ABSTRACT Late‐stage cancer diagnosis and limited treatment options for advanced disease remain major contributors to cancer‐related morbidity and mortality. Blood‐based multicancer early detection (MCED) assays have consequently gained momentum as a means to shift diagnosis toward earlier, more curable stages. Despite their promise, substantial methodological, clinical, and implementation barriers hinder widespread adoption. Integrative approaches coupling multi‐omics profiling with advanced molecular imaging may improve detection accuracy and tumor localization, while risk‐adapted MCED paradigms could support more targeted, individualized screening strategies. This article reviews the current landscape of MCED technologies, with a primary focus on circulating cell‐free DNA and circulating tumor DNA–based assays, and critically evaluates their developmental status, strengths, and limitations relative to established single‐cancer screening methods. The contribution of artificial intelligence, particularly advanced deep learning, to improving sensitivity, specificity, and predictive performance is discussed. The potential of MCED assays to detect aggressive, currently unscreened malignancies and to address the unique challenges of pediatric cancers is examined. In addition, emerging alternative detection strategies, ongoing clinical validation efforts, regulatory requirements, and implementation considerations are reviewed. Finally, the impact of MCED testing on cancer mortality, quality of life, and healthcare systems is outlined, along with key technological trends shaping future development and clinical translation.
Emma Di Carlo (Sun,) studied this question.