Early cancer detection in a large American Cancer Society cohort study: Retrospective analysis of methylated DNA biomarkers

BACKGROUND: Cancer biobank studies can inform the natural history of cancer and possibilities for earlier detection. The authors investigated the detectability of a cell-free DNA methylation-based cancer signal in biobanked plasma samples from the large American Cancer Society Cancer Prevention Study 3. METHODS: In total, 303,692 participants provided a blood sample at enrollment (2006-2013) and were followed for cancer incidence and mortality through state cancer registries. Samples were obtained from participants with and without a diagnosis of cancer (up to 3 years after enrollment), and their prediagnostic plasma samples were tested for cancer signals. RESULTS: For 1371 participants without cancer, zero cancer signals were detected. For 1383 participants who were diagnosed with cancer within a 3-year period, cancer signal detection depended on the time between blood draw and cancer diagnosis. Among all cancers, detectability was 15.2%, 6.0%, and 2.3% for samples collected 1, 2, and 3 year(s) before diagnosis, respectively. Among cancers that went on to be fatal, detectability was 55.1%, 21.6%, and 5.1%, respectively; among nonfatal cancers, detectability was 10.2%, 4.1%, and 1.8%, respectively. Cancer signal detection occurred, on average, 323 days before clinical diagnosis, with 40% of signal detections occurring greater than 1 year prior, including some cases up to 3 years prior. CONCLUSIONS: Cancer signal detection rates change rapidly as lead time approaches clinical diagnosis. The average lead time of approximately 1 year supports annual screening intervals.