Abstract
BACKGROUND: Next-generation sequencing (NGS) of plasma circulating tumor DNA (ctDNA) shows promise as a minimally invasive alternative to tissue sequencing. However, concordance between genomic alterations in tumor tissue and plasma ctDNA remains incompletely characterized in ovarian cancer, particularly in the pretreatment setting. OBJECTIVES: To identify factors influencing concordance between tissue and ctDNA genomic profiling and explore the potential clinical implications (including treatment and survival outcomes) of this concordance. DESIGN: A prospective, single-center, observational study. METHODS: A total of 40 matched pretreatment tumor specimens and blood samples were prospectively collected from patients with ovarian cancer and subsequently sequenced using a customized gene panel. Overall and individual concordance rates were calculated as the ratio of total concordant mutations to total tissue mutations, with patients stratified into highly concordant (⩾50%) and poorly concordant (<50%) groups. RESULTS: The overall tissue-plasma concordance rate was 40.8%, with shared variants exhibiting identical abundance patterns across sample types and capturing the majority of functionally relevant mutations. Single-nucleotide variants in tissue showed a higher detection rate in plasma than structural variants. Individual concordance rates displayed significant inter-patient variability. Higher tissue tumor mutation burden (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.183-3.965) and plasma ctDNA fraction (OR 1.433, 95% CI 1.063-1.933) were independently associated with high concordance rates. In advanced-stage patients, the poorly concordant group showed lower CA125 elimination rate constant K (KELIM) scores (median 0.7 vs 1.3; 15.0% vs 68.8% patients with score ⩾1), indicating reduced chemosensitivity. The poorly concordant group demonstrated a higher disease recurrence rate (40.0% vs 6.2%) and elevated early recurrence risk (12-month progression-free survival rate 82.0% vs 100.0%) compared with the highly concordant group. CONCLUSION: In the field of ovarian cancer, NGS of ctDNA showed moderate concordance with tissue-based sequencing in the pretreatment setting, influenced by both technical and biological factors. The tissue-plasma concordance may serve as a chemosensitivity and prognostic indicator.