OBJECTIVES: Colorectal cancer (CRC) is a major cause of cancer-related deaths globally. Two innovative stool-based CRC screening technologies (mt-sRNA and mt-sDNA 2.0) have recently emerged. This study evaluated the cost-effectiveness of these innovative stool-based CRC screening tests compared to previously approved stool-based CRC screening methods (FIT, HS-gFOBT and mt-sDNA) from a US payer’s perspective.

METHODS: A Markov model simulated clinical and economic outcomes for a hypothetical cohort of 45-year-olds at average CRC risk over their lifetime. Nine screening strategies were evaluated: (1) annual FIT; (2) annual HS‐gFOBT; (3) mt-sDNA every 3 years; (4) annual mt-sDNA; (5) mt-sRNA every 3 years; (6) annual mt-sRNA; (7) mt-sDNA 2.0 every 3 years; (8) annual mt-sDNA 2.0; (9) no screening. Primary outputs included CRC cases, deaths, direct medical costs, and quality-adjusted life-years (QALYs). Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Sensitivity analyses examined the robustness of findings.

RESULTS: Comparing each strategy to the next less costly option, 6 of 9 strategies were dominated and eliminated from further cost-effectiveness analysis. Annual mt-sDNA 2.0 gained the highest QALYs (21.58 QALYs), followed by annual FIT (21.56 QALYs) and no screening (21.42 QALYs). The ICER of annual mt-sDNA 2.0 versus annual FIT was US$463,088/QALY, exceeded the willingness-to-pay (WTP) of US$10,000/QALY. Annual FIT emerged as the preferred strategy with an ICER of US$952/QALY. Annual HS-gFOBT became the preferred cost-effective strategy when the sensitivity of FIT was below 21.3% or the specificity of HS-gFOBT exceeded 94.2% in the one-way sensitivity analysis. In probabilistic analysis, the probabilities to be preferred cost-effective option (at WTP US$100,000/QALY) were 84.37% for annual FIT, 15.63% for annual HS-gFOBT and 0% for other screening strategies.

CONCLUSIONS: Annual FIT appared to be the preferred strategy and the cost-effectiveness is subject to the sensitivity of FIT for advanced adenomas and the specificity of HS-gFOBT.