Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force

Abstract

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations.

Objective: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.

Design, setting, and participants: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.

Exposures: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed.

Main outcomes and measures: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds.

Results: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG).

Conclusions and relevance: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.

Figure 1. Natural History of Colorectal Cancer and the Effects of Screening as Simulated by SimCRC, MISCAN, and CRC-SPIN

The opportunity to intervene in the natural history through screening is noted in red. Screening can either remove an adenoma, thus moving a person to the “no lesion” state, or diagnose a preclinical cancer, which, if detected at an earlier stage, may be more amenable to treatment. ^aThe SimCRC and MISCAN models simulate discrete adenoma size categories (ie, 1–5 mm, 6–9 mm, ≥10 mm). The CRC-SPIN model simulates continuous adenoma size. ^bScreening may allow for detection of cancer at an earlier stage than symptom-detected cancer and therefore create the conditions necessary for a better prognosis.

Figure 2. Predictions From the Natural History Models of Colorectal Cancer for Adenoma Prevalence and Colorectal Cancer Incidence by Age

The calibrated models were used to project estimates for ages for which calibration data were not available. A, Adenoma prevalence from autopsy studies^– and as predicted by the models. Multiple observations at each data point reflect estimates from different studies. The SimCRC and MISCAN models were each simultaneously calibrated to adenoma prevalence estimates from 10 autopsy studies.^– The CRC-SPIN model incorporates the distribution of adenoma risk based on a Bayesianmeta-analysis of the 10 autopsy studies.^– B, Colorectal cancer cases per 100 000 from the Surveillance, Epidemiology, and End Results (SEER) program (1975–1979) and as predicted by the models. The models were calibrated to SEER colorectal cancer incidence rates in 1975–1979 because this period represents colorectal cancer incidence in the United States when there was little or no screening for the disease. (SEER data do not distinguish between screen-detected cancer and clinically detected cancer.)

Figure 3. Lifetime Number of Colonoscopies and Life-Years Gained for a Cohort of 40-Year-Olds for Colonoscopy Screening Strategies

Labeled strategies are efficient or near-efficient with an age to begin screening of 50 or 55 years. ^aStrategy is near-efficient (it is weakly dominated and its life-years gained [LYG] are within 98%of the efficient frontier).

Figure 4. Lifetime Number of Colonoscopies and Life-Years Gained for a Cohort of 40-Year-Olds for Stool-Based Screening Strategies

Labeled strategies are efficient or near-efficient with an age to begin screening of 50 or 55 years. ^aStrategy is near-efficient (it is weakly dominated and its life-years gained [LYG] are within 98%of the efficient frontier).