Abstract 7132: Estimated post-test probabilities of cancers for individuals receiving multi-cancer early detection (MCED) tests

Abstract Background: Individuals and their physicians receiving MCED tests may need to interpret the results they receive in the context of their particular cancer risks, both for positive (“cancer signal detected”) and for negative (“no cancer signal detected”) test results. Using estimated performance characteristics of an on-market MCED test we modeled post-test probabilities after receiving an MCED test result for a variety of typical populations stratified by five year age group and sex, and adjusted for smoking status (unadjusted, ever, former, never), as well as the duration of reduced cancer risk in those who tested negative. Methods: Using (1) 2006-2015 data (cancer incidence by age, sex) from the Surveillance, Epidemiology and End Reports (SEER) 17, (2) adjustments to incidence by smoking risk factors (3) test sensitivity from the third sub-study of the Circulating Cancer Genome Atlas, and (4) duration of detectable window from the American Cancer Society Cancer Prevention Study III and an exponential distribution for the detection window, we computed post-test probabilities of detection (for positive tests), and depletion of future cancers over various time intervals (for negative tests). Results: Individuals receiving a negative MCED test result had 42-56% (min-max) the level of late stage (III+IV) cancer diagnosis in the year following blood draw, rising to 72-82% the second year if they did not return for an annual test. Individuals receiving a positive MCED test result with a cancer-signal origin (CSO) returned, had a cancer at that signal location if cancer is confirmed (97% of individual-CSO combinations), with sufficient positive predictive value at each CSO justifying workup (97% of individual-CSO combinations) with few exceptions, such as a breast CSO in males. An important complicating factor is the utilization of conventional screening or imaging tests which can significantly alter the pre-test probability of having certain cancers, for which we provide the example of colonoscopy and its effects over the ten-years post-negative screen. Conclusions: For common clinical covariates of age, sex, and smoking status this model provides important clinical context for interpreting test reports, including the potential for a significant increase in late stage, deadly interval cancers when testing at longer intervals than one year. Following the CSO estimate in the majority of individuals with positive test results is justified by comparison to usual clinical decision thresholds. Citation Format: Candace Westgate, Christina Clarke Dur, Eric Klein, Alpa V. Patel, Earl Hubbell. Estimated post-test probabilities of cancers for individuals receiving multi-cancer early detection (MCED) tests [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7132.