Circulating tumor DNA to enhance detection of high-risk minimal residual disease in ovarian cancer relative to second look laparoscopy.

5567 Background: Minimal residual disease (MRD) following frontline treatment of ovarian cancer has been established as a predictor of recurrence and survival. Historically, second look laparoscopy (SLL) has served as the gold-standard method to assess MRD; however the need for surgical evaluation limits widespread adoption and clinical applicability. Circulating tumor DNA (ctDNA) offers a non-invasive alternative for MRD detection and enables longitudinal monitoring with the potential for early identification of recurrence. Presently, the concordance between ctDNA-based detection and surgical assessment remains incompletely characterized. In this retrospective cohort study, we compare the predictive performance of ctDNA versus SLL for detecting clinically significant MRD after frontline treatment for high-grade ovarian cancer. Methods: This retrospective, single-institution study included patients with high-grade epithelial ovarian cancer who completed frontline chemotherapy and surgery. All patients underwent SLL to determine surgical MRD status. At the time of SLL, plasma was collected and profiled using NeXT Personal. Using whole-genome sequencing, this ultrasensitive, tumor-informed assay tracks up to 1,800 tumor-specific variants to detect ctDNA at levels down to ~1 part per million. Statistical analyses were conducted using RStudio (version 2026.01.0.392). Results: The cohort consisted of 72 patients (median follow up 38.9 months) with high-grade epithelial ovarian cancer, of whom 69 patients (95.8%) were in clinical remission by Ca-125 and imaging. Despite this, 30 patients (41.7%) were positive for MRD by ctDNA and 33 patients (45.8%) were positive for MRD by SLL. On multivariable analysis, ctDNA positivity independently predicted worse PFS (HR 4.35, 95% CI 2.17-8.72, p