Cost-Effectiveness of Risk-Stratified Colorectal Cancer Screening Based on Polygenic Risk: Current Status and Future Potential

Author:

Naber Steffie K1ORCID,Kundu Suman2,Kuntz Karen M3,Dotson W David4ORCID,Williams Marc S5ORCID,Zauber Ann G6,Calonge Ned7,Zallen Doris T89,Ganiats Theodore G10,Webber Elizabeth M11,Goddard Katrina A B11,Henrikson Nora B12,van Ballegooijen Marjolein1,Janssens A Cecile J W1314,Lansdorp-Vogelaar Iris1

Affiliation:

1. Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands

2. Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN

3. Division of Health Policy & Management, University of Minnesota School of Public Health, Minneapolis, MN

4. Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA

5. Genomic Medicine Institute, Geisinger, Danville, PA

6. Memorial Sloan Kettering Cancer Center, New York, NY

7. The Colorado Trust, Denver, CO

8. Department of Science, Technology, and Society, Virginia Tech, Blacksburg, VA

9. Department of Basic Science Education, Virginia Tech-Carilion School of Medicine, Roanoke, VA

10. Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA

11. Center for Health Research, Kaiser Permanente, Portland, OR

12. Kaiser Permanente Washington Health Research Institute, Seattle, WA

13. Department of Clinical Genetics, EMGO Institute for Health and Care Research, Section Community Genetics, VU University Medical Center, Amsterdam, the Netherlands

14. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA

Abstract

Abstract Background Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be. Methods The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65–0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40–60 years), end age (70–85 years), and interval (1–20 years). Results With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40–80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation. Conclusions Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.

Funder

National Cancer Institute

Cancer Intervention and Surveillance Modeling Network

Evaluation of Genomic Applications in Practice and Prevention

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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