Prognostic value of perioperative circulating tumor DNA (ctDNA) in endometrial cancer with high-risk features: a prospective observational study

Introduction: Although circulating tumor DNA (ctDNA) has emerged as a promising prognostic tool in various malignancies, evidence in endometrial cancer at high risk of recurrence is limited. This study evaluated the association of pre-and post-surgical ctDNA with advanced-stage disease, disease-free and overall survival in endometrial cancer with high-risk features. Material and methods: This prospective observational study was conducted at Mayo Clinic (7/2016-6/2021). Patients with endometrial cancer at preoperative biopsy, confirmed by final pathology, were included. Blood samples were collected before and 10 weeks after surgery. Tumor-specific junctions identified in pathology specimens and blood samples were used to detect ctDNA. Associations between pre-and post-surgical ctDNA and advanced-stage disease, recurrence, and death were evaluated using logistic regression [odds ratio (OR) and 95 % confidence interval] and Cox proportional hazards [hazard ratio (HR) and 95 % confidence interval]. Results: Thirty-six patients were included: 6 (16.7 %) intermediate risk, 1 (2.8 %) high-intermediate risk, 28 (77.8 %) high risk, and 1 (2.8 %) advanced metastatic. Detection of pre-or post-surgical ctDNA was not significantly associated with advanced disease (pre-surgical OR 5.69 [0.88-66.02]; post-surgical OR 5.86 [0.83-72.68]). Pre-surgical ctDNA did not significantly predict recurrence (HR 0.99 [0.30-3.23]) or death (HR 3.23 [0.40-25.91]). In contrast, post-surgical ctDNA was associated with increased risk of recurrence (HR 3.32 [1.05-10.51]) and death (HR 5.97 [1.11-36.08]). Conclusion: Post-surgical ctDNA detection was associated with poor outcomes in patients with endometrial cancer. These findings support the potential of ctDNA as a biomarker to personalize surveillance and guide post-surgical treatment strategies.