Health Economic Evidence and Modeling Challenges for Liquid Biopsy Assays in Cancer Management: A Systematic Literature Review

Background Cancer-derived material circulating in the bloodstream and other bodily fluids, referred to as liquid biopsies (LBs), has become an appealing adjunct or alternative to tissue biopsies, showing vital promise in several clinical applications. Purpose A systematic literature review was conducted to (1) summarize the current health economic evidence for LB assays and (2) identify and analyze the studies addressed or reported on the challenges of health economic modeling in precision medicine. Methods Relevant studies were identified in the EMBASE, MEDLINE, Cochrane Library, EconLit, and the University of Melbourne Full Text Journal databases from 1 January 2013 to 16 September 2022. Included papers were selected if they were economic evaluations and/or budget impact analyses. Results A total of 24 studies were included and analyzed, with the majority being full economic evaluations (n = 19, 79.2%). Four studies (16.7%) were health and budget impact analyses, and one study (4.1%) incorporated both an economic evaluation and a budget impact analysis. Cohort-level modeling techniques were the most common approach (n = 16; 80%). LB technologies were cost-effective in 15 studies (75%) considering different biomarkers, cancer types and stages, and economic analyses. These studies evaluated LBs for screening and early detection (66.7%), treatment selection (26.7%), and monitoring treatment response (6.6%). Budget impact analysis results were varied among included studies, with the majority of studies (n = 4; 80%) reporting either cost savings, minimal, or modest budget impact, while one study (20%) reported LBs as an efficient strategy. The reviewed studies often inadequately reported or addressed modeling challenges, such as patient-level processes, the combination of tests and treatments, preferences, and uncertainty. Conclusion LBs could provide a cost-effective approach for treatment selection in lung cancer and aid in the screening and early detection of other cancers, including colorectal, gastric, breast, and brain cancers. This is in comparison with various alternatives, such as the standard of care (SOC) and no screening scenario. However, it is important to mention that in some comparisons, LBs were used in combination with SOC instead of replacing it. Importantly, few studies have pointed toward LBs’ cost-effectiveness for monitoring treatment response. Most health and budget impact analyses, especially those focused on lung cancer, suggest potential cost savings or a minimal-to-moderate budget impact. Nevertheless, additional research is needed to ascertain their effectiveness across various stages of lung and colorectal cancer, as well as to address potential modeling challenges. Systematic review registration PROSPERO CRD42022307939.