BACKGROUND: Multi-cancer early detection (MCED) next-generation-sequencing blood tests represent a potential paradigm shift in screening.

METHODS: We estimated the impact of screening in the US and UK. We used country-specific parameters for uptake, and testspecific sensitivity and false-positive rates for current screening: breast, colorectal, cervical and lung (US only) cancers. For the MCED test, we used cancer-specific sensitivities by stage. Outcomes included the true-positive:false-positive (TP:FP) ratio; and the cost of diagnostic investigations among screen positives, per cancer detected (Diagcost). Outcomes were estimated for recommended screening only, and then when giving the MCED test to anyone without cancer detected by current screening plus similarly aged adults ineligible for recommended screening.

RESULTS: In the US, current screening detects an estimated 189,498 breast, cervical, colorectal and lung cancers. An MCED test with 25–100% uptake detects an additional 105,526–422,105 cancers (multiple types). The estimated TP:FP (Diagcost) was 1.43 ($89,042) with current screening but only 1:1.8 ($7060) using an MCED test. For the UK the corresponding estimates were 1:18 (£10,452) for current screening, and 1:1.6 (£2175) using an MCED test.

CONCLUSIONS: Adding an MCED blood test to recommended screening can potentially be an efficient strategy. Ongoing randomised studies are required for full efficacy and cost-effectiveness evaluations.