Assessment of the Impact of Multi-Cancer Early Detection Test Screening Intervals on Late-Stage Cancer at Diagnosis and Mortality Using a State-Transition Model

OBJECTIVE:Multi-cancer early detection (MCED) tests are novel technologies that detect cancer signals from a broad set of cancer types using a single blood sample. The objective of this study was to estimate the effect of screening with an MCED test at different intervals on cancer stage at diagnosis and mortality endpoints. DESIGN:The current model is based on a previously published state-transition model that estimated the outcomes of a screening programme using an MCED test when added to usual care for persons aged 50-79. Herein, we expand this analysis to model the time of cancer diagnosis and patient mortality with MCED screening undertaken using different screening schedules. Screening intervals between 6 months and 3 years, with emphasis on annual and biennial screening, were investigated for two sets of tumour growth rate scenarios: 'fast (dwell time=2-4 years in stage I) and 'fast aggressive' (dwell time=1-2 years in stage I), with decreasing dwell times for successive stages. SETTING:Inputs for the model include (1) published MCED performance measures from a large case-control study by cancer type and stage at diagnosis and (2) Surveillance, Epidemiology and End Results (SEER) data describing stage-specific incidence and cancer-specific survival for persons aged 50-79 in the US for all cancer incidence. OUTCOME MEASURES:We used the following outcome measures: diagnostic yield, stage shift, and mortality. RESULTS:Annual screening under the fast tumour growth scenario was associated with more favourable diagnostic yield. There were 370 more cancer signals detected/year/100,000 people screened, 49% fewer late-stage diagnoses, and 21% fewer deaths within 5 years than usual care. Biennial screening had a similar, but less substantial, impact (292 more cancer signals detected/year/100,000 people screened; 39% fewer late-stage diagnoses, and 17% fewer deaths within 5 years than usual care). Annual screening prevented more deaths within 5 years than biennial screening for the fast tumour growth scenario. However, biennial screening had a higher positive predictive value (54% vs 43%); it was also more efficient per 100,000 tests in preventing deaths within 5 years (132 vs 84), but prevented fewer deaths per year. CONCLUSION:Adding MCED test screening to usual care at any interval could improve patient outcomes. Annual MCED test screening provided more overall benefit than biennial screening. Modelling the sensitivity of outcomes to different MCED screening intervals can inform timescales for investigation in trials.