Abstract Introduction The Connect for Cancer Prevention study is a new prospective cohort with repeated exposure assessment and long-term follow-up with the goals to study cancer initiation, multi-step carcinogenesis, early detection, and outcomes in a US study population. Over 85,000 participants have been recruited so far at 10 U.S. integrated healthcare systems. Biospecimens are a critical component to achieve Connect’s goals. Designing biospecimen collections in prospective cohort studies needs to balance the desire for large, repeated collections of various biospecimens with participant burden and cost. Methods The biospecimen collection protocol was informed by literature review, expert consultations, and pilot studies evaluating the effect of pre-analytical factors on commonly measured biomarkers. Baseline biospecimen collection includes a blood draw with serum, plasma, cell-free DNA collection tubes, a urine collection, and a mouthwash sample. Biospecimen collection is performed at over 50 collection locations, including within the clinical phlebotomy infrastructure and dedicated research laboratories. All biospecimens are shipped to a NCI central laboratory for processing and long-term storage. Process metrics include sample completeness, sample deviations, temperature logging, and needle-to-processing time, among others. Repeated biospecimen collections to study different exposure windows and biomarker changes within individuals are planned every three years, with more frequent collections among participants age 50 and older to pursue cancer early detection aims. Results As of October 2025, 56,445 participants of 81,030 enrolled (70%) donated blood and urine samples, with additional collections underway. We observed higher proportions of biospecimen donations in older age groups, ranging from 56% among participants age 30-34 to 83% among 66-70 year olds. Biospecimen collection participation was similar by sex and race/ethnicity. Among the collections, 60% were from clinical sites, and 40% from research laboratories. 82% of biospecimens collected at research laboratories were received at NCI within one day, and over 95% of all biospecimens were received within 4 days. The return of home-collected mouthwash samples was 77% among those sent a kit. Among 422,000 biospecimen tubes collected, 94% were complete with no deviations recorded. Over 90% of participants submitted a short survey at the time or shortly after biospecimen collection. Conclusions The Connect Cohort for Cancer Prevention combines electronic health record data, state-of-the-art surveys, and repeated biospecimen collections to address critical questions on cancer etiology and prevention. We successfully implemented a robust and efficient biospecimen collection approach at 10 recruitment sites across the U.S. Citation Format: Nicolas A. Wentzensen, Stephanie J. Weinstein, Amanda Black, Erin Schwartz, Hannah P. Yang, Michelle Brotzman, Paul Albert, Laura E. Beane Freeman, Amy Berrington de Gonzalez, Jonas S. Almeida, Jonine Figueroa, Montserrat García-Closas, Nicole Gerlanc, Gretchen L. Gierach, Rena Jones, Peter Kraft, Autumn Hullings, Charles E. Matthews, Habibul Ahsan, Brisa Aschebrook-Kilfoy, Chun-Hung Chan, Robert Greenlee, Stacey Honda, Benjamin A. Rybicki, Blythe Ryerson, Katherine Sanchez, Mark A. Schmidt, Kevin Skyes, Larissa L. White, Jeanette Ziegenfuss, Stephen J. Chanock, Christian C. Abnet, Mia M. Gaudet. Biospecimen collections for cancer etiology and prevention research in the Connect for Cancer Prevention Study: Guiding principles, approach, and key metrics abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5098.
Wentzensen et al. (Fri,) studied this question.