Clinical significance of circulating tumor DNA monitoring based on TP53 mutation in high-grade serous ovarian cancer patients

Background: High-grade serous ovarian cancer (HGSOC) is characterized by aggressive clinical behavior and a high risk of recurrence. Cancer antigen 125 (CA-125) is widely used for monitoring treatment response and disease recurrence; however, its limited sensitivity and specificity, particularly during surveillance, highlight the need for more reliable biomarkers. Circulating tumor DNA (ctDNA) has emerged as a promising tool for real-time disease monitoring, and TP53 mutations-present in nearly all HGSOC cases-provide an ideal target for personalized ctDNA-based assays. This study evaluated the translational utility of patient-specific TP53 mutation-based ctDNA monitoring using droplet digital PCR (ddPCR) in patients with HGSOC. Methods: We conducted a prospective, observational, single-institution study of 25 patients diagnosed with HGSOC. All patients underwent primary debulking surgery followed by adjuvant chemotherapy. Tumor tissues were analyzed to identify patient-specific TP53 mutations, and corresponding plasma samples were analyzed using ddPCR. TP53 mutant allele count (TP53MAC) levels were measured longitudinally throughout the treatment period and follow-up and were compared with CA-125 levels. Results: All TP53 mutations identified in tumor tissues were concordantly detected in matched plasma ctDNA samples, confirming the analytical validity of ddPCR-based TP53MAC assessment. TP53MAC levels declined significantly after surgery (P=0.003) and chemotherapy (P=0.01), in parallel with reductions in CA-125. Longitudinal monitoring demonstrated heterogeneous biomarker dynamics, with discordant patterns between TP53MAC and CA-125 observed in selected recurrent cases. In receiver operating characteristic curve analyses, TP53MAC showed predictive performance comparable to CA-125 across treatment and follow-up time points. At a fixed specificity of 78-80%, TP53MAC demonstrated higher sensitivity and positive likelihood ratios than CA-125 at selected post-treatment time points. Conclusions: TP53 mutation-informed ctDNA monitoring using droplet digital PCR may provide complementary clinical information as an adjunct to CA-125 for assessing treatment response and detecting disease recurrence in patients with HGSOC, supporting its potential role in longitudinal disease surveillance.