Net Results Vary When Using Cell-Free DNA Blood Tests for CRC Screening

The usefulness of the cell-free DNA blood test (cf-bDNA) can vary based on the reasons for using the method of screening for colorectal cancer (CRC). According to a new study published in Annals of Internal Medicine,¹ the balance between achieving screening in those who may otherwise not do so and patients declining more effective alternatives in favor of cf-bDNA could determine if it is a net benefit or causes harm.

CRC incidence and mortality can be decreased through regular screening, which begins at the age of 45 years, according to guidelines published by the US Preventive Services Task Force. But even with the recommendations for early screening, many patients in the US are not up to date on the screening. This has led to the development of tests that could make it easier to access screening, including fecal immunochemical tests (FIT). The cf-bDNA test was FDA approved in July 2024,² and has high sensitivity for stages II to IV. However, there could be tradeoffs with the use of this test and other types of tests, as some are unsure how blood tests may compare with more tried and true methods of screening.³ This study aimed to project the reductions in incidence and mortality for CRC as well as its cost-effectiveness with emerging screening tests for CRC that are blood-based and stool-based.

The researchers used the Model of Screening and Surveillance for Colorectal Cancer (MOSAIC) for this analysis on cost effectiveness and probabilistic decision. The comparators used were colonoscopy performed every 10 years, FIT performed yearly, and multitarget stool DNA test (MT-sDNA) performed every 3 years. The novel tests evaluated in this analysis were the FIT-RNA performed every 3 years and the cf-bDNA performed every 3 years based on coverage by CMS. Cases and deaths in CRC, quality adjusted life years (QALYs), costs, and number of colonoscopies in hypothetical groups of 100,000 individuals starting aged 45 years were the principal model outputs. The idealized screening implementation acted as the base case, which included 100% uptake.

Although the new blood test is better than no screening, FIT and colonoscopies may remain the standard for screening for CRC | Image credit: angellodeco - stock.adobe.com

There were 7470 (95% uncertainty interval [UI], 6606-8322) cases of CRC and 3624 (95% UI, 3211-4030) deaths due to CRC that occurred in a cohort of 100,000 individuals without screening beginning at 45 years of age. Incidence of CRC was reduced by more than 70% in both colonoscopy (RR, 0.21; 95% UI, 0.19-0.22) and FIT (RR, 0.29; 95% UI, 0.27-0.31) assuming 100% participation in all steps. Mortality was also reduced by 75% or more in both colonoscopy (RR, 0.19; 95% UI, 0.17-0.20) and FIT (RR, 0.25; 95% UI, 0.23-0.27) compared with no screening.

MT-sDNA testing boasted a reduction of incidence (RR, 0.32; 95% UI, 0.30-0.34) and mortality (RR, 0.27; 95% UI, 0.25-0.29) by 68% and 73% respectively when compared with no screening; FIT-RNA had similar results. Incidence and mortality were reduced by 42% (RR, 0.58; 95% UI, 0.55-0.61) and 56% (RR, 0.44; 95% UI, 0.42-0.47) when using cf-bDNA compared with no screening.

The MT-sDNA test cost $6300 (95% UI, $1100-$11,800) per QALY gained compared with no screening; cf-bDNA cost $89,600 (95% UI, $74,800-$102,300) per QALY gained compared with no screening. FIT and colonoscopy were more effective and less costly compared with no screening, cf-bDNA, and MT-sDNA. If cf-bDNA was the same price as MT-sDNA, it would still be less effective and more costly compared with FIT or colonoscopy. When looking at shorter screening intervals, RRs decreased for both incidence and mortality as interval times decreased when compared with no screening but costs remained high.

Should colonoscopy follow-up rates be comparable, uptake of cf-bDNA every 3 years would have to be 1.70-fold that of yearly FIT if it was to match the effect of FIT on incidence of CRC, 1.35-fold to match FIT’s effect on mortality, and 1.32-fold to match FIT’s effect on quality-adjusted life expectancy.

There were some limitations to this study. Independent test results were assumed from round to round but could be affected by lesions being missed by a test. The trials of cf-bDNA were not powered to detect differences in sensitivity by the stage of CRC but early results show a low sensitivity for stage I CRC.

The researchers concluded that cf-bDNA testing can help to reduce the mortality and incidence of CRC when compared with not performing screening at all but the cost and efficacy are still unfavorable when compared with colonoscopies and FIT. The benefit of cf-bDNA may be in its ability to bring people into screening who may not have otherwise screened but those who are already receiving stool tests and colonoscopies should remain using those tests rather than switching to cf-bDNA tests.

References

1. Ladabaum U, Mannalithara A, Schoen RE, Dominitiz JA, Lieberman D. Projected impact and cost-effectiveness of novel molecular blood-based or stool-based screening tests for colorectal cancer. Ann Intern Med. Published online October 29, 2024. doi:10.7326/ANNALS-24-00910.
2. Bonavitacola J. Blood test approved by FDA for screening for colorectal cancer. The American Journal of Managed Care^® (AJMC^®). July 29, 2024. Accessed October 29, 2024. https://www.ajmc.com/view/blood-test-approved-by-fda-for-screening-for-colorectal-cancer
3. Bonavitacola J. The benefits and risks of using liquid biopsy for CRC screening. AJMC. August 15, 2024. Accessed October 29, 2024. https://www.ajmc.com/view/the-benefits-and-risks-of-using-liquid-biopsy-for-crc-screening