Enterprise-wide implementation of multicancer detection testing across a large academic health system.

10578 Background: Multicancer detection (MCD) testing using cell-free DNA methylation patterns is a novel blood-based approach to cancer screening. In 2022, Mayo Clinic implemented offering MCD testing into routine clinical practice. Prior real-world reports have been limited to single-site experiences. We evaluated enterprise-wide implementation of MCD testing across all three Mayo Clinic sites using the Mayo Clinic Platform. Methods: We performed a retrospective analysis of de-identified clinical data from Mayo Clinic Platform Discover, including GRAIL Galleri tests performed at Mayo Clinic sites in Rochester, MN; Scottsdale, AZ; and Jacksonville, FL. This activity did not require IRB review per 45 CFR 46.102. Demographics, test results, cancer diagnoses, and prior cancer history were extracted using a privacy-preserving protocol, with data de-identified by expert determination. ICD-10 diagnostic codes were used to identify subsequent cancer diagnoses. Results: A total of 8,201 Galleri tests were performed in 7,300 patients; some patients underwent repeat testing. Fifty-seven tests (0.7%) were positive. Among MCD-positive patients, cancer diagnostic codes were identified in 32 patients, yielding a positive predictive value (PPV) of 58.7%. The most common cancers identified were oropharyngeal (34.4%), lymphoid and hematopoietic (34.4%), and gastrointestinal malignancies (18.8%).Among 8,144 MCD-negative tests (99.3% of all testing performed), 423 patients (5.2%) subsequently received a cancer diagnostic code, yielding a negative predictive value of 92.5%. The most commonly identified cancers in this group were male genital organs (36.6%), urinary tract (10.6%), and thyroid or other endocrine glands (7.3%). Overall, 10.1% of patients had a prior cancer history, which was more common in MCD-positive than MCD-negative patients (22.6% vs 10.0%). Patients with positive tests were older (mean age 68.4 vs 61.5 years) and more often male (67% vs 62%). Race distribution was similar. Conclusions: Enterprise-wide implementation of MCD testing across diverse clinical settings is feasible within routine workflows. Over half of positive tests were associated with cancer diagnostic codes, supporting the clinical promise of MCD testing. Limitations include incomplete capture of externally diagnosed cancers and lack of cancer signal-of-origin data. The Mayo Clinic Platform enables scalable, secure analytics to support future cancer interception strategies.