Multicancer Detection Tests for Screening

Screening for multiple types of cancer with a single blood test is potentially transformative. To assess the benefits, accuracy, and harms of screening with blood-based multicancer detection (MCD) tests in asymptomatic adults. MEDLINE, Cochrane Library, trial registries, and relevant websites through March 2025. Controlled studies of MCD tests (for example, cell-free DNA) in asymptomatic populations reporting cancer detection, mortality, quality of life, and harms (psychosocial, adverse events, decrease in standard-of-care screening); uncontrolled studies for harms of diagnostic evaluation; test accuracy studies. One reviewer extracted data; a second checked for accuracy; 2 reviewers independently assessed risk of bias (ROB) and strength of evidence. No controlled studies evaluated benefits of screening. Twenty studies (n = 109 177) reported accuracy for 19 MCD tests. Seven studies (5 with high ROB, 2 of unclear ROB) reported the accuracy of future cancer detection in asymptomatic persons followed for 1 year (prediagnostic performance); the rest estimated accuracy from high ROB case-control studies in clinically confirmed cancer cases and healthy, cancer-free, control participants (diagnostic performance). Across tests, sensitivity ranged from 0.095 to 0.998, specificity ranged from 0.657 to 1.0, and area under the curve (AUC) ranged from 0.52 to 1.0. Sensitivity and AUC were higher in diagnostic performance compared with prediagnostic performance studies. No other patterns in accuracy were discernible. One cohort study reported harms; however, these data were limited. English-language studies only. Heterogeneity precluded quantitative synthesis of accuracy; estimates from the diagnostic performance studies may not be applicable to screening. No controlled studies are completed that report benefits of screening with MCD tests; evidence was judged insufficient to evaluate harms and accuracy. Accuracy varies by test and study design. Agency for Healthcare Research and Quality. (PROSPERO: CRD42024570793).