Introduction Multicancer early detection (MCED) tests aim to detect multiple types of cancer in their early asymptomatic stages when treatment outcomes are more favourable. Concerns have been raised regarding how these tests could be integrated into standard care and existing diagnostic pathways particularly regarding false positive results. This systematic review (PROSPERO registration: CRD420251060729) investigates the false positive rate (FPR) of MCED technologies when applied to the asymptomatic general population and the extent of diagnostic follow-up. Secondary outcomes included the impact of these tests on patients and healthcare systems. Research design and methods The databases Embase, Medline, Scopus and Eric were searched in June 2025, as well as the trial registers WHO and ClinicalTrials.gov. All case-control, cohort studies and randomised controlled trials which recruited an asymptomatic population and reported accuracy measures were included. For the risk of bias assessment, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 scale was used. Results The search identified 7509 publications with 34 papers included for analysis after screening. They recruited 83 637 participants in total. Overall, 97.1% of included papers reported FPRs from the use of MCEDs, with an average of 4.0 (median 2.2, IQR 3) for case-control and 3.3 (median 3.8, IQR 3.3) for cohort studies. Only two studies reported data on the types and numbers of additional investigations, and many studies had minimal focus on patient experience. Most studies performed poorly on the risk of bias assessment, and relevant conflicts of interest (COI) were identified in 80% of studies which included a COI statement. Conclusions While FPRs were low in controlled environments, this systematic review is limited by the lack of evidence on the performance of MCED tools in real-world cohorts. Data on patient follow-up were largely absent, and as such, there is a pressing need for trials that are independent, randomised and interventional to establish standardised pathways for the investigation of positive results from MCEDs. These trials should aim to minimise both mental and physical harm to patients and costs to health services. Significant progress must be made in these areas before MCED screening in the general population becomes feasible.
Romeikat et al. (Mon,) studied this question.