measurements: Relative risks (RRs) with 95% confidence intervals (Cis) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. Results and limitations: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. Conclusions: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of over diagnosis and overtreatment inherent in PCa screening. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.},
  author       = {Roobol, Monique J. and Kerkhof, Melissa and Schroeder, Fritz H. and Cuzick, Jack and Sasieni, Peter and Hakama, Matti and Stenman, Ulf Hakan and Ciatto, Stefano and Nelen, Vera and Kwiatkowski, Maciej and Lujan, Marcos and Lilja, Hans and Zappa, Marco and Denis, Louis and Recker, Franz and Berenguer, Antonio and Ruutu, Mirja and Kujala, Paula and Bangma, Chris H. and Aus, Gunnar and Tammela, Teuvo L. J. and Villers, Arnauld and Rebillard, Xavier and Moss, Sue M. and de Koning, Harry J. and Hugosson, Jonas and Auvinen, Anssi},
  issn         = {1873-7560},
  keyword      = {Non compliance,Mortality reduction,Prostate cancer,Screening,Contamination,Adjusted analysis},
  language     = {eng},
  number       = {4},
  pages        = {584--591},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC)},
  url          = {http://dx.doi.org/10.1016/j.eururo.2009.07.018},
  volume       = {56},
  year         = {2009},
}