Phase 3 Signatera ctDNA MRD assay (tumor-informed personalized ctDNA tracking) vs vaginal brachytherapy in early endometrial cancer.

This Phase 3, randomized, multicenter study tests whether a ctDNA-guided “de-escalation” strategy after surgery is safe in Stage I high-intermediate risk endometrial cancer. Natera sponsors the trial using its Signatera Genome assay, a tumor-informed minimal residual disease (MRD) approach that designs a personalized ctDNA panel from a patient’s tumor (targeting patient-specific variants) and then serially tracks those variants in plasma to detect molecular residual disease. Participants who are ctDNA-negative in the specified post-op baseline window are randomized 1:1 to observation with serial ctDNA monitoring versus standard adjuvant vaginal brachytherapy (VBT), with 3-year recurrence-free survival assessed for non-inferiority of ctDNA-guided observation. The commercial/scientific angle is using MRD negativity to spare radiation in patients likely already cured by surgery while still surveilling closely for molecular relapse. Today, many Stage I high-intermediate risk patients receive adjuvant VBT to reduce vaginal cuff recurrence risk, while some are observed based on clinicopathologic factors; this trial asks whether ctDNA can more precisely select who can safely skip VBT.