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Original Research |

Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening: A Retrospective Cohort StudyFecal Immunochemical Test Performance Characteristics

Christopher D. Jensen, PhD, MPH; Douglas A. Corley, MD, PhD; Virginia P. Quinn, PhD, MPH; Chyke A. Doubeni, MD, MPH; Ann G. Zauber, PhD; Jeffrey K. Lee, MD, MAS; Wei K. Zhao, MPH; Amy R. Marks, MPH; Joanne E. Schottinger, MD; Nirupa R. Ghai, PhD; Alexander T. Lee, MD; Richard Contreras, MS; Carrie N. Klabunde, PhD; Charles P. Quesenberry, PhD; Theodore R. Levin, MD; and Pauline A. Mysliwiec, MD
[+] Article, Author, and Disclosure Information

This article was published at www.annals.org on 26 January 2016.


From Kaiser Permanente Northern California, Oakland, California; Kaiser Permanente Southern California, Pasadena, California; University of Pennsylvania, Philadelphia, Pennsylvania; Memorial Sloan Kettering Cancer Center, New York, New York; University of California, San Francisco, San Francisco, California; and National Institutes of Health, Bethesda, Maryland.

Grant Support: The study was conducted through the National Cancer Institute–funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium (U54 CA163262 [Dr. Corley]).

Disclosures: Drs. Jensen, Corley, Quesenberry, and Levin report grant support from the National Cancer Institute during the conduct of the study. Dr. Quinn reports grant support from the National Institutes of Health during the conduct of the study. Dr. Doubeni reports compensation for 1-time consultancy (Exact Sciences) outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0983.

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.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Corley (e-mail, douglas.corley@kp.org).

Corresponding Author: Douglas A. Corley, MD, PhD, Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612; e-mail, douglas.corley@kp.org.

Current Author Addresses: Drs. Jensen, Corley, and Quesenberry; Ms. Zhao; and Ms. Marks: Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612.

Drs. Ghai and Quinn and Mr. Contreras: Department of Research & Evaluation, Kaiser Permanente Southern California, 100 South Los Robles, 2nd Floor, Pasadena, CA 91101.

Dr. Doubeni: Department of Family Medicine and Community Health, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Gate 2, Philadelphia, PA 19104.

Dr. Zauber: Memorial Sloan Kettering Cancer Center, 485 Lexington Avenue, 2063A, New York, NY 10017.

Dr. Lee: Division of Gastroenterology, University of California, San Francisco, 1701 Divisadero Street, Suite 120, San Francisco, CA 94115.

Dr. Schottinger: Kaiser Permanente Southern California Permanente Medical Group, 393 East Walnut Street, Pasadena, CA 91188.

Dr. Lee: Kaiser Permanente Southern California Permanente Medical Group, Woodland Hills Medical Center, 5601 De Soto Avenue, Woodland Hills, CA 91365.

Dr. Klabunde: Office of Disease Prevention, National Institutes of Health, 6100 Executive Boulevard, Suite 2B03, Rockville, MD 20852.

Dr. Levin: Kaiser Permanente Medical Center, 1425 South Main Street, Walnut Creek, CA 94596.

Dr. Mysliwiec: The Permanente Medical Group, 975 Sereno Drive, Vallejo, CA 94589.

Author Contributions: Conception and design: C.D. Jensen, D.A. Corley, V.P. Quinn, C.A. Doubeni, J.K. Lee, A.R. Marks, A.T. Lee, C.N. Klabunde, T.R. Levin, P.A. Mysliwiec.

Analysis and interpretation of the data: C.D. Jensen, D.A. Corley, V.P. Quinn, C.A. Doubeni, A.G. Zauber, J.K. Lee, W.K. Zhao, C.N. Klabunde, C.P. Quesenberry, T.R. Levin, P.A. Mysliwiec.

Drafting of the article: C.D. Jensen, D.A. Corley, V.P. Quinn, A.R. Marks, J.E. Schottinger, N.R. Ghai, P.A. Mysliwiec.

Critical revision of the article for important intellectual content: C.D. Jensen, D.A. Corley, V.P. Quinn, C.A. Doubeni, A.G. Zauber, J.K. Lee, N.R. Ghai, A.T. Lee, C.N. Klabunde, T.R. Levin, P.A. Mysliwiec.

Final approval of the article: C.D. Jensen, D.A. Corley, V.P. Quinn, C.A. Doubeni, A.G. Zauber, J.K. Lee, J.E. Schottinger, N.R. Ghai, A.T. Lee, C.N. Klabunde, C.P. Quesenberry, T.R. Levin, P.A. Mysliwiec.

Provision of study materials or patients: D.A. Corley, V.P. Quinn, A.T. Lee.

Statistical expertise: D.A. Corley, A.G. Zauber, A.R. Marks, C.P. Quesenberry.

Obtaining of funding: D.A. Corley, V.P. Quinn, C.A. Doubeni, C.P. Quesenberry, T.R. Levin,

Administrative, technical, or logistic support: D.A. Corley, V.P. Quinn, C.A. Doubeni, J.K. Lee, A.R. Marks, P.A. Mysliwiec.

Collection and assembly of data: C.D. Jensen, D.A. Corley, V.P. Quinn, C.A. Doubeni, R. Contreras, T.R. Levin, P.A. Mysliwiec.


Ann Intern Med. 2016;164(7):456-463. doi:10.7326/M15-0983
© 2016 American College of Physicians
Text Size: A A A

Background: The fecal immunochemical test (FIT) is a common method for colorectal cancer (CRC) screening, yet its acceptability and performance over several rounds of annual testing are largely unknown.

Objective: To assess FIT performance characteristics over 4 rounds of annual screening.

Design: Retrospective cohort study.

Setting: Kaiser Permanente Northern and Southern California.

Patients: 323 349 health plan members aged 50 to 70 years on their FIT mailing date in 2007 or 2008 who completed the first round of FIT and were followed for up to 4 screening rounds.

Measurements: Screening participation, FIT positivity (≥20 µg of hemoglobin/g), positive predictive values for adenoma and CRC, and FIT sensitivity for detecting CRC obtained from Kaiser Permanente electronic databases and cancer registries.

Results: Of the patients invited for screening, 48.2% participated in round 1. Of those who remained eligible, 75.3% to 86.1% participated in subsequent rounds. Median follow-up was 4.0 years, and 32% of round 1 participants crossed over to endoscopy over 4 screening rounds—7.0% due to a positive FIT result. The FIT positivity rate (5.0%) and positive predictive values (adenoma, 51.5%; CRC, 3.4%) were highest in round 1. Overall, programmatic FIT screening detected 80.4% of patients with CRC diagnosed within 1 year of testing, including 84.5% in round 1 and 73.4% to 78.0% in subsequent rounds.

Limitation: Screening detection, rather than long-term cancer prevention, was evaluated.

Conclusion: Annual FIT screening was associated with high sensitivity for CRC, with high adherence to annual follow-up screening among initial participants. The findings indicate that annual programmatic FIT screening is feasible and effective for population-level CRC screening.

Primary Funding Source: National Institutes of Health.

Figures

Grahic Jump Location
Figure.

Study flow diagram.*

The figure includes 1192 patients with CRC who were screened by FIT the year before diagnosis. Further, there were 118 additional patients with CRC diagnosed more than 1 y beyond the FIT screening date and 101 additional patients diagnosed with CRC who either crossed over to endoscopy in subsequent rounds or terminated health plan membership but then rejoined. CRC = colorectal cancer; FIT = fecal immunochemical test.

* Shading indicates where patients were censored or became ineligible for subsequent FIT screening.

† Patients were eligible for the initial FIT mailing if they were aged 50 to 70 y and had ≥1 y of membership. See Methods section for exclusions.

‡ Number censored because of CRC and includes patients with CRC diagnosed within 1 y after their FIT result.

Grahic Jump Location
Grahic Jump Location
Appendix Figure.

Pattern of FIT performance measures over 4 rounds of annual screening.*

CRC = colorectal cancer; FIT = fecal immunochemical testing; PPV = positive predictive value.

* See Tables 2 and 3 for numerators, denominators, and percentages.

† Data available for Kaiser Permanente Northern California only.

‡ Advanced adenoma defined as adenomas with villous or tubulovillous histology.

Grahic Jump Location

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Comment
Posted on February 9, 2016
Alain Braillon, MD
University Hospital, France
Conflict of Interest: None Declared
Jensen et al must be commended for studying the Fecal Immunochemical Test (FIT) over 4 annual rounds for colorectal cancer screening as results about FIT were only available for the first round screening yet.(1,2) However, their report raises several questions.
First, performance cannot be limited to sensibility round by round. The report should have presented sensibility not as per protocol but as intention to screen: adenoma and cancer found divided by the number mailed. Moreover there is no mention about either false negative or false positive, the latter being the drawback of increasing the sensitivity by lowering the cut off level.
Second the advantages of FIT remains theoric in the real life setting. Four rounds remains a short period of time as the first randomized controlled trials for bowel cancer screening showed that mortality was reduced at best after 8 to 13 years of screening in two trials and not until after 15 to18 years of screening in another two trials. The report should have presented the percentage of those mailed and who completed the four rounds or had a colonoscopy. Last, only 78.4% of participants with positive FIT results had follow-up colonoscopy.(1)
Third, the bowel cancer screening issue cannot be limited to faecal tests, either guaiac or FIT. Endoscopy or CT-colonography are the primary screening methods used in the United States (7 million screening colonoscopies performed in the United States in 2004) and in several European countries (eg. Germany, Poland) or the method chose by gastroenterologists for themselves. An ongoing well designed and robust randomized control trial has just reported preliminary results comparing FIT (first round of three biennial rounds) vs endoscopy and CT-colonography (single round).(3) Dectection rates for advanced neoplasia are the lowest for first-round FIT (1.7% for first-round) 5.5% for CT-colonography and 7.2% for endoscopy.
There is no robust evidence yet that FIT improves screening performance in the real life setting. However, there is a simple way to improve effectiveness and also fairness without extra cost. It is to stratify screening on sex as age-specific prevalence for advanced colorectal neoplasms is more than twice higher in men than in women!(4) A finding confirmed by Jensen et al study.(1)

1 Jensen CD, Corley DA, Quinn VP, Doubeni CA, Zauber AG, Lee JK, et al. Fecal Immunochemical Test program performance over 4 Rounds of annual screening: A retrospective cohort study. Ann Intern Med 2016 Jan 26. doi: 10.7326/M15-0983.
2 Braillon A. Can surrogate end points from a first-round screening be reliable for colorectal cancer screening? Gastroenterology 2012;142:e29.
3 Sali LMM, Falchini M, Ventura L, et al. Reduced and full-preparation CT colonography, fecal immunochemical test and colonoscopy for population screening of colorectal cancer: a randomized trial. J Natl Cancer Inst 2016. Online. doi: 10.1093/jnci/djv319
4 Brenner H, Altenhofen L, Hoffmeister M. Sex, age, and birth cohort effects in colorectal neoplasms: a cohort analysis. Ann Intern Med 2010;152:697-703.
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