Abstract

INTRODUCTION: Colonoscopy (COL) non-adherence following a positive non-invasive colorectal cancer (CRC) screening test (e.g., multitarget stool DNA [mt-sDNA], fecal immunochemical test [FIT]) undermines the achievable benefits of screening. Given wide variations in the limited data reporting COL adherence after a positive non-invasive test, microsimulation modeling was used to estimate the clinical implications of this understudied input. METHODS: An average-risk US population cohort free of diagnosed CRC at age 40 that underwent triennial mt-sDNA or annual FIT screening from ages 50 to 75 was simulated using the validated CRC-AIM model. Three scenarios were modeled: (S1) assumed 100% adherence for initial screening and COL follow-up; (S2) reported adherence rates for initial mt-sDNA (71%) or FIT (43%) screening, with assumed 100% adherence to COL follow-up; and (S3) reported adherence rates for initial mt-sDNA or FIT screening and reported adherence rates for COL follow-up after positive mt-sDNA (73%) or FIT (47%). Sensitivity analyses were performed using 100% and reported adherence rates for mt-sDNA and FIT screening, with COL follow-up adherence ranging from 40%-100%. Patients without a COL follow-up were assumed to be non-adherent until CRC symptom onset. Outcomes for each scenario are per 1000 individuals. RESULTS: S1, S2, and S3 each yielded life-years gained (LYG) and reductions in CRC incidence and CRC mortality with either mt-sDNA or FIT screening vs no CRC screening (Table 1). Estimated LYG for mt-sDNA and FIT were 297 and 316 for S1, 284 and 245 for S2, and 203 and 113 for S3, respectively. Reductions in CRC incidence for mt-sDNA and FIT were 64% and 68% for S1, 61% and 50% for S2, and 43% and 23% for S3, respectively; reductions in CRC mortality were 72% and 76% for S1, 69% and 59% for S2, and 49% and 27% for S3, respectively. With assumed 100% adherence to mt-sDNA or FIT screening, the LYG transition was at 45% (LYG = 128) and 40% (LYG = 119) adherence for COL follow-up, respectively (Figure 1). At reported adherence for stool-tests, the additional LYG for mt-sDNA vs FIT ranged from 12 to 188 as follow-up COL adherence increased from 40% to 100% (Figure 2). CONCLUSION: These modeling analyses demonstrate that the inclusion of more realistic estimates for mt-sDNA, FIT, and COL follow-up adherence has substantial impact on the predicted outcomes. Using reported adherence rates, rather than assuming 100% adherence, mt-sDNA yields greater CRC screening benefits vs FIT.Table 1.: Predicted life-years gained (LYG), colorectal cancer (CRC) incidence reduction, and CRC mortality reduction for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) in 3 different adherence scenarios per 1000 individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 yearsFigure 1.: Percent difference in predicted life-years gained (LYG) per 1000 individuals assuming 100% adherence for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) at assumed adherence rate intervals for follow-up colonoscopy (COL) in individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 years. White boxes indicate 10% positive difference with mt-sDNA versus FIT. Dark gray boxes indicate >10% negative difference with mt-sDNA versus FIT.Figure 2.: Percent difference in predicted life-years gained (LYG) per 1000 individuals by reported adherence rates for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) at assumed adherence rate intervals for follow-up colonoscopy (COL) in individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 years. White boxes indicate 10% positive difference with mt-sDNA versus FIT. Dark gray boxes indicate >10% negative difference with mt-sDNA versus FIT.

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