Should Multi-Cancer Early Detection Testing Replace Guideline-Recommended Colorectal Cancer Screening? A Comparative Modeling Analysis

Background Colorectal cancer (CRC) screening strategies such as colonoscopy and fecal immuno-chemical testing (FIT) reduce CRC mortality through both early detection and prevention via precursor lesion removal. Multicancer early detection (MCED) blood tests offer the potential to detect multiple cancers with a single assay but provide little opportunity for cancer prevention. Whether the ability to detect multiple cancers can offset the loss of CRC prevention remains unclear. Methods We used microsimulation to compare MCED and guideline-recommended CRC screening strategies. CRC outcomes were simulated using CRC-SPIN v3.0 and non-CRC cancers using MCEDsim, calibrated to SEER incidence data. Assuming optimistic MCED preclinical sensitivity equal to published case-control estimates, we compared life-years gained and late-stage disease outcomes for annual FIT, decennial colonoscopy, and MCED-only strategies across a range of preclinical durations and survival benefit assumptions. Results: Relative to no screening, colonoscopy and FIT reduced late-stage diagnoses by 26% and 25%, respectively, versus 20%-32% for annual MCED screening. Across assumptions, MCED-only strategies generated 33%-51% as many life-years gained as colonoscopy. Conclusions Currently available MCED tests are unlikely to be effective replacements for guideline-recommended CRC screening, which derives substantial benefit from the detection and removal of precursor lesions. MCED screening may provide additional benefit as a supplement to recommended CRC screening.