The Vanguard study: An NCI cancer screening research network multi-cancer detection feasibility study.

e22522 Background: Multi-cancer detection (MCD) tests are promising; however, large-scale trials are needed to establish their harms, benefits, and clinical utility. The NCI has established the Cancer Screening Research Network (CSRN) to evaluate novel screening technologies. The first study of CSRN, the Vanguard study, is designed to establish the feasibility of recruiting individuals from diverse backgrounds into randomized cancer screening trials and to evaluate trial design and diagnostic evaluation processes. Methods: The Vanguard study is a randomized, three-arm trial of two novel MCD assays and a usual care group (n = 24,000). Adults ages 45-75 without cancer in the last 5 years will be eligible. The primary outcomes are feasibility and equitable recruitment. Recruitment sites include nine US Hubs (“ACCESS Hubs”) selected for ability to recruit racially, ethnically, geographically and socioeconomically diverse participants. Participants randomized to an intervention arm will receive an MCD test at baseline and year 1 follow-up. MCD platforms selected for investigation demonstrate ability to screen for lung, breast, colorectal, prostate, bladder, ovarian, pancreatic, esophageal, liver and gastric cancers. All participants will provide blood samples and complete questionnaires centered around demographics, social determinants of health, cancer risk and screening history, anxiety, and cancer worry, at baseline and year 1. Year 2 will include the same questionnaires without a blood sample. All participants will be encouraged to participate in standard-of-care (SOC) cancer screenings. Those with abnormal MCD results will undergo a cancer site-specific, protocol-guided diagnostic evaluation. will be followed for SOC screening behavior, cancer incidence, mortality, and quality of life. Results: The Vanguard study protocol, developed in partnership between the CSRN Communications and Coordinating Center, Statistics and Data Management Center, ACCESS Hubs, and the NCI, will be launched in 2025. ACCESS Hubs will accrue participants over a two-year period. Several unique design elements have been integrated into this study: 1) Facilitation of recruitment and retention of underrepresented and rural populations using features such as remote consenting, remote blood collection, electronic surveys. 2) Results of a positive MCD will always be returned to participants but participants in 4 Hubs will be blinded to whether they have undergone testing with an MCD. 3) Results of MCD testing will identify a likely tissue of origin (e.g., ovary or pancreas) to guide diagnostic workup. Conclusions: The Vanguard study is a critical step to ensure rigorous design and implementation of future large RCTs evaluating the clinical efficacy and safety of MCDs. Results from this study will inform a larger RCT to evaluate whether MCDs are beneficial in detecting cancer early, and any potential harms of the tests.