There is a critical need for accessible biomarkers to improve prognostic assessment and guide clinical management.<h4>Methods</h4>In this study, we evaluated the feasibility and clinical relevance of monitoring circulating tumor DNA (ctDNA) by tracking somatic <i>TP53</i> mutations using a routine next-generation sequencing (NGS) assay already implemented in diagnostic practice.<h4>Results</h4>Among 21 patients with high-grade EC carrying <i>TP53</i> mutations in the primary tumor, ctDNA was detectable in over 75% during follow-up. Here, TP53 is linked to neoplasm.