Alex Tsodikov, PhD; Roman Gulati, MS; Eveline A.M. Heijnsdijk, PhD; Paul F. Pinsky, PhD; Sue M. Moss, PhD; Sheng Qiu, MS; Tiago M. de Carvalho, MS; Jonas Hugosson, MD; Christine D. Berg, MD; Anssi Auvinen, MD; Gerald L. Andriole, MD; Monique J. Roobol, PhD; E. David Crawford, MD; Vera Nelen, MD; Maciej Kwiatkowski, MD; Marco Zappa, PhD; Marcos Luján, MD; Arnauld Villers, MD; Eric J. Feuer, PhD; Harry J. de Koning, MD; Angela B. Mariotto, PhD; Ruth Etzioni, PhD
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.
Grant Support: By National Cancer Institute Award number U01CA157224.
Disclosures: Dr. Moss reports grants from the Prostate Cancer Research Foundation and the European Association of Urology during the conduct of the study. Dr. Auvinen reports personal fees from EPID Research and MSD outside the submitted work. Dr. Kwiatkowski reports personal fees from Myriad, Astellas, and Janssen outside the submitted work. Dr. Luján reports a grant from Fondo de Investigación Sanitaria during the conduct of the study. Dr. Etzioni reports personal fees from GRAIL outside the submitted work and ownership of equity in Seno. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2586.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Not available. Statistical code: Source code or runs using the FHCRC model are available from Mr. Gulati (e-mail, email@example.com), runs using the MISCAN model are available from Dr. Heijnsdijk (e-mail, firstname.lastname@example.org), and source code or runs using the UMICH model are available from Dr. Tsodikov (e-mail, email@example.com). Data set: PLCO data are available from the National Cancer Institute Cancer Data Access System (https://biometry.nci.nih.gov/cdas). ERSPC data may be available from Dr. Moss (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Ruth Etzioni, PhD, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M2-B230, PO Box 19024, Seattle, WA 98109; e-mail, email@example.com.
Current Author Addresses: Dr. Tsodikov and Mr. Qiu: Department of Biostatistics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109-2029.
Mr. Gulati and Dr. Etzioni: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024.
Drs. Heijnsdijk and de Koning and Mr. de Carvalho: Department of Public Health, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
Dr. Pinsky: Division of Cancer Prevention, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD 20892.
Dr. Moss: Wolfson Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Dr. Hugosson: Department of Urology, Sahlgrenska University Hospital, Blå stråket 5, 413 45 Göteborg, Sweden.
Dr. Berg: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, 401 North Broadway, Baltimore, MD 21231.
Dr. Auvinen: School of Health Sciences, PL 100 33014 University of Tampere, Finland.
Dr. Andriole: Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, 4921 Parkview Place, St. Louis, MO 63110.
Dr. Roobol: Department of Urology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
Dr. Crawford: Urologic Oncology, University of Colorado, 1665 Aurora Court, Aurora, CO 80045.
Dr. Nelen: Provinciaal Instituut voor Hygiëne, Kronenburgstraat 45, 2000 Antwerpen, Belgium.
Dr. Kwiatkowski: Department of Urology, Kantonsspital Aarau, CH5001 Aarau, Switzerland.
Dr. Zappa: Unit of Epidemiology, Institute for Cancer Prevention, Via delle Oblate 2, 50141, Florence, Italy.
Dr. Luján: Servicio de Urología, Hospital Universitario Infanta Cristina, Universidad Complutense de Madrid, Avenida Nueve de Junio n° 2, Parla, 28981 Madrid, Spain.
Dr. Villers: Department of Urology, CHU Lille, Université de Lille, F-59000 Lille, France.
Drs. Feuer and Mariotto: Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD 20892.
Author Contributions: Conception and design: A. Tsodikov, R. Gulati, J. Hugosson, E.D. Crawford, A. Villers, E.J. Feuer, H.J. de Koning, R. Etzioni.
Analysis and interpretation of the data: A. Tsodikov, R. Gulati, E.A.M. Heijnsdijk, P.F. Pinsky, S. Qiu, C.D. Berg, A. Auvinen, G.L. Andriole, M. Zappa, A. Villers, H.J. de Koning, A.B. Mariotto, R. Etzioni.
Drafting of the article: A. Tsodikov, R. Gulati, E.D. Crawford, H.J. de Koning, R. Etzioni.
Critical revision of the article for important intellectual content: A. Tsodikov, R. Gulati, E.A.M. Heijnsdijk, P.F. Pinsky, S.M. Moss, T.M. de Carvalho, C.D. Berg, A. Auvinen, G.L. Andriole, M.J. Roobol, M. Kwiatkowski, A. Villers, E.J. Feuer, H.J. de Koning, R. Etzioni.
Final approval of the article: A. Tsodikov, R. Gulati, E.A.M. Heijnsdijk, P.F. Pinsky, S.M. Moss, S. Qiu, T.M. de Carvalho, J. Hugosson, C.D. Berg, A. Auvinen, G.L. Andriole, M.J. Roobol, E.D. Crawford, V. Nelen, M. Kwiatkowski, M. Zappa, M. Luján, A. Villers, E.J. Feuer, H.J. de Koning, A.B. Mariotto, R. Etzioni.
Provision of study materials or patients: J. Hugosson, G.L. Andriole, E.D. Crawford, M. Luján, A. Villers, H.J. de Koning.
Statistical expertise: A. Tsodikov, R. Gulati, P.F. Pinsky, S. Qiu, E.J. Feuer, R. Etzioni.
Obtaining of funding: A. Tsodikov, G.L. Andriole, M. Luján, A. Villers, H.J. de Koning, A.B. Mariotto, R. Etzioni.
Administrative, technical, or logistic support: A. Tsodikov, R. Gulati, C.D. Berg, E.J. Feuer, A.B. Mariotto.
Collection and assembly of data: A. Tsodikov, R. Gulati, P.F. Pinsky, S.M. Moss, S. Qiu, J. Hugosson, C.D. Berg, A. Auvinen, G.L. Andriole, M.J. Roobol, E.D. Crawford, V. Nelen, M. Kwiatkowski, H.J. de Koning, A.B. Mariotto.
The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction.
To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO.
Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models.
Randomized controlled trials in Europe and the United States.
Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization.
Prostate cancer screening.
Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began.
Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P = 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P = 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening.
The MLT is a simple metric of screening and diagnostic work-up.
After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality.
National Cancer Institute.
Tsodikov A, Gulati R, Heijnsdijk EA, et al. Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials. Ann Intern Med. [Epub ahead of print 5 September 2017]167:449–455. doi: 10.7326/M16-2586
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Published: Ann Intern Med. 2017;167(7):449-455.
Published at www.annals.org on 5 September 2017
Hematology/Oncology, Prostate Cancer.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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