The long-term effects of sigmoidoscopy screening on colorectal cancer (CRC) incidence and mortality in women and men are unclear.
To determine the effectiveness of flexible sigmoidoscopy screening after 15 years of follow-up in women and men.
Randomized controlled trial. (ClinicalTrials.gov: NCT00119912)
Oslo and Telemark County, Norway.
Adults aged 50 to 64 years at baseline without prior CRC.
Screening (between 1999 and 2001) with flexible sigmoidoscopy with and without additional fecal blood testing versus no screening. Participants with positive screening results were offered colonoscopy.
Age-adjusted CRC incidence and mortality stratified by sex.
Of 98 678 persons, 20 552 were randomly assigned to screening and 78 126 to no screening. Adherence rates were 64.7% in women and 61.4% in men. Median follow-up was 14.8 years. The absolute risks for CRC in women were 1.86% in the screening group and 2.05% in the control group (risk difference, −0.19 percentage point [95% CI, −0.49 to 0.11 percentage point]; HR, 0.92 [CI, 0.79 to 1.07]). In men, the corresponding risks were 1.72% and 2.50%, respectively (risk difference, −0.78 percentage point [CI, −1.08 to −0.48 percentage points]; hazard ratio [HR], 0.66 [CI, 0.57 to 0.78]) (P for heterogeneity = 0.004). The absolute risks for death from CRC in women were 0.60% in the screening group and 0.59% in the control group (risk difference, 0.01 percentage point [CI, −0.16 to 0.18 percentage point]; HR, 1.01 [CI, 0.77 to 1.33]). The corresponding risks for death from CRC in men were 0.49% and 0.81%, respectively (risk difference, −0.33 percentage point [CI, −0.49 to −0.16 percentage point]; HR, 0.63 [CI, 0.47 to 0.83]) (P for heterogeneity = 0.014).
Follow-up through national registries.
Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women.
Primary Funding Source:
Norwegian government and Norwegian Cancer Society.
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Author, Article, and Disclosure Information
Sørlandet Hospital Kristiansand, Kristiansand, Norway, and University of Oslo Institute of Health and Society and Oslo University Hospital, Oslo, Norway (Ø.H., M.L., M.B., T.J.E.)
University of Oslo Institute of Health and Society and Oslo University Hospital, Oslo, Norway, and Harvard T.H. Chan School of Public Health and Harvard–MIT Division of Health Sciences and Technology, Boston, Massachusetts (M.K., M.A.H.)
Harvard T.H. Chan School of Public Health and Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts; University of Oslo Institute of Health and Society, Oslo, Norway (E.A.)
Oslo University Hospital, Oslo, Norway; orwegian University of Science and Technology, Trondheim, Norway (E.S.)
University of Bergen Surgical Research Laboratory, Bergen, Norway (J.L.)
Umeå University Clinical Pharmacology Unit, Umeå, Sweden (J.S.)
Oslo University Hospital and University of Oslo Institute of Clinical Medicine, Oslo, Norway (K.M.T., M.V.)
University of Oslo Institute of Clinical Medicine, Oslo, Norway; Cancer Registry of Norway and University of Oslo Institute of Basic Medical Sciences, Oslo, Norway, and University of Southern California Keck School of Medicine, Los Angeles, California (G.U.)
University of Oslo Institute of Clinical Medicine and Cancer Registry of Norway, Oslo, Norway, and Telemark Hospital, Skien, Norway (G.H.)
Disclaimer: Drs. Holme, Løberg, Kalager, and Bretthauer had full access to all data and take responsibility for the integrity of the data and accuracy of the analysis.
Grant Support: By research grants from the Norwegian government and the Norwegian Cancer Society. Work with the present manuscript was funded by research grants from the Norwegian Cancer Society, the Research Council of Norway, the South-East Regional Health Authority of Norway, the Fulbright Foundation, Sørlandet Hospital Kristiansand, and the National Institutes of Health.
Disclosures: Dr. Holme reports personal fees from Norgine outside the submitted work. Dr. Hernán reports grants from the National Institutes of Health during the conduct of the study. Dr. Hoff reports personal fees from Amgen Norway during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1441.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive 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: See the Supplement. Statistical code: Available from Dr. Løberg (e-mail, magnus.
Corresponding Author: Øyvind Holme, MD, PhD, Institute of Health and Society, Department of Health Management and Health Economics, University of Oslo, Postbox 1089 Blindern, 0318 Oslo, Norway; e-mail, oyvind.
Current Author Addresses: Drs. Holme, Løberg, Kalager, Bretthauer, and Aas: Institute of Health and Society, Department of Health Management and Health Economics, University of Oslo, Postbox 1089 Blindern, 0318 Oslo, Norway.
Drs. Ursin and Hoff: Cancer Registry of Norway, Postbox 5313 Majorstuen, 0304 Oslo, Norway.
Dr. Hernán: Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115.
Drs. Eide and Tveit: Oslo University Hospital. Postbox 4950 Nydalen, 0424 Oslo, Norway.
Dr. Skovlund: Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Dr. Lekven: University of Bergen Surgical Research Laboratory, Postbox 1400, 5021 Bergen, Norway.
Dr. Schneede: Umeå University Clinical Pharmacology Unit, SE-901 87 Umeå, Sweden.
Dr. Vatn: Institute of Clinical Medicine, University of Oslo, Postbox 1089 Blindern, 0318 Oslo, Norway.
Author Contributions: Conception and design: M. Løberg, M. Bretthauer, T.J. Eide, E. Skovlund, J. Schneede, K.M. Tveit, M. Vatn, G. Hoff.
Analysis and interpretation of the data: Ø. Holme, M. Løberg, M. Kalager, M. Bretthauer, M.A. Hernán, E. Aas, T.J. Eide, E. Skovlund, J. Schneede, G. Ursin.
Drafting of the article: Ø. Holme, M. Løberg, M. Kalager, M. Bretthauer, M.A. Hernán.
Critical revision of the article for important intellectual content: Ø. Holme, M. Løberg, M. Kalager, M. Bretthauer, M.A. Hernán, E. Aas, E. Skovlund, J. Schneede, K.M. Tveit, M. Vatn, G. Ursin, G. Hoff.
Final approval of the article: Ø. Holme, M. Løberg, M. Kalager, M. Bretthauer, M.A. Hernán, E. Aas, T.J. Eide, E. Skovlund, J. Lekven, J. Schneede, K.M. Tveit, M. Vatn, G. Ursin, G. Hoff.
Provision of study materials or patients: G. Hoff.
Statistical expertise: Ø. Holme, M. Løberg, M.A. Hernán.
Obtaining of funding: M. Løberg, M. Kalager, M. Bretthauer, M.A. Hernán, K.M. Tveit, G. Hoff.
Administrative, technical, or logistic support: J. Schneede, K.M. Tveit, G. Hoff.
Collection and assembly of data: M. Løberg, M. Bretthauer, T.J. Eide, J. Schneede, G. Hoff.
This article was published at Annals.org on 24 April 2018.
* Drs. Holme, Løberg, and Kalager contributed equally to this work.
† For members of the NORCCAP (Norwegian Colorectal Cancer Prevention) Study Group, see the Appendix.