From concept to clinic: Implementation and early outcomes of MCED screening at RUSH Health System.

e13591 Background: Approximately one-third of Americans will develop cancer, yet guideline-recommended screening exists for only five cancer types, leaving many, including aggressive malignancies, without early detection options. Multi-cancer early detection (MCED) blood tests based on cell-free DNA methylation patterns offer a novel strategy to detect a shared cancer signal across multiple tumor types, including those without standard screening, with high specificity and a low false-positive rate. Here, we describe the implementation of an MCED test (Galleri) into routine care within the RUSH Health System. Methods: Over a 14-month period (May 2024–July 2025), RUSH Health System (Chicago, IL), encompassing three hospitals and over 2300 providers, developed an implementation model for MCED screening. Results: RUSH leveraged a centralized model for MCED implementation within the existing germline genetic high-risk screening program. In the months preceding and post-implementation, eight medical education sessions were delivered to 176 individuals in primary care, OB/GYN, and the laboratory. Three additional sessions post-implementation, educated 92 providers and stakeholders. In the model, patient activation could occur through (1) patient self-referral by completing an online intake form or (2) provider-driven for interested patients by a direct ordering pathway built into the electronic medical record (EMR). For negative MCED results ordered through the high-risk team, a phone call is made to all patients within 24 hours followed by written communication. For positive MCED tests within RUSH, providers can refer to the high-risk team to coordinate all diagnostic follow-up or order sets were built into the EMR for each cancer signal origin to guide providers in the diagnostic workup. Between July 2025 and January 2026, over 500 individuals were counseled on MCED screening, 422 orders were placed, and 303 screens were completed. Of the completed screens, the median age was 61 years and 58.5% were female. Most screens (n = 284, 92%) were ordered through the high-risk screening program: 84% patient self-referrals and 16% provider-driven referrals. The remaining 25 orders were placed directly by 11 providers outside of the high-risk screening program. Among those screened at RUSH to date, two received a positive MCED result, one of whom has been confirmed to have anal cancer and one whose workup is ongoing. Conclusions: This implementation and early data illustrate one approach by which a health system integrated MCED screening and is scaling adoption of a novel technology into clinical practice. The model facilitates access for interested patients while providing structured support for providers.