Prospective study of a multi-modal blood-based test for colorectal cancer screening.
Authors: Paloma Peinado, Enrique Sanz-Garcia, Clara O. Montagut, Maria Teresa Curiel, Susana Prados, Rafael Álvarez, Cesar Gregorio Muñoz, Lisardo Ugidos, Enrique de la Fuente, Ana Bargalló García, Carmen Toledano, Luka Mihic, Theresa Hoang, Victoria M. Raymond, Antonio Cubillo Gracian
Journal: Journal of Clinical Oncology (2024)

70 Background: Colorectal cancer (CRC) screening has proven to be a useful tool for the detection and prevention of CRC. However, adherence is low despite the multiple screening options available. A blood-based CRC screening test with optimized sensitivity and specificity may improve screening adherence. We aimed to prospectively evaluate the performance of a multimodal blood-based colorectal neoplasia screening test in individuals presenting for colonoscopy. Methods: This prospective, observational study was developed in four hospitals in Spain and enrolled individuals (45 – 84 years of age) undergoing colonoscopy, including diagnostic and screening colonoscopies, between March 2020 and September 2021. Eligible individuals consented to use of medical records for research and to provide a blood sample prior to colonoscopy procedure. Individuals were followed for one year. Whole blood was collected and shipped ambient to a central laboratory for analysis (Shield, Guardant Health, Redwood City, CA, USA). The blood-based colorectal neoplasia test is a 500kb next-generation sequencing based panel and bioinformatic platform that incorporates cell-free DNA (cfDNA) methylation-based partitioning to identify cancer related genomic alterations and epigenomic modifications (methylation and modifications in chromatin state). Results are integrated to yield a binary “positive” or “negative” result. Here we present findings correlating the blood-based test results with colonoscopy findings and findings from available 1-year follow-up data. Results: 556 out of 598 eligible individuals had an evaluable colonoscopy and a blood-based test result that passed quality control standards. Of the 556 individuals, 52% were female; median age was 55 years (21% age 45 – 49, 74% age 50 – 74, 4% age 75+). Reasons for colonoscopy were symptoms (49%), average risk screening (33%), positive stool-based test (6%), positive family history (11%) or other reasons (1%). Colorectal adenocarcinoma prevalence rate was 1.4%. Sensitivity for CRC detection was 100% (8/8; Stage I, 1; Stage II, 3; Stage III, 2; Stage IV, 2). Sensitivity for advanced adenoma (AA) detection was 22%. Specificity for advanced neoplasia (CRC + AA) was 91%. Negative predictive value (NPV) for CRC detection was 100% and positive predictive value (PPV) was 13%. 1-year follow-up data was available for 504 individuals, of whom 9 patients developed cancer (none CRC), of whom 1 had an initial positive Shield result. Conclusions: In this prospective study of individuals eligible for colonoscopy, sensitivity and specificity of the blood-based test showed a performance consistent with the available stool-based non-invasive screening options. This, combined with a more acceptable mode of testing suggests that this blood-based test may be a viable CRC screening option.