BACKGROUND
Identification of children and infants with Li-Fraumeni syndrome (LFS) prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS).
METHODS
We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from SEER, ClinVar and gnomAD and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life years and costs associated with usual care and TP53-NBS.
RESULTS
Under usual care, out of 4 million newborns, 608 individuals (Uncertainty Interval [UI] = 581-636) would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% overall (UI = 4.0-12.1%) via early malignancy detection. Compared to usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106,009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100,000 per-life-year-gained willingness-to-pay threshold. Using this threshold, a value-of-information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million).
CONCLUSIONS
While we found that TP53-NBS could be cost-effective, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.