Abstract
BACKGROUND: Cancer detection remains a significant global healthcare challenge, and circulating tumor DNA (ctDNA) is a biomarker for noninvasive cancer screening. OBJECTIVE: This systematic review aimed to describe health economic evaluations of ctDNA for cancer screening. METHODS: A comprehensive literature search was performed (following PRISMA guidelines) across MEDLINE, Embase, APA PsycINFO, Cochrane Library, Web of Science, and the Center for Review and Dissemination. The review included full-scale health economic analyses such as cost-effectiveness, cost-utility, cost-benefit, and cost-consequence analyses. The quality of the included reports was assessed using CHEERS 2022 standards, and each report was categorized as excellent, very good, good, or insufficient. RESULTS: Eighteen studies were selected, including four ctDNA tests (EBV-DNA, cf-DNA, mSEPT9, and mt-sDNA) for three types of cancer screening: nasopharyngeal carcinoma (NPC) (2; 11.11%), breast cancer (BC) (1; 5.56%), and colorectal cancer (CRC) (15; 83.33%). Five studies (27.78%) found ctDNA cost-effective for CRC screening (mt-sDNA (with higher uptake than conventional tests) versus fecal immunochemical testing (FIT) or colonoscopy (n = 4); mSEPT9 versus computed tomography colonoscopy (CTC) (n = 1)). Thirteen studies (72.22%) found ctDNA not cost-effective for NPC (EBV-DNA versus no screening (n = 2)); BC (cf-DNA versus conventional testing (n = 1)); CRC (mSEPT9 versus FIT or colonoscopy (n = 2)); mt-sDNA versus FIT or colonoscopy (n = 5); mSEPT9 or mt-sDNA versus conventional tests (n = 3)). The CHEERS assessment found all reports in the "very good" category. CONCLUSION: All ctDNA tests were generally not cost-effective comparing to conventional screening methods, except when the mt-sDNA uptake was higher than the comparators or when mSEPT9 was compared with CTC. TRIAL REGISTRATION: CRD42023477732.