Surveillance adherence and clinical findings in children with confirmed or familial TP53 variants: the Swedish multicenter constitutional TP53 study (SWEP53).

Abstract

Purpose: Li-Fraumeni Syndrome (LFS) is a cancer predisposition syndrome caused by germline TP53 variants. Guidelines recommend intensive surveillance from birth to enable early tumor detection. Pediatric adherence, germline testing behaviors, false-positive rates, and downstream work-up remain unstudied. Understanding these factors is essential to optimize surveillance and mitigate harm.

Methods: Pediatric SWEP53 (2016-2024) was a Swedish nationwide, prospective, multicenter surveillance study of individuals <18 years with a confirmed or 50% risk of a pathogenic or likely pathogenic germline TP53 variant (n = 37). Surveillance comprised quarterly clinical examination, abdominal ultrasound, and urine steroid profiling.

Results: Surveillance adherence ranged from 77% to 97% and was lowest for urine sampling due to limited time and motivation. Germline testing occurred frequently within the first year (p < 0.001). One of two cancers diagnosed during the study was through surveillance. The false-positive rate was 12% per person-year, primarily triggered by clinical examinations (60%) and abdominal ultrasounds (27%). Overall, 35% experienced at least one false positive (median time: 1.3 years), prompting imaging or specialist referral; one case required invasive diagnostics.

Conclusion: Pediatric LFS surveillance shows high adherence and early germline TP53 testing uptake, but notable false-positive rates. These results may guide clinical handling and surveillance guidelines.