Despite high initial response rates to standard first-line therapies (surgery and platinum-based chemotherapy), the majority of patients with advanced high-grade epithelial ovarian cancer experience recurrence within three years. Traditional surveillance methods, including the CA-125 tumor marker and radiological imaging, often lack the sensitivity required to detect minimal residual disease (MRD) at a molecular level, limiting the window for early therapeutic intervention. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, non-invasive technology capable of reflecting tumor-specific genetic mutations and real-time molecular profiling.
This prospective, non-interventional cohort study aims to comprehensively evaluate the clinical utility of blood-based ctDNA as an independent biomarker for predicting recurrence in patients with FIGO stage III-IV epithelial ovarian cancer. The primary objective is to determine whether the presence of ctDNA (MRD positivity) measured immediately after the completion of standard first-line therapy correlates significantly with Relapse-Free Survival (RFS).
To establish a baseline mutational profile, tumor tissue obtained during initial biopsy or debulking surgery (primary or interval) will undergo Next-Generation Sequencing (NGS). Longitudinally, peripheral blood samples (20 mL) will be collected at predefined critical time points: at initial diagnosis (prior to treatment), post-surgery, within 2-4 weeks after the completion of first-line adjuvant or maintenance therapy (baseline for post-treatment MRD), and every 3 months during the follow-up period for up to 36 months or until disease recurrence.
Cell-free DNA (cfDNA) will be extracted from the collected plasma and analyzed using a highly sensitive, validated NGS-based multigene panel (AlphaLiquid® 100). The analysis will quantify major genetic variants (Variant Allele Frequency [VAF] ≥ 0.1%).
By tracking changes in ctDNA dynamics and comparing them with standard follow-up modalities, the study will investigate the lead time of ctDNA detection over radiological recurrence and compare its sensitivity and specificity against CA-125. Ultimately, this research seeks to provide robust scientific evidence to support the integration of ctDNA-based MRD monitoring into standard surveillance protocols, potentially enabling personalized tracking strategies and earlier clinical decision-making for high-risk ovarian cancer patients.
