Introduction Adjuvant therapy is often used in high risk endometrial cancer (HREC) due to increased risk of recurrence. Histology alone does not accurately predict recurrence. Circulating tumor DNA (ctDNA) is a validated prognostic biomarker for many solid tumors, yet its utility in HREC is unclear.

Methods In an ongoing, prospective registry, serial plasma samples were collected pre- and post-hysterectomy, and post-adjuvant treatment (AT) from 25 patients with newly diagnosed HREC treated with primary surgery. CtDNA was detected using a tumor-informed assay (Signatera^TM Natera, Inc.) and correlated with recurrence-free survival (RFS).

Results Personalized ctDNA assays were successfully designed for 24/25 patients. Median age was 63 years (range: 30–74). Pre-operatively, ctDNA was detectable in 60.87% patients (median 1.3 mean tumor molecules/mL), with 55% and 80% in stage I and II-IV, respectively. ctDNA cleared with surgery in 83% (10/12) patients; only one (10%) of these patients recurred. Three patients were ctDNA-positive post-operatively; 2/3 remained ctDNA-positive post-AT and recurred; 1/3 cleared ctDNA post-AT and remained disease-free. Seven patients recurred; ctDNA-positivity was observed in 43% (3/7) pre-operatively, 33% (2/6) post-operatively, and 29% (2/7) post-AT. There was no association between pre-operative ctDNA and recurrence (p=0.27). Post-AT, ctDNA-positivity was significantly associated with shorter RFS compared to ctDNA-negativity (p=0.02; HR=7.92; 95%CI: 1.43–43.73).

Conclusion/Implications Post-AT ctDNA negativity and/or clearance were associated with better response and RFS in HREC patients. ctDNA detection was feasible across multiple timepoints in early-stage HREC patients. Future studies will determine whether the addition of ctDNA to other molecular/histologic characteristics can identify patients who may benefit from escalation/de-escalation of AT.