Blood-Based Colorectal Cancer Screening Projected to Fall Short Compared to FIT, Colonoscopy

David Lieberman, MD

Credit: Gastroenterology

Results from a trio of microsimulation models projected a blood-based screening test with a sensitivity of ≥ 74% for the detection of colorectal cancer (CRC) and a specificity of ≥ 90% would not be cost-effective compared with established screening strategies, despite meeting Centers for Medicare and Medicaid Services coverage criteria for such a test.¹

Although findings showed blood-based screening was cost-effective in an otherwise unscreened population, this was not the case compared to annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay (sDNA-FIT), and colonoscopy screening every 10 years – even with greater screening uptake, blood-based screening resulted in greater costs and a loss of benefit.¹

Whereas CRC was the fourth-leading cause of cancer death in both men and women < 50 years of age in the late 1990s, it has jumped to first in men and second in women.² Although the US Centers for Disease Control and Prevention highlights the potential benefit of several lifestyle modifications for reducing the risk of CRC, it also recognizes screening starting at 45 years of age as the most effective risk management strategy.³

“Despite the effectiveness and availability of screening, adherence to screening recommendations remains suboptimal at about 60%. There are persistent barriers to screening that include fear of and aversion to the screening test,” Rosita van den Puttelaar, PhD candidate at Erasmus MC in the Netherlands, and colleagues wrote.¹ “Emerging tests, such as a blood-based CRC screening test, have the potential to circumvent these barriers and increase screening participation.”

To evaluate the effectiveness and cost-effectiveness of a hypothetical blood-based CRC screening test meeting the Centers for Medicare and Medicaid Services coverage criteria, investigators used 3 microsimulation models to project the lifetime costs and quality-adjusted life-years (QALYs) and compared results for a blood-based test to those of no screening, FIT, sDNA-FIT, and colonoscopy every 10 years in a hypothetical cohort of 10 million average-risk individuals 45-75 years of age. Investigators noted the models (MISCAN-Colon, CRC-SPIN, and SimCRC) are part of the US National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network and have been used to inform past screening recommendations.¹

The current study used the same model input parameters and assumptions used in modeling analyses for the US Preventive Services Task Force in support of its 2021 recommendations for CRC screening. Costs of screening, screening-related complications, and cancer care were computed from a health care sector perspective and included reimbursed as well as out-of-pocket payments. A blood test was assumed to cost $500 per test, and its performance characteristics were based on Centers for Medicare and Medicaid Services coverage criteria.¹

Investigators calculated incremental cost-effectiveness ratios with effectiveness expressed in terms of the number of QALYs gained. A strategy was considered cost-effective if the incremental cost-effectiveness ratio was below the willingness-to-pay (WTP) threshold of $100,000 per QALY gained. The main outcomes were computed per 1000 45-year-old individuals.¹

Without screening, the models predicted 77–88 CRC cases and 32–36 CRC deaths per 1000 individuals, costing $5.3–$5.8 million. Compared with no screening, blood-based screening increased the number of QALYs by 83–116 per 1000 and costs by $3.0–$3.8 million per 1000. With an incremental cost of $25,600–$43,700 per QALY gained, investigators determined blood-based screening was cost-effective compared to no screening.¹

However, compared to FIT, sDNA-FIT, and colonoscopy screening, blood-based screening was not cost-effective. Compared to FIT screening, blood-based screening resulted in 39–68 fewer QALYs per 1000 while increasing costs by $4.0–$4.8 million. Compared to sDNA-FIT, blood-based screening resulted in 26–59 fewer QALYs per 1000 and increased costs by $1.3–$2.1 million. Compared to colonoscopy screening, blood-based screening resulted in 45–84 fewer QALYs while also increasing costs by $2.3–$3.4 million.¹

In a sensitivity analysis where uptake of blood-based screening was 20% greater than uptake of FIT or colonoscopy screening, blood-based screening meeting Centers for Medicare and Medicaid Services performance criteria was still estimated to result in lower QALYs and higher costs, with 5–24 QALYs lost and a cost increase of $3.2–$3.5 million compared to FIT and 10–34 QALYs lost with a cost increase of $2.2–$2.6 compared to colonoscopy.¹

In 1.6%–10.0% and 0.1%–0.5% of the simulations in probabilistic sensitivity analyses, blood-based screening was cost-effective compared to sDNA-FIT and colonoscopy screening, respectively, but was never cost-effective compared to FIT. At higher WTPs, the probability that blood-based screening was cost-effective compared to FIT, sDNA-FIT, and colonoscopy increased, but even at a WTP of $150,000, blood-based screening was rarely cost-effective compared to FIT (0%–1.1%).¹

Investigators highlighted 3 key limitations to these findings, including the assumption of independence between repeat blood tests despite the unknown degree of independence, assumed equivalence of disutility associated with a blood-based screening test and FIT, as well as a lack of consideration for any substitution effect.¹

“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective or cost-effective, and would worsen outcomes,” study investigator David Lieberman, MD, said in a press release.⁴

References:

1. ^{van den Puttelaar R, de Lima PN, Knudsen AB, et al. Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With a Blood Test That Meets the Centers for Medicare & Medicaid Services Coverage Decision. Gastroenterology. https://doi.org/10.1053/j.gastro.2024.02.012}
2. ^{Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. American Cancer Society. https://doi.org/10.3322/caac.21820}
3. ^{US Centers for Disease Control and Prevention. What Can I Do to Reduce My Risk of Colorectal Cancer? Colorectal Cancer. February 23, 2023. Accessed March 25, 2024. https://www.cdc.gov/cancer/colorectal/basic_info/prevention.htm}
4. ^{American Gastroenterological Association. New data offer reality check on blood-based colorectal cancer screening. EurekAlert! March 26, 2024. Accessed March 26, 2024. https://www.eurekalert.org/news-releases/1038731}