Circulating Tumor DNA (ctDNA) as a marker of residual disease and recurrence risk in resected stage I IV epithelial ovarian cancer (EOC).

Abstract

Patients with epithelial ovarian cancer (EOC) often relapse despite surgery and chemotherapy. Current prognosis estimates, based on FIGO staging molecular features lack precision. Standard of care for stage I III EOC is 6 cycles of adjuvant chemotherapy, which may include 3 cycles of neoadjuvant treatment. Many treated patients do not benefit from chemotherapy because they had no residual disease post operatively or because treatment did not eradicate disease that was present. Studies in multiple solid tumor types have demonstrated that after curative intent surgery detectable ctDNA a marker of minimal residual disease (MRD) predicts a very high risk of recurrence. Our primary aim was to explore the association between detectable ctDNA following debulking of primary EOC and recurrence free survival (RFS). Secondary aims included exploring the relationship between ctDNA and RFS at EOC diagnosis, following neoadjuvant therapy and post adjuvant chemotherapy. In a prospective cohort of patients with epithelial ovarian cancer analysed for ctDNA Neoadjuvant therapy cohort - ctDNA was detectable pre treatment in most patients. Most pre treatment ctDNA ve patients remained ctDNA ve despite chemotherapy. Post cancer cytoreduction surgery cohort - ctDNA was more likely to be detected in patients with stage III/IV disease, those with residual disease, and those without a BRCA mutation. ctDNA detection was associated with 2 year RFS. Post adjuvant chemotherapy cohort - ctDNA detection was associated with a trend to inferior 2 year RFS.