Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy

Abstract

Background & aims: Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (liquid biopsy) could improve screening participation.

Methods: Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMS_min) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses.

Results: CMS_min reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMS_min cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMS_min would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation.

Conclusions: CMS_min could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.

Keywords: Blood-Based Biomarker; Blood-Based Testing; Colorectal Cancer; Comparative Effectiveness; Cost-Effectiveness; Decision Analysis; Health Economics; Liquid Biopsy; Screening.

Figure 1.

Clinical outcomes with established CRC screening tests and with emerging blood-based biomarkers. The minimum thresholds set by CMS are 74% sensitivity and 90% specificity for CRC (CMS minimum). QALYs are discounted and they are from age 45 years.

Figure 2.

Discounted mean cost per person and QALYs per person with established CRC screening tests and with emerging blood-based biomarkers. The minimum thresholds set by the CMS are 74% sensitivity and 90% specificity for CRC (CMS minimum).

Figure 3.

Impact of sensitivity for APL on the effectiveness of a blood-based test performed every 3 years. Improving APL sensitivity had a much greater impact than improving CRC sensitivity. FIT screening is annual. Colonoscopy screening is every 10 years.