Prostate Cancer Towards an Optimal Interval for Prostate Cancer Screening Pim J. van Leeuwen a, *, Monique J. Roobol a , Ries Kranse b , Marco Zappa c , Sigrid Carlsson d , Meelan Bul a , Xiaoye Zhu a , Chris H. Bangma a , Fritz H. Schro ¨der a , Jonas Hugosson d a Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands; b Dutch Cancer Registry (IKNL), Rotterdam, The Netherlands; c Unit of Clinical Epidemiology, Institute for Study and Prevention of Cancer, Florence, Italy; d Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Go ¨teborg, Sweden EUROPEAN UROLOGY 61 (2012) 171–176 available at www.sciencedirect.com journal homepage: www.europeanurology.com Article info Article history: Accepted August 2, 2011 Published online ahead of print on August 10, 2011 Keywords: Prostate cancer Screening PSA Interval Early detection Abstract Background: The rate of decrease in advanced cancers is an estimate for determining prostate cancer (PCa) screening program effectiveness. Objective: Assess the effectiveness of PCa screening programs using a 2- or 4-yr screening interval. Design, setting, and participants: Men aged 55–64 yr were participants at two centers of the European Randomized Study of Screening for Prostate Cancer: Gothenburg, Sweden (2-yr screening interval, n = 4202), and Rotterdam, the Netherlands (4-yr screening interval, n = 13 301). We followed participants until the date of PCa, the date of death, or the last follow-up at December 31, 2008, or up to a maximum of 12 yr after initial screening. Potentially life-threatening (advanced) cancer was defined as cancer with at least one of following characteristics: clinical stage T3a, M1, or N1; serum prostate- specific antigen (PSA) >20.0 ng/ml; or Gleason score 8 at biopsy. Intervention: We compared the proportional total (advanced) cancer incidence (screen- detected and interval cases), defined as the ratio of the observed number of (advanced) cancers to the expected numbers of (advanced) cancers based on the control arm of the study. Measurements: The proportional cancer incidence from the second screening round until the end of observation was compared using a 2- or 4-yr screening interval. Results and limitations: From screening round 2 until the end of observation, the proportional cancer incidence was 3.64 in Gothenburg and 3.08 in Rotterdam (relative risk [RR]: 1.18; 95% confidence interval [CI], 1.04–1.33; p = 0.009). The proportional advanced cancer incidence was 0.40 in Gothenburg and 0.69 in Rotterdam (RR: 0.57; 95% CI, 0.33–0.99; p = 0.048); the RR for detection of low-risk PCa was 1.46 (95% CI, 1.25–1.71; p < 0.001). This study was limited by the assumption that PSA testing in the control arm was similar in both centers. Conclusions: A 2-yr screening interval significantly reduced the incidence of advanced PCa; however, the 2-yr interval increased the overall risk of being diagnosed with (low- risk) PCa compared with a 4-yr interval in men aged 55–64 yr. Individualized screening algorithms must be improved to provide the strategy for this issue. # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Erasmus MC, University Medical Center, Room NH 227, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Tel. +31 10 703 2242; Fax: +31 10 703 5315. E-mail address: p.vanleeuwen@erasmusmc.nl (P.J. van Leeuwen). 0302-2838/$ – see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2011.08.002