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Colorectal Cancer Screening: An Updated Modeling Study for the US Preventive Services Task Force
Open accessAbstract
Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations. Objective: To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF. Design, Setting, and Participants: Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer. Exposures: Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed. Main Outcome and Measures: Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies. Results: Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer. Conclusions and Relevance: This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.
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“The sensitivity of colonoscopy for the detection of intestinal adenomas larger than 1 cm and CRC is estimated at 95%[22,68].”
From Risk factors, prevention and screening of colorectal cancer: A rising problem (2025) · cites this paper as [68]
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Multi-Cancer Early Detection Tests: State of the Art and Implications for Radiologists
Kang, S. K., Gulati, R., Moise, N., Hur, C., & Elkin, E. B. (2025) · Radiology · doi:10.1148/radiol.233448 · Cited by 4
Kwok, C., & Xu, X. (2025) · Health Promotion Journal of Australia · doi:10.1002/hpja.70059 · Cited by 4
A Scoping Review on Calibration Methods for Cancer Simulation Models
Zhang, Y., Lipa, N., & Alagöz, O. (2025) · Medical Decision Making · doi:10.1177/0272989x251353211 · Cited by 4
Meester, R. G. S., Piscitello, A. J., Duimstra, J. A., Liang, P. S., Shaukat, A., & Levin, T. R. (2025) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djaf277 · Cited by 4
“13 Outcomes Screening benefits included lifetime CRC cases averted, CRC deaths averted, and life-years gained (LYG); burdens included the total number of screening tests and colonoscopies (screening, follow-up, and surveillance); and the harms included the number of colonoscopy-related…”
InfluentialSelf-citationSapienza, M., Davis, C., & Boudes, M. (2025) · Oncology Reviews · doi:10.3389/or.2025.1653617 · Cited by 4
“Firstly, the validity and reliability of these models heavily depend on the quality and accuracy of the input data and assumptions used (62, 66).”
InfluentialPopulation-Level Health Benefits and Harms Associated With Buprenorphine/Naloxone vs Methadone
Enns, B., Guerra‐Alejos, B. C., Min, J. E., Carter, A., Siebert, U., & Nosyk, B. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.51337 · Cited by 4
Никонов, Е. Л., Kuvaev, R. O., Zharova, M. E., Kuvaeva, A. A., & Kashin, S. V. (2024) · Russian Journal of Evidence-Based Gastroenterology · doi:10.17116/dokgastro20241304169 · Cited by 4
Modeled Cost-Effectiveness of a Rideshare Program to Facilitate Colonoscopy Completion
Issaka, R. B., Matrajt, L., de Lima, P. N., & Rutter, C. M. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.30515 · Cited by 4
Self-citationEffects of Screening Colonoscopy: Evidence From Observational and Interventional Studies
Brenner, H., Sergeev, D., Heisser, T., & Hoffmeister, M. (2025) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000003814 · Cited by 4
Change in onset age of first primary colorectal cancer in the USA
Liu, A., Zheng, Y., Yang, P., Chu, H., & Hou, X. (2023) · International Journal of Colorectal Disease · doi:10.1007/s00384-023-04336-6 · Cited by 4
“Recent age-period-cohort analysis shows that the risk of CRC has increased in people younger than 50 years in the past decades [22] and lowering the age of starting screening from 50 to 45 will increase life-years gained [23].”
Wei, J., Zhao, S., & Bai, Y. (2024) · Gastroenterology · doi:10.1053/j.gastro.2024.01.014 · Cited by 4
Non-gastrointestinal symptom burden following colorectal cancer treatment—a systematic review
Fernandes, D., Nelson, D., Ortega, M., Siriwardena, A. N., Law, G. R., & Andreyev, J. N. (2024) · Supportive Care in Cancer · doi:10.1007/s00520-024-08903-7 · Cited by 4
“This can include eating a diet high in processed meats [3], low in fruit and vegetables [4] and high alcohol consumption [5].”
Does Colonoscopy as a First Screening Test Still Make Sense?—Counterpoint
Chuang, M. P.-C., & Chiu, H. (2024) · Digestive Diseases and Sciences · doi:10.1007/s10620-024-08695-0 · Cited by 5
Sergeev, D., Heisser, T., Hoffmeister, M., & Brenner, H. (2025) · International Journal of Cancer · doi:10.1002/ijc.35322 · Cited by 4
Donderici, E. Y., Forbes, S. P., Zhang, N. J., Schafer, G., Raymond, V. M., Das, A. K., Eagle, C. J., Talasaz, A. H., & Grady, W. M. (2025) · Expert Review of Pharmacoeconomics & Outcomes Research · doi:10.1080/14737167.2025.2458044 · Cited by 5
Lew, J., Luo, Q., Worthington, J., Ge, H., He, E., Steinberg, J., Caruana, M., O’Connell, D. L., Feletto, E., & Canfell, K. (2025) · Medical Decision Making · doi:10.1177/0272989x251314050 · Cited by 4
“42,52 Unlike that study, our analysis uses novel methods to incorporate both increasing CRC incidence for people younger than 50 y and slightly lower CRC incidence rates for people older than 50 y (potentially due to opportunistic, non-NBCSP screening among other risk factor trends) in our…”
The NCC mathematical modeling framework for decision-making of six major cancers
Xia, C., & Chen, W. (2022) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2022.11.002 · Cited by 4
Lin, G. J., Hein, D., Liu, P., Singal, A. G., & Sanford, N. N. (2024) · Cancers · doi:10.3390/cancers16061110 · Cited by 3
“Focusing further on younger patients, the lowering of screening age was based upon modeling study projections and the rising incidence of colorectal cancer in individuals aged less than 50 years [19].”
Greene, M., Gohil, S., Stieber, B., Ozbay, A. B., Le, Q. A., Kakuturu, R., LeMaster, J. W., Dore, M. M., Fendrick, A. M., Anderson, J. C., et al. (2025) · Current Medical Research and Opinion · doi:10.1080/03007995.2025.2565442 · Cited by 3
Barnell, E. K., Levin, T. R., Gupta, S. N., Carethers, J. M., Shaukat, A., Kruse, K. R., Ghannam, R. B., & Lieberman, D. A. (2026) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000002336 · Cited by 3
Rudolph, J. E., Calkins, K. L., Zhang, X., Zhou, Y., Pirsl, F., Xu, X., Wentz, E., Lau, B. M., & Joshu, C. E. (2024) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofae246 · Cited by 3
Meester, R. G. S., & Ladabaum, U. (2024) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkae077 · Cited by 4
“For burden–benefit analysis, we evaluated required colonoscopies/life-year gained, similar to the USPSTF (12).”
BackgroundMethodInfluentialSelf-citationNguyen, C. M., Yeh, P. G., Nguyen, M. P., Johnson, T. S., Koo, H., Champion, V. L., Skaar, T. C., Lairson, D. R., Monahan, P. O., Imperiale, T. F., et al. (2025) · Cancer Research Communications · doi:10.1158/2767-9764.crc-25-0367 · Cited by 3
“Although colorectal cancer incidence has declined since the mid-1990s because of widespread screening (13–15), recent trends indicate a concerning increase in advanced-stage diagnoses, particularly among individuals under 65 years of age (2, 16–20).”
Use of 2-Stage Modeling to Identify How Colorectal Cancer Risk Changes With Period and Cohort
DeYoreo, M., Rutter, C. M., & Lee, S. D. (2022) · American Journal of Epidemiology · doi:10.1093/aje/kwac177 · Cited by 3
Self-citationEarly-Onset Colorectal Cancer—A Retrospective Study from a Tertiary Referral Hospital in Romania
Savu, E., Şurlin, V., Vasile, L., Petrescu, I. O., Singer, C. E., Pirici, D. N., & Mogoantă, S. Ş. (2024) · Diagnostics · doi:10.3390/diagnostics14101052 · Cited by 3
“Nevertheless, this shift in attitude would translate into a moderate elevation in life years gained and a reduction in both colorectal cancer incidence and mortalities when contrasted with the initiation of screening at 50 years of age [13,59].”
BackgroundHarlass, M., Knudsen, A. B., Nieboer, D., van Duuren, L. A., Kuntz, K. M., Rutter, C. M., de Lima, P. N., Collier, N. T., Ozik, J., Hahn, A. I., et al. (2025) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djaf149 · Cited by 3
Self-citationDevelopment and validation of a histology-specific natural history model of ovarian cancer
Ishizawa, S., Eghbali‐Zarch, M., Nargund, R. S., Sarayi, S. M. M. J., Niu, J., Hemmati, M., Tumbarello, M., Schaefer, A. J., Lu, K. H., Giordano, S. H., et al. (2025) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2025.06.063 · Cited by 3
How Would You Screen This Patient for Colorectal Cancer?
Burns, R. B., Mangione, C. M., Weinberg, D. S., & Kanjee, Z. (2022) · Annals of Internal Medicine · doi:10.7326/m22-1961 · Cited by 3
Colonoscopies save lives. Why did a trial suggest they might not?
Sohn, E. (2023) · Nature · doi:10.1038/d41586-023-00020-5 · Cited by 3
A History of Health Economics and Healthcare Delivery Research at the National Cancer Institute
Doria-Rose, V. P., Breen, N., Brown, M. L., Feuer, E. J., Geiger, A. M., Kessler, L. G., Lipscomb, J., Warren, J. L., & Yabroff, K. R. (2022) · JNCI Monographs · doi:10.1093/jncimonographs/lgac003 · Cited by 3
Self-citationSchoenborn, N. L., Pollack, C. E., Gupta, S. N., & Boyd, C. M. (2023) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002193 · Cited by 3
“One approach may be to leverage the robust simulation models that are used to inform CRC screening recommendations (25).”
BackgroundRobustness Analysis of Colorectal Cancer Colonoscopy Screening StrategiesPreprint
de Lima, P. N., Rutter, C. M., Maerzluft, C., Ozik, J., & Collier, N. T. (2023) · medRxiv · doi:10.1101/2023.03.07.23286939 · Cited by 3
“Following comparable studies (Knudsen et al. 2021a), perfect adherence to screening is assumed across all model runs.”
BackgroundMethodResultInfluentialSelf-citationZhang, M., Zhang, Y., Zhang, W., Zhang, Y., Zhao, L., Jing, H., Gao, X., Nie, Z., Zhu, S., Zhang, S., et al. (2024) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16468 · Cited by 2
Metadata
- Authors
- Knudsen, A. B., Rutter, C. M., Peterse, E. F. P., Lietz, A. P., Seguin, C. L., Meester, R. G. S., Perdue, L. A., Lin, J. S., Siegel, R. L., Doria-Rose, V. P., Feuer, E. J., Zauber, A. G., Kuntz, K. M., & Lansdorp-Vogelaar, I.
- Affiliations
- Harvard University (US)
- RAND Corporation (US)
- Erasmus MC (NL)
- Massachusetts General Hospital (US)
- Kaiser Permanente (US)
- American Cancer Society (US)
- National Cancer Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Minnesota (US)
- Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands
- Corresponding author
- Knudsen, Amy B.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2021-05-18
- Volume
- 325
- Issue
- 19
- Pages
- 1998
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC8409520
- OpenAlex
- W3162019711
- Cited by
- 327
- References
- 40
- Citations by year
- 2026: 44 · 2025: 70 · 2024: 76 · 2023: 63 · 2022: 55 · 2021: 16
- FWCI
- 19.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services
- Kaiser Permanente
- Agency for Healthcare Research and Quality
- National Cancer Institute (U01CA199335, U01CA253913, P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer screening, screening guidelines, life-years gained, fecal immunochemical test, flexible sigmoidoscopy, computed tomography colonography, screening frequency, screening age, efficiency ratio, USPSTF recommendations, average-risk population, microsimulation model, cost-effectiveness, colorectal cancer incidence
- MeSH terms
- Adult, Aged, Aged, 80 and over, Colonoscopy, Female, Humans, Life Expectancy, Male, Middle Aged, Occult Blood, Risk, Sensitivity and Specificity, Sex Factors, Sigmoidoscopy, Tomography, X-Ray Computed, Colorectal Neoplasms, Models, Statistical, Cohort Studies, Early Detection of Cancer
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