Liquid biopsy-based multi-cancer early detection: an exploration road from evidence to implementation.

Abstract

Current cancer screening methods are limited in scope, often detecting only a few cancer types with low positive predictive value and suboptimal patient adherence. In recent years, liquid biopsy-based multi-cancer early detection (MCED) has emerged as a promising approach to revolutionize cancer control. Despite several MCED tests reaching clinical trial phases and seeking regulatory approval, none have yet been approved for clinical use, highlighting uncertainties regarding their efficacy and applicability. This review comprehensively examines the advancements in MCED technologies and offers insights into the selection of cancer types for inclusion in MCED panels. We explore the clinical development pathway for MCED, from biomarker discovery and analytical validation to large-scale randomized controlled trials, emphasizing the importance of selecting appropriate endpoints such as reducing late-stage cancer incidence or cancer-specific mortality. Key challenges, including achieving optimal sensitivity for early-stage cancers, minimizing false positives and negatives, and ensuring equitable access to MCED tests, are also addressed. Finally, we evaluate the added value and health economic benefits of integrating MCED into established healthcare systems through widespread implementation. By providing a thorough analysis of these aspects, this review aims to advance the field of cancer screening and guide future research and development efforts.