Blood-Based CRC Screening Should Be Used Solely as Secondary Option

People who are not completing endorsed screening options for colorectal cancer (CRC) can be offered screening tests that are blood based, but only as a secondary option, according to a new study published in the Journal of Medical Economics.¹ The study, coauthored by The American Journal of Managed Care^®’s co–editor in chief, A. Mark Fendrick, MD, found that screening based on blood tests is more expensive and does not have comparable diagnostic accuracy.

The United States Preventive Services Task Force (USPSTF) recommends that screening for CRC be conducted between the ages of 45 and 75 in people living in the United States who are at average risk of the disease, with new tests becoming available to supplement colonoscopies, such as stool and blood tests.² However, adherence to this screening has not been as high as recommended. Adherence could be improved through testing that does not take as much prep time and are more accessible to patients, such as stool tests and blood tests.² However, blood tests have had mixed results both in diagnostic accuracy and in adherence.

This study aimed to use a simulation model to predict the clinical and economic implications of using blood tests to help improve screening for CRC.

Colorectal screening questionnaire | Image credit: Richelle - stock.adobe.com

This study used the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) to conduct the research. The microsimulation model helps to estimate outcomes by assessing the effect of interventions. The natural history of CRC, or the progression of CRC from the adenoma-carcinoma pathway, and screening components were both taken into account. The model simulated a US cohort of 2 million individuals at average risk of CRC who received either a blood test or a multi-target stool DNA (mt-sDNA) test.

The model took assumed adherence to mt-sDNA based on real-world data that suggested a 65.6% adherence. Blood-based tests do not have a published adherence rate, which led to several adherence levels being considered between 65.6% and 100%. Adherence for follow-up colonoscopies were assumed to be 100%. All costs were reported in US dollars, with mt-sDNA tests assumed to be $508.87 and blood-based tests assumed to be $895 based on CMS and manufacturer reports, respectively.

Life-years gained (LYG), number of cases and deaths averted through screening, LYG from a colonoscopy, and LYG from detection of CRC or adenoma were used as clinical outcomes of the study. Each person who had extended life years was evaluated further to determine LYG.

The simulation showed greater LYG and reduced cases and deaths due to CRC with mt-sDNA testing compared with blood-based testing. The mt-sDNA test was associated with 30% more LYG, 52% of cases of CRC avoided, and 32% of deaths due to CRC avoided when the adherence to mt-sDNA was 65.6% compared with 100% adherence to the blood-based test.

The triennial blood-based test was also not as effective as the mt-sDNA test, as triennial mt-sDNA led to 31% to 41% more LYG and 12% to 14% more LYG per colonoscopy when blood-based test adherence ranged from 65.5% to relatively 40% higher. Cases of CRC were also averted 57% to 72% more frequently, and deaths related to CRC were 35% to 45% more averted. A total of 64% to 67% of the LYG were in blood-based tests compared with 83% of the LYG when using mt-sDNA tests.

mt-sDNA tests were also more cost-effective due to being the more effective test and costing less. There was no price at which the triennial blood-based test was more cost-effective than the mt-sDNA test at a willingness-to-pay threshold of $50,000, $100,000 or $150,000. The blood-based test cost ranged from $185,877 to $206,510 for averting cases and from $277,162 to $295,469 for averting deaths.

There were some limitations to this study. Only 1 non-invasive test was used for comparison in this study, even though there are multiple non-invasive and invasive methods of screening for CRC that have been approved in the United States. The impact on intermittent and longitudinal adherence on cost-effectiveness was not looked into for this study. The inputs were based on a limited number of resources, and both Medicare and commercial insurers were assumed to price the blood-based test the same, which may not be true. This study also focused on 1 blood-based test, which could exclude other tests that have different performances.

"Access to multiple CRC screening options provides flexibility to accommodate patient preferences and drive greater engagement, consistent with the well-established perspective adopted by groups such as the USPSTF that the 'best test is the one that gets done,'" the authors wrote.

The researchers concluded that, although various ways of testing add flexibility in screening for CRC, there are tests that are better than others. Whereas blood-based tests were better than no testing, they were inferior to that of stool-based screening, such as mt-sDNA, in both efficacy and in cost.

"With the reported screening sensitivity for precancer detection, blood-based screening is projected to adversely impact the achievable benefits and burdens of CRC screening if these tests are used as a substitute for existing, higher performing test options," the authors concluded. "Thus, results from this study support application of blood-based tests only as a secondary option for patients who are not completing endorsed screening strategies, suggesting modification of the above statement to reflect that the 'best test is the one that gets done appropriately.'"

"It is important to remind those people eligible for CRC screening that those modalities receiving an A or B rating by the USPSTF must be covered without patient cost-sharing. In contrast, coverage for blood-based tests that have yet to be evaluated by the USPSTF is uncertain and likely will vary among plan types. Also, patients’ out of pocket costs are expected to be substantially higher than the zero cost-sharing amount for USPSTF-recommended CRC screening modalities," said Fendrick. "Given the clinical superiority of mt-sDNA and lower patient costs, these new blood based screening tests should be reserved only for those individuals eligible for screening who refuse all of the USPSTF recommended options.”

References

1. Kisiel JB, Fendrick AM, Ebner DW, et al. Estimated impact and value of blood-based colorectal cancer screening at varied adherence compared with stool-based screening. J Med Econ. Published online April 30, 2024. doi:10.1080/13696998.2024.2349467
2. Fendrick AM, Bagley N, Bonavitacola J. Michigan professors offer insights into what Braidwood ruling could mean for preventive screening in cancer care. Evidence Based Oncology. 2023;29(5):SP353-SP354.