Katherine A Guthrie, Garnet L Anderson, Ari Bell-Brown, Linda S Cook, Mark P Doescher, Ruth B Etzioni, Ziding Feng, Louise M Henderson, James Herman, Stacey A Honda, Aimee S James, Rebecca Kaltman, Charles Kooperberg, Alex H Krist, Carrie B Lee, Jeffrey K Lee, Elyse LeeVan, Joseph C Liao, Lori M Minasian, Kathleen N Moore, Patrick Nana-Sinkam, Kristen E Natale, Christine Neslund-Dudas, Quyen Ngo-Metzger, Mary Jane C Ong, Caryn E S Oshiro, Yikyung Park, Christos Patriotis, Paul Pinsky, Philip C Prorok, Daniel S Reuland, Debra P Ritzwoller, Wendy S Rubinstein, Lori C Sakoda, John Sayles, Jeannette M Schenk, Scott Shofer, Michael Simoff, Adetunji T Toriola, Larissa White, Emily S Wion, Marie Wood, Scott D Ramsey
A new generation of cancer screening tests, Multi-Cancer Detection (MCD) tests, aims to advance cancer early detection. MCD tests combine blood-based assays of biological components and bioinformatics algorithms to simultaneously detect multiple types of cancer. If shown to improve health outcomes, these new technologies would be simple to implement, improving accessibility and uptake. Importantly, MCD tests offer early detection opportunities for cancers with no established screening modalities. Despite their promise, evidence supporting public health benefits of MCD tests for early detection benefits is lacking. No consensus yet exists for determining the level of screening performance or the effects on cancer outcomes needed to recommend adoption. Further, the potential harms of screening (e.g., unnecessary procedures, increased anxiety and cancer worry) are often overlooked. To address the need for objective evaluation of novel screening methods, the National Cancer Institute created the Cancer Screening Research Network (CSRN). The CSRN mission is to implement rigorous clinical trials to evaluate a broad range of technologies and approaches for cancer screening. The CSRN Vanguard Study is the first US randomized trial of MCDs. The study will develop and determine the feasibility of critical protocol components of a subsequent full-scale trial to evaluate MCD tests. The study will enroll 18,000-24,000 participants aged 45-75 years without known cancer and randomize them into one of 3 arms: two separate intervention arms each evaluating one MCD test, or a control arm. Information gained will inform full-scale trial design and implementation features. ClinicalTrials.gov Identifier: NCT06995898; https://clinicaltrials.gov/study/NCT06995898; registered May 29, 2025.