FIT and molecular tests versus colonoscopy: an economic evaluation of colorectal cancer screening in the United States.

Background: In 2021, the United States spent US$43.2 billion on five major cancer screenings, including US$27.5 billion for colorectal cancer (CRC). Colonoscopy screening (US$23.7 billion) accounting for 54.8% of total screening expenditures despite representing only 9.3% of initial tests. The high cost and resource intensity of colonoscopy as a primary CRC screening modality may constrain population-level implementation. Methods: We conducted a deterministic decision-analytic modeling study comparing five non-colonoscopy CRC screening strategies-fecal immunochemical test (FIT), two stool-based (Cologuard, ColoSense) and two blood-based (Shield, SimpleScreen) molecular tests-with initial colonoscopy screening in a simulated 2021 cohort of 9.2 million individuals. Positive non-colonoscopy results were assumed to trigger a follow-up colonoscopy. Primary analysis used an annual episode, a 10-year analysis estimated cumulative costs and colonoscopy demand based on intervals and adherence. Results: Clinical trial data demonstrated broadly similar CRC detection yield across five non-colonoscopy screening tests, however, blood-based tests showed limited ability to detect advanced precancerous lesions, whereas stool-based tests demonstrated superior performance. In the annual screening economic evaluation, colonoscopy detected 56,810 CRC cases and required 9.2 million procedures, with an average cost of US$2,571 per individual screened and a cost per CRC case detected of US$416,389. FIT detected 44,132 CRC cases, with a lower but directionally comparable yield to molecular tests (47,362-56,451 cases), required 298,544 follow-up colonoscopies, and had the lowest cost per individual screened (US$141) and per CRC case detected (US$29,318; 7.0% of colonoscopy). Replacing initial colonoscopy screening with FIT reduce total screening costs from US$23.7 billion to US$1.3 billion (94.5% reduction), saving US$22.4 billion. In the 10-year analysis, FIT remained the lowest-cost strategy (US$6.6 billion versus US$23.7 billion for initial colonoscopy) with substantially lower cumulative colonoscopy demand (1.5 million versus 9.2 million for initial colonoscopy). Stool-based molecular tests cost more than FIT (US$18.7-21.5 billion), and blood-based tests even higher than initial colonoscopy costs (US$42.1-42.4 billion) despite lower colonoscopy demand. Conclusions: Across both annual and 10-year cumulative analyses, these findings describe the short-term budgetary and resource implications of FIT-first CRC screening strategy, including reduced colonoscopy demand and screening expenditures while maintaining a broadly comparable CRC detection yield.