Utilizing commercial health insurance claims data to identify the impact of cancer screening and estimate the added benefit of a multicancer liquid biopsy ordered during routine physical exams.
Authors: Hathaway Christine , Paetsch Peter , Li Yali , Wu Jincao , Asgarian Sam , Parker Alex , Welsh Alley , Deverka Patricia A. , Cohain Ariella 
Published: June 2021

e22516 Background: Cancer is the second leading cause of death in the United States. Survival varies by cancer type, but treatment of earlier stage cancer is consistently associated with improved survival relative to treatment of later stage cancers, highlighting that earlier detection is critical to improving patient outcomes. While most current cancer screening modalities require dedicated clinic visits, a multi-cancer liquid biopsy (i.e. a blood test) could enable screening for multiple cancers during routine physical exams. Methods: Five years of longitudinal data for 750,000 individuals from the Blue Health Intelligence national database were used to identify mammography utilization and breast cancer diagnoses. We identified incident cases and used univariate ordinal logistic regression to evaluate the association of breast cancer screening with earlier stage at diagnosis. We then identified all other incident cancers and characterized physical exam utilization in the two years prior to diagnosis. Results: Absence of claims for biennial screening mammograms as well as longer times from screening to diagnosis were associated with more advanced stage at breast cancer diagnosis. Women who were not screened (N = 400) had 155% increased odds of a later-stage (stage III or IV) breast cancer diagnosis when compared with women who were screened via mammography (N = 1,365) ( p < 0.001). Elapsed time from the most recent screening mammogram to breast cancer diagnosis was also significantly associated with cancer stage. Women with a longer time lapse ( > 4 months) between their most recent screening mammogram and diagnosis (N = 356) had 87% increased odds of a later-stage breast cancer diagnosis (p < 0.001). This is consistent with guidelines emphasizing the importance of screening to detect early-stage cancers. Among all incident breast cancer cases, 23% (N = 400) had no evidence of a screening mammogram in the two years before diagnosis. However, 49% (N = 196) of these women did have a routine physical examination during that same period. On this basis, we estimate that an additional 11% of breast cancer cases could have been screened for if a liquid biopsy test was utilized during those physical exams. Extending this analysis to include all incident cancer cases, 60% (N = 5,022) of the cohort had a routine physical exam in the two years prior to their cancer diagnosis. Conclusions: Our analyses confirm the association of cancer screening with earlier stage at diagnosis for breast cancer. Further, this research suggests opportunities to screen for and potentially intercept 60% of all incident cancer cases by incorporating a multi-cancer blood-based test into routine care. Given the importance of improving early cancer detection rates, additional clinical work extending the initial conclusions presented here is warranted.