Prognostic value of perioperative circulating tumor DNA in endometrial cancer: systematic review & meta-analysis.

[IMPORTANCE] Decisions regarding endometrial cancer (EC) adjuvant therapy can be challenging due to the need to balance the benefits of recurrence reduction with treatment toxicity. Circulating tumor DNA (ctDNA) has the potential to guide adjuvant therapy decisions by stratifying patients based on their risk of recurrence.

[OBJECTIVE] To determine the association between perioperative ctDNA positivity and survival outcomes in patients with EC.

[METHODS] An electronic search was performed in MEDLINE, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, and Web of Science and included all articles up to July 23rd, 2025. Studies were included if they assessed patients with EC who had ctDNA assessment before and/or after surgery and reported on survival outcomes. Meta-analysis was done to explore the association between ctDNA levels and survival.

[MAIN OUTCOME AND MEASURES] The primary outcome was the association between ctDNA positivity pre- or post-operatively and progression-free survival (PFS).

[RESULTS] Of 2862 articles reviewed, 11 met inclusion criteria, which led to reporting on 1298 patients. Pre-operative as well as post-operative ctDNA positivity was significantly associated with worse PFS (HR 3.69 [95 % confidence interval (CI), 2.58-5.26], HR 12.61 [95 % CI, 8.78-18.13] respectively), with no significant heterogeneity.

[CONCLUSIONS AND RELEVANCE] This systematic review and meta-analysis demonstrates that perioperative detection of ctDNA positivity is significantly associated with worse PFS and could serve as a valuable tool for EC prognostication and guidance for adjuvant therapy decision-making. Prospective studies that evaluate the role of ctDNA in EC are needed for this to be implemented in clinical practice.