Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition condition characterized by a high lifetime risk for a wide spectrum of malignancies associated with germline pathogenic/likely pathogenic (P/LP) variants in the TP53 tumor suppressor gene. Secondary malignant neoplasms are particularly common. Early cancer detection through surveillance enables early intervention and leads to improved clinical outcomes with reduced tumor-related mortality and treatment-related morbidity. Since the 2017 publication of LFS tumor surveillance guidelines from the inaugural AACR Childhood Cancer Predisposition Workshop, understanding the genotype:phenotype relationships in LFS have evolved, and adaptations of the guidelines have been implemented in institutions worldwide. The "Toronto Protocol" remains the current standard for life-long surveillance
however, as outlined in this Perspective, modifications should be considered as to the use of certain modalities to target organs in an age-dependent manner. The Working Group's recommendations have also been extended to include a more detailed outline for surveillance in the adult TP53 P/LP variant carrier population based on the recognition that early education of both practitioners and patients on what to expect after the transition from childhood/adolescence to young adulthood is important in preparing them for changes in surveillance strategies. In this perspective, we provide an up-to-date clinical overview of LFS, and present our updated consensus tumor surveillance recommendations from the 2023 AACR Childhood Cancer Predisposition Workshop.