Modeled sensitivity to detect preclinical cancers by a multi-cancer early detection test in a retrospective study

Music City Center 

In a retrospective analysis of the American Cancer Society Cancer Prevention Study-3 (CPS-3) cohort, GRAIL's multicancer early detection (MCED) test was evaluated for detectability in stored plasma samples collected before cancer diagnosis. In the present work, classical state-transition models were adapted to characterize the natural history of ctDNA-shedding cancers. The terminology of sensitivity for detecting preclinical cancers was discussed in the context of retrospective testing, and a novel Bayesian likelihood method was developed to estimate sensitivity and preclinical duration at early stage (localized and regional) and late stage (distant). We isolated certain state transition and sensitivity assumptions that were not directly testable in retrospective studies. Despite limitations of stored plasma samples, Bayesian analysis of the CPS-3 retrospective data showed that among the twelve prespecified cancers that represent two-thirds of cancer deaths in the United States, the test showed 61% estimated overall sensitivity, 43% estimated sensitivity for early-stage cancer, and 1.4-year average duration of preclinical detectability at early stage. With the limitation of a non-interventional study and untestable modeling assumptions, these results are consistent with the potential of GRAIL's MCED test to detect cancers early in the preclinical phase.

Cancer Screening

Sensitivity