Using Circulating Tumor DNA-Based Molecular Residual Disease Detection for Postoperative Monitoring in Early-Stage Uterine Cancer.

Clinical decision making for adjuvant treatment in early-stage uterine cancer (UC) following surgery is typically directed by clinicopathological risk factors. There is an unmet need for a clinically relevant biomarker to improve individualized risk stratification and help monitor response to adjuvant therapy. Here, we sought to analyze circulating tumor DNA (ctDNA) as a prognostic biomarker in patients with early-stage UC. Retrospective analysis of ctDNA results from real-world data was performed for 61 patients (233 plasma time points) diagnosed with early-stage UC. ctDNA status and dynamics were assessed using a clinically validated, personalized, tumor-informed ctDNA assay (Signatera), and its association with recurrence-free survival (RFS) was evaluated. ctDNA positivity was associated with significantly reduced RFS postoperatively (hazard ratio HR, 7.6; P = .003) and postdefinitive therapy (HR, 25.4; P = .0009) and was the most significant factor associated with recurrence when compared with other clinicopathological and molecular risk factors. Notably, of patients who recurred and for whom clinical outcomes were available, 100% were ctDNA-positive before or at the time of recurrence, whereas none of the serially ctDNA-negative patients experienced relapse. Our data demonstrate the feasibility of monitoring ctDNA in the postoperative and adjuvant settings in early-stage UC. Analysis of ctDNA, in addition to other risk factors, may help identify patients at the highest risk of recurrence, inform surveillance strategies, and support treatment decision-making for these patients.