Colorectal Cancer Screening: An Updated Modeling Study for the US Preventive Services Task Force

Abstract

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.

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

The opportunity to intervene in the natural history through screening (adenoma detection and removal, and early detection) is noted by the dotted lines. Screening can either remove a precancerous lesion (ie, 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. Each person’s life history is simulated in the absence of screening and in the presence of screening, such that the effect of a given screening strategy on each simulated person’s outcomes are known. ^a Simulation Model of CRC (SimCRC) and Microsimulation Screening Analysis (MISCAN) simulate categorical adenoma size (1 to <6 mm; 6 to <10 mm, ≥10 mm), whereas CRC Simulated Population Model for Incidence and Natural History (CRC-SPIN) simulates continuous adenoma size. SimCRC and CRC-SPIN assume that all adenomas have the potential to progress to colorectal cancer, whereas MISCAN assumes that some adenomas are nonprogressive (ie, they do not grow or progress to cancer after reaching a certain size category) and that the likelihood that an adenoma is progressive increases with age. None of the models simulate adenoma histology.

Figure 2.. Lifetime Number of Colonoscopies and Life-Years Gained for a Cohort of 40-year-olds for Colonoscopy Screening Strategies^a

CRC-SPIN indicates CRC Simulated Population Model for Incidence and Natural History; MISCAN, Microsimulation Screening Analysis; SimCRC, Simulation Model of CRC. ^a Analyses assume an increased population incidence of colorectal cancer based on an incidence rate ratio comparing incidence among current 20- to 44-year-olds (ie, in 2012–2016) vs 20- to 44-year-olds in the time period used for initial model calibration (ie, 1975–1979) of 1.19. An interactive version of this figure is available at https://resources.cisnet.cancer.gov/projects/#crcr/uspstf2021

Figure 3.. Lifetime Number of Colonoscopies and Life-Years Gained for a Cohort of 40-year-olds for Stool-Based Screening Strategies^a

See Figure 2 legend for expanded abbreviations. ^a Analyses assume an increased population incidence of colorectal cancer based on an incidence rate ratio comparing incidence among current 20- to 44-year-olds (ie, in 2012–2016) vs 20- to 44-year-olds in the time period used for initial model calibration (ie, 1975–1979) of 1.19. An interactive version of this figure is available at https://resources.cisnet.cancer.gov/projects/#crcr/uspstf2021

Figure 4.. Benefits of Colorectal Cancer Screening Strategies Highlighted by the US Preventive Services Task Force in 2016 and the Change in Outcomes When Screening is Started at Age 45 Years Instead of Age 50

COL indicates colonoscopy; CRC colorectal cancer; CRC-SPIN, CRC Simulated Population Model for Incidence and Natural History; CTC, computed tomography colonography; FIT indicates fecal immunochemical test (with positivity cutoff for of 20 μg of hemoglobin per gram of feces); sDNA-FIT, multitarget stool DNA test with a fecal immunochemical assay; SIG, flexible sigmoidoscopy; SimCRC, Simulation Model of CRC. ^a Outcomes are expressed over the lifetimes of 1000 40-year-olds who start screening at age 45 or at age 50 and are screened to age 75, assuming an increased population incidence of colorectal cancer based on an incidence rate ratio comparing incidence among current 20- to 44-year-olds (ie, in 2012–2016) vs 20- to 44-year-olds in the time period used for initial model calibration (ie, 1975–1979) of 1.19. ^b Compared with other options for stool-based screening, this strategy was not estimated to provide an efficient balance of the burden (ie, lifetime number of colonoscopies) and the benefit (life-years gained) of screening.

Figure 5.. Complications, Colonoscopy Burden, and Non-Colonoscopy Burden of Colorectal Cancer Screening Strategies Highlighted by the USPSTF in 2016 and the Change in Outcomes When Screening is Started at Age 45 Years Instead of Age 50

See Figure 4 legend for expanded abbreviations. ^a Outcomes are expressed over the lifetimes of 1000 40-year-olds who start screening at age 45 or at age 50 and are screened to age 75, assuming an increased population incidence of colorectal cancer based on an incidence rate ratio comparing incidence among current 20- to 44-year-olds (ie, in 2012–2016) vs 20- to 44-year-olds in the time period used for initial model calibration (ie, 1975–1979) of 1.19. ^b Compared with other options for stool-based screening, this strategy was not estimated to provide an efficient balance of the burden (ie, lifetime number of colonoscopies) and the benefit (life-years gained) of screening. ^c Other (noncolonoscopy) tests include FIT, sDNA-FIT, CTC, SIG.