ctDNA as an Objective Marker for Postoperative Residual Disease in Primary Advanced High-Grade Serous Ovarian Cancer

Background/Objectives: The surgeon’s subjective intraoperative evaluation is the standard of care to assess postoperative residual disease (RD) in advanced epithelial ovarian cancer (EOC). We investigated the feasibility of ctDNA as an objective marker for postoperative RD. Methods: This prospective study included 27 patients with advanced ovarian cancer (FIGO IIIA1–IVB) who underwent primary surgery between July 2021 and July 2022. Blood samples were analyzed preoperatively and on days 2 (d2) and 10 (d10) postoperatively. Low-coverage whole genome sequencing (WGS) was used to identify structural variants (SVs) at single-base pair resolution, single nucleotide variants (SNVs), and indels in tumor tissue to develop personalized, tumor-informed digital polymerase chain reaction (dPCR) fingerprint assays for each patient. Results: dPCR fingerprint assays were successfully developed for all patients by identifying one to eight SVs/SNVs per patient. ctDNA was detected in 96% (n = 26/27) of patients preoperatively and in 81% (n = 22/27) of patients at d10. Median ctDNA levels at d10 were significantly higher in patients with postoperative RD (median 367.38 copies (cps)/mL, 2.84% variant allele frequency; VAF) than in patients without postoperative RD (median 0.92 cps/mL, 0.017% VAF, p < 0.001). In patients with postoperative RD, ctDNA levels increased from the preoperative stage to d10 in seven out of eight patients (p = 0.016). In patients with complete tumor resection, ctDNA levels decreased from the preoperative stage to d10 in 17/19 patients (p < 0.001). Conclusions: A tumor-informed personalized ctDNA approach demonstrated feasibility, providing extremely high detection rates pre- and postoperatively. These results indicate that this approach could potentially be used for postoperative RD assessment in patients with primary advanced EOC.