Comparison of Simulated Outcomes Between Stool- and Blood-Based Colorectal Cancer Screening Tests

Abstract

Objectives: The Centers for Medicare & Medicaid Services (CMS) recommends covering blood-based tests meeting proposed minimum performance thresholds for colorectal cancer (CRC) screening. Outcomes were compared between currently available stool-based screening tests and a hypothetical blood-based test meeting CMS minimum thresholds. Methods: Using the CRC-AIM model, outcomes were simulated for average-risk individuals screened between ages 45-75 years with triennial multi-target stool DNA (mt-sDNA), annual fecal immunochemical test (FIT), and annual fecal occult blood test (FOBT). Per CMS guidance, blood-based CRC screening was modeled triennially, with 74% CRC sensitivity and 90% specificity. Although not specified by CMS, adenoma sensitivity was set between 10-20%. Published adenoma and CRC sensitivity and specificity were used for stool-based tests. Adherence was set at (a) 100%, (b) 30-70%, in 10% increments, and (c) real-world rates for stool-based tests (mt-sDNA=65.6%; FIT=42.6%; FOBT=34.4%). Results: Assuming perfect adherence, a blood-based test produced ≥19 lower LYG than stool-based strategies. At the best-case scenario for blood-based tests (100% adherence and 20% adenoma sensitivity), mt-sDNA at real-world adherence achieved more LYG (287.2 vs 297.1, respectively) with 14% fewer colonoscopies. At 100% blood-based test adherence and real-world mt-sDNA and FIT adherence, the blood-based test would require advanced adenoma sensitivity of 30% to reach the LYG of mt-sDNA (297.1) and approximately 15% sensitivity to reach the LYG of FIT (258.9). Conclusions: This model suggests that blood-based tests with CMS minimally-acceptable CRC sensitivity and low advanced adenoma sensitivity will frequently yield inferior outcomes to stool-based testing across a wide range of adherence assumptions.