Comparing the Cost-Effectiveness of Innovative Colorectal Cancer Screening Tests

Elisabeth F. P. Peterse, PhD; Reinier G. S. Meester, PhD; Lucie de Jonge, MSc; Amir-Houshang Omidvari, MD; Fernando Alarid-Escudero, PhD; Amy B. Knudsen, PhD; Ann G. Zauber, PhD; Iris Lansdorp-Vogelaar, PhD


J Natl Cancer Inst. 2021;113(2):154-161. 

In This Article

Abstract and Introduction


Background: Colorectal cancer (CRC) screening with colonoscopy and the fecal immunochemical test (FIT) is underused. Innovative tests could increase screening acceptance. This study determined which of the available alternatives is most promising from a cost-effectiveness perspective.

Methods: The previously validated Microsimulation Screening Analysis-Colon model was used to evaluate the cost-effectiveness of screening with capsule endoscopy every 5 or 10 years, computed tomographic colonography every 5 years, the multi-target stool DNA test every 1 or 3 years, and the methylated SEPT9 DNA plasma assay (mSEPT9) every 1 or 2 years. We also compared these strategies with annual FIT screening and colonoscopy screening every 10 years. Quality-adjusted life-years gained (QALYG), number of colonoscopies, and incremental cost-effectiveness ratios were projected. We assumed a willingness-to-pay threshold of $100 000 per QALYG.

Results: Among the alternative tests, computed tomographic colonography every 5 years, annual mSEPT9, and annual multi-target stool DNA screening had incremental cost-effectiveness ratios of $1092, $63 253, and $214 974 per QALYG, respectively. Other screening strategies were more costly and less effective than (a combination of) these 3. Under the assumption of perfect adherence, annual mSEPT9 screening resulted in more QALYG, CRC cases averted, and CRC deaths averted than annual FIT screening but led to a high rate of colonoscopy referral (51% after 3 years, 69% after 5 years). The alternative tests were not cost-effective compared with FIT and colonoscopy.

Conclusions: This study suggests that for individuals not willing to participate in FIT or colonoscopy screening, mSEPT9 is the test of choice if the high colonoscopy referral rate is acceptable to them.


Colorectal cancer (CRC) is a leading cause of cancer death in the United States, with an estimated 53 000 associated deaths in 2020.[1] CRC screening can prevent CRC death through earlier detection or through removal of premalignant polyps[2,3] and is recommended by the US Preventive Services Task Force from age 50 years to 75 years[4] and by the American Cancer Society (ACS) from age 45 years to 75 years.[5] Despite the effectiveness of screening, almost 40% of 50- to 75-year-olds reported not having received guideline-consistent CRC screening. Important barriers for screening include fear and disgust of the screening test.[6,7] Therefore, new tests that circumvent these barriers are needed to increase screening participation.

Fecal occult blood testing and colonoscopy were already proposed as CRC screening tests in the late 1960s.[8,9] More recently developed US Food and Drug Administration (FDA)-approved tests are capsule endoscopy, specifically the PillCam COLON 2 (PillCam); the computed tomographic colonography (CTC); the multitarget stool DNA test (mtSDNA), also known as Cologuard (Exact Sciences Corporation, Madison, Wisconsin); and the methylated SEPT9 DNA plasma assay (mSEPT9), also known as the Epi proColon (Epigenomics AG). All these tests require colonoscopy follow-up of individuals with a positive test result. Several studies have suggested that these alternative tests are not cost-effective compared with colonoscopy or fecal immunochemical test (FIT) screening.[10–16] However, these tests have potential to attract the population not currently participating in screening. The mSEPT9 requires a blood sample, which may be preferred for some patients over collecting a stool sample or a more invasive test. The CTC, PillCam, and mtSDNA all have better test sensitivities than FIT while being less invasive than colonoscopy. Therefore, it is important to evaluate which of these alternative tests should be offered to individuals who are not willing to participate in FIT or colonoscopy screening. No study to our knowledge has compared all of these alternative screening tests in terms of cost-effectiveness. Therefore, in this study, the Microsimulation Screening Analysis-Colon (MISCAN-Colon) model was used to evaluate the comparative cost-effectiveness of the PillCam, the CTC, the mtSDNA, and the mSEPT9.