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Multi-cancer early detection (MCED) tests offer to screen for multiple typesof cancer with a single blood sample. Despite their promising diagnosticperformance, evidence regarding their population benefit is not yet available.Expecting that benefit will derive from detecting cancer before it progressesto an advanced stage, we develop a general two-stage model to project thereduction in advanced-stage diagnoses given stage-specific test sensitivitiesand testing ages. The model can be estimated using cancer registry data andvalues for the mean overall and advanced-stage preclinical sojourn times. Wefirst estimate the model for lung cancer and validate it against the stageshift observed in the National Lung Screening Trial. We then estimate the modelfor liver, pancreas, and bladder cancer, which have no recommended screeningtests, and we project stage shifts under a shared MCED testing protocol. Ourframework transparently integrates available data to project reductions inadvanced-stage diagnoses due to MCED testing.

A general two-stage progressive model of cancer natural history to project downstaging due to multi-cancer screening tests