Virginia Cancer Screening Research Network Access Hub (Virginia CSRN Hub) - This application is being submitted in response to the NOSI identified as NOT-CA-24-111. This Administrative Supplement will expand recruitment from 1600 patients to 2000 patients as requested by National Cancer Institute (NCI) and address the newly identified costs of workup for positive multi-cancer detection tests (MCDs). Efforts will occur in the Virginia Hub for the National Cancer Screening Research Network (CSRN), a national network capable of conducting clinical trials and longitudinal studies, a central Statistics and Data Management Center, and a central Coordinating and Communication Center. Our Virginia CSRN ACCESS Hub was created from long-standing, inter-institutional partnerships to assist in this important national effort. These partnerships include 1) three health systems – Virginia Commonwealth University (VCU) Health, Inova Health System, and Sentara Healthcare; 2) one medical school – VCU; 3) two cancer centers – the Massey Comprehensive Cancer Center at VCU, an NCI-designated comprehensive cancer center, and the Inova Health’s Schar Cancer Institute which includes a recently launched Saville Cancer Screening and Prevention Center; 4) the NIH-funded Wright Regional Center for Clinical and Translational Science; and 5) a state-wide, primary care practice-based research network (Virginia Ambulatory Care Outcomes Research Network – ACORN). These entities have an established track record of working together for decades; collectively care for a sizable proportion of state residents including the largest safety net health system providing both urban and rural services to a majority of Virginia’s communities; demonstrated expertise in recruiting and retaining marginalized and underserved patients and communities in trials; and national expertise in cancer prevention, informatics, community engagement, and dissemination and implementation science. We proposed that the Virginia CSRN ACCESS Hub would initially recruit and retain at least 1,600 participants in the NCI- coordinated, three-arm randomized controlled Vanguard study to test two novel multi- cancer detection (MCD) tests compared to usual cancer screening care. NCI has requested this to be expanded to 2,000 participants. We will measure success by equitable and inclusive recruitment, timeliness and adherence to the diagnostic workup and treatment protocols, and participation in all national CSRN efforts. Additionally, we will conduct a novel, mixed methods analysis of our work using a consolidated framework for implementation research constructures to demonstrate our hub’s feasibility and sustainability for future CSRN trials and to assess factors necessary for widespread adoption of MCD tests, if proven effective. Our hub will meaningfully contribute to the Vanguard study and will bring unique partnerships, an equity lens, and dissemination and implementation expertise to the broader CSRN effort.