Kevin Selby, MD, MAS; Christopher D. Jensen, PhD; Jeffrey K. Lee, MD, MAS; Chyke A. Doubeni, MD, MPH; Joanne E. Schottinger, MD; Wei K. Zhao, MPH; Jessica Chubak, PhD; Ethan Halm, MD, MPH; Nirupa R. Ghai, PhD; Richard Contreras, MS; Celette Skinner, PhD; Aruna Kamineni, PhD; Theodore R. Levin, MD; Douglas A. Corley, MD, PhD
Note: Dr. Selby had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Acknowledgment: The authors thank Peter Bacchetti and Robert Hiatt for their detailed feedback during manuscript preparation.
Grant Support: This study was conducted within the NCI-funded (grant U54 CA163262) PROSPR II consortium, which conducts multisite, coordinated, transdisciplinary research to evaluate and improve cancer screening processes. It was also funded by grants K07 CA212057 from the NCI and BIL KFS-3720-08-2015 from the Swiss Cancer Research Foundation.
Disclosures: Dr. Selby reports grants from the Swiss Cancer Research Foundation during the conduct of the study. Drs. Jensen and Levin report grants from NCI during the conduct of the study. Dr. Doubeni is a member of the U.S. Preventive Services Task Force and a topic author for UpToDate. Dr. Corley reports grants from the National Institutes of Health 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=M18-0244.
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 Proctor & Gamble, Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Not available. Statistical code: Available from Dr. Selby (e-mail, email@example.com). Data set: May be available for collaborative efforts by contacting Dr. Corley (e-mail, firstname.lastname@example.org).
Corresponding Author: Kevin Selby, MD, MAS, Department of Ambulatory Care and Community Medicine, University of Lausanne, Rue de Bugnon 44, 1011 Lausanne, Switzerland; e-mail: email@example.com.
Current Author Addresses: Dr. Selby: Department of Ambulatory Care and Community Medicine, University of Lausanne, Rue de Bugnon 44, 1011 Lausanne, Switzerland.
Drs. Jensen, Lee, and Corley, and Ms. Zhao: Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612.
Dr. Doubeni: Department of Family Medicine and Community Health, Perelman School of Medicine, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104.
Dr. Schottinger: Kaiser Permanente Southern California Permanente Medical Group, 393 East Walnut Street, Pasadena, CA 91188.
Drs. Chubak and Kamineni: Kaiser Permanente Washington Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101.
Drs. Halm and Skinner: University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390.
Dr. Ghai: SCAL Quality and Risk Management, 393 East Walnut Street, 5th Floor, Pasadena, CA 91188.
Mr. Contreras: Department of Research and Evaluation, Kaiser Permanente Southern California, 100 South Los Robles Avenue, 2nd Floor, Pasadena, CA 91101.
Dr. Levin: Kaiser Permanente Medical Center, 1425 South Main Street, Walnut Creek, CA 94596.
Author Contributions: Conception and design: K. Selby, C.D. Jensen, J.K. Lee, C.A. Doubeni, D.A. Corley.
Analysis and interpretation of the data: K. Selby, C.D. Jensen, J.K. Lee, C.A. Doubeni, J.E. Schottinger, E. Halm, C. Skinner, D.A. Corley.
Drafting of the article: K. Selby, C.D. Jensen, J.K. Lee, C.A. Doubeni, J.E. Schottinger, N.R. Ghai, T.R. Levin, D.A. Corley.
Critical revision for important intellectual content: K. Selby, C.D. Jensen, J.K. Lee, C.A. Doubeni, J. Chubak, E. Halm, C. Skinner, A. Kamineni, T.R. Levin, D.A. Corley.
Final approval of the article: K. Selby, C.D. Jensen, J.K. Lee, C.A. Doubeni, J.E. Schottinger, W.K. Zhao, J. Chubak, E. Halm, N.R. Ghai, R. Contreras, C. Skinner, A. Kamineni, T.R. Levin, D.A. Corley.
Statistical expertise: D.A. Corley.
Obtaining of funding: K. Selby, C.D. Jensen, C.A. Doubeni, A. Kamineni, T.R. Levin, D.A. Corley.
Administrative, technical, or logistic support: C.A. Doubeni, N.R. Ghai.
Collection and assembly of data: K. Selby, C.A. Doubeni, J.E. Schottinger, W.K. Zhao, N.R. Ghai, R. Contreras, T.R. Levin, D.A. Corley.
The fecal immunochemical test (FIT) is commonly used for colorectal cancer (CRC) screening. Despite demographic variations in stool hemoglobin concentrations, few data exist regarding optimal positivity thresholds by age and sex.
To identify programmatic (multitest) FIT performance characteristics and optimal FIT quantitative hemoglobin positivity thresholds in a large, population-based, screening program.
Retrospective cohort study.
Kaiser Permanente Northern and Southern California.
Adults aged 50 to 75 years who were eligible for screening and had baseline quantitative FIT results (2013 to 2014) and 2 years of follow-up. Nearly two thirds (411 241) had FIT screening in the previous 2 years.
FIT programmatic sensitivity for CRC and number of positive test results per cancer case detected, overall and by age and sex.
Of 640 859 persons who completed a baseline FIT and were followed for 2 years, 481 817 (75%) had at least 1 additional FIT and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%) at 30 µg/g to 925 (74.3%) at 20 µg/g and 987 (79.3%) at 10 µg/g; the number of positive test results per cancer case detected increased from 43 at 30 µg/g to 52 at 20 µg/g and 85 at 10 µg/g. Reducing the positivity threshold from 20 to 15 µg/g would detect 3% more cancer cases and require 23% more colonoscopies. At the conventional FIT threshold of 20 µg/g, programmatic sensitivity decreased with increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75 years, respectively; P = 0.009) and was higher in men than women (77.0% vs. 70.6%; P = 0.011).
Information on advanced adenoma was lacking.
Increased cancer detection at lower positivity thresholds is counterbalanced by substantial increases in positive tests. Tailored thresholds may provide screening benefits that are more equal among different demographic groups, depending on local resources.
National Cancer Institute.
Selby K, Jensen CD, Lee JK, Doubeni CA, Schottinger JE, Zhao WK, et al. Influence of Varying Quantitative Fecal Immunochemical Test Positivity Thresholds on Colorectal Cancer Detection: A Community-Based Cohort Study. Ann Intern Med. [Epub ahead of print 18 September 2018]169:439–447. doi: 10.7326/M18-0244
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Published: Ann Intern Med. 2018;169(7):439-447.
Published at www.annals.org on 18 September 2018
Cancer Screening/Prevention, Colorectal Cancer, Gastroenterology/Hepatology, Gastrointestinal Cancer, Hematology/Oncology.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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