Abstract 3331: Highly sensitive blood-based multi-cancer screening device with tiered specificity based on diagnostic workflow

Abstract Background. Multi-cancer blood-based tests may yield clinical benefit by improving compliance to guideline recommended screening with a more patient-friendly modality, and also by detection of early (stage I/II) tumors in cancer types that lack screening tests, yet early intervention can save lives. A single test with clinically meaningful performance which addresses both opportunities has yet to be developed. Methods. We evaluated a blood-based multi-modal device based on cfDNA epigenomic and targeted protein analysis that enables high performance for early-stage cancer detection in colon, lung, bladder, gastric, liver, ovarian, and pancreas cancers. Blood samples were obtained from multiple case-control cohorts of individuals with colorectal (N > 2,000), lung (N > 300), and other solid tumor cancers (bladder, gastric, liver, ovarian, pancreas (N > 300)) as well as individuals without cancer (N > 3,000). The assay is based on Guardant Shield™ blood-based CRC screening test and the bioinformatic pipeline is augmented with a multi-cancer screening caller for the detection of additional cancers. Sensitivity for CRC and lung cancer detection is calculated at 90% target specificity thresholds, due to availability of guideline recommended screening tests, colonoscopy and LDCT scan to adjudicate blood-based test results. Specificity for all other cancers were targeted at an overall specificity of 98%. The specificity thresholds for CRC, lung, and multi-cancer are selected to yield assay performance tailored for the cancer type and clinical diagnostic pathway. Results. In this study cohort, this integrated, single device, multi-cancer test yielded CRC sensitivity of 91% (stage I/II: 93%) and lung cancer sensitivity of 85% (stage I/II: 75%) at 90% specificity. The overall sensitivity in bladder, gastric, liver, ovarian, and pancreas cancers was 75% (stage I/II: 66%) at 98% overall specificity. Overall prevalence-adjusted sensitivity of this device in the above 7 cancers were 79% overall sensitivity (stage I/II: 78%). This blood-based test could detect 25% of the expected cancer diagnoses in 2022 according to SEER estimates. Conclusions. This highly-sensitive, integrated, blood-based cancer screening device yields performance on par with currently available screening tests for cancers with screening guidelines (CRC and lung) and clinically meaningful early-stage detection in cancer types without screening guidelines where early intervention can bring clinical benefit, highlighting the ability of this technology to yield clinically meaningful results for the detection of early stage cancer. The performance of this device is under investigation in prospective screening trials. Citation Format: Yupeng He, Anton Valouev, Liyang Xiong, William W. Young Greenwald, Victoria M. Raymond, Sven Duenwald, AmirAli Talasaz. Highly sensitive blood-based multi-cancer screening device with tiered specificity based on diagnostic workflow [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3331.