5562 Background: Ovarian cancer has a high risk of recurrence, particularly in patients with advanced-stage disease. CA-125 is routinely used to assess disease burden and recurrence risk but has limited prognostic accuracy. Circulating tumor DNA (ctDNA) has emerged as a potential biomarker that may better reflect tumor biology and enable earlier identification of recurrence. Methods: Patients with epithelial ovarian cancer and available plasma ctDNA and CA-125 measurements collected in association with surgical debulking were included. CA-125 was stratified using a standard clinical cutoff of 35 U/mL. Average cfDNA yield (ng/mL) was stratified into high and low ctDNA groups based on the cohort median. Associations were assessed using correlation and categorical analyses. Overall survival (OS) was evaluated using Kaplan–Meier methods and Cox proportional hazards models, including multivariable analyses. Results: Among 89 patients, ctDNA concentration was positively associated with CA-125 (Spearman ρ = 0.25; p = 0.017). Patients with high CA-125 had higher ctDNA levels than those with low CA-125 (mean 21.2 vs 7.6; p = 0.0044). High ctDNA concentration was associated with worse OS compared with low ctDNA (log-rank p = 0.0036; HR 3.48, 95% CI 1.50–8.06), with median OS (mOS) of 1386 days versus not reached. Patients with both high CA-125 and high ctDNA experienced markedly worse mOS than patients with low ctDNA (log-rank p = 0.0045; HR 3.48, 95% CI 1.47–8.21), with a mOS of 827 days versus not reached respectively. This added stratification by ctDNA persisted across multiple sensitivity analyses, including stratification by timing of sample collection relative to surgery, with consistent prognostic associations observed in pre-surgery samples (mOS 953 days; log-rank p = 0.031) and post-surgery samples (mOS 569 days; log-rank p = 0.045), as well as in analyses of high-grade serous ovarian cancer, advanced-stage disease, and neoadjuvant therapy. In multivariable Cox regression adjusting for CA-125, disease stage, surgical status, and neoadjuvant therapy, ctDNA remained independently associated with OS (HR 1.012, 95% CI 1.003–1.019). Conclusions: ctDNA consistently added prognostic value beyond CA-125 despite treatment-related heterogeneity, suggesting that ctDNA concentration captures biologic features of tumor behavior not reflected by CA-125 alone. Importantly, ctDNA remained predictive regardless of the timing of sample collection. These findings support ctDNA as a complementary biomarker for baseline prognostic stratification.
Gorecki et al. (Wed,) studied this question.