Key Clinical Summary:

• Design/Population: A prospective cohort study evaluated longitudinal ctDNA monitoring in newly diagnosed patients with advanced stage high-grade serous ovarian cancer undergoing neoadjuvant chemotherapy, interval debulking surgery, and adjuvant chemotherapy. 
• Key Outcomes: ctDNA clearance was associated with improved outcomes, with no recurrences observed among patients with sustained clearance. Persistent ctDNA positivity was associated with early recurrence and platinum-resistant disease.
• Clinical Relevance: ctDNA dynamics may serve as a real-time, minimally invasive biomarker for treatment response and recurrence risk in advanced ovarian cancer, with potential to guide risk stratification and prediction of platinum sensitivity, warranting validation in larger prospective trials.

Results from a prospective cohort study demonstrate that longitudinal circulating tumor DNA (ctDNA) monitoring can potentially serve as a strong, real-time biomarker for response and recurrence among patients with advanced, high-grade serous ovarian cancer.  

These findings were presented by Emily O'Brien, MD, University of Alabama, Birmingham, Alabama, at the 2026 Society of Gynecologic Oncology (SGO) Annual Meeting in San Juan, Puerto Rico.

In this study, researchers collected tissue and plasma samples from 15 newly diagnosed patients with stage III or IV disease who underwent neoadjuvant chemotherapy, interval debulking surgery, and adjuvant chemotherapy. Longitudinal blood samples were collected at baseline (pre-neoadjuvant chemotherapy), post-neoadjuvant chemotherapy and pre-surgery, post-surgery, and post-adjuvant chemotherapy. Signatera Genome™ ctDNA assays were built using whole-genome sequencing data of matched tumor and normal blood samples. These assays were used to detect and quantify plasma ctDNA in mean tumor molecules (MTM) per mL. 

At a median follow-up of 13.1 months, 45% of patients experienced disease recurrence. ctDNA was detectable in all patients at baseline, with detection rates of 71% post-neoadjuvant chemotherapy, 60% post-surgery, and 53% post-adjuvant chemotherapy. Among patients who were ctDNA positive at each timepoint, the median MTM/mL were 165, 0.6, 1.1, and 20.7, respectively. 

By the end of treatment, 7 patients achieved persistent ctDNA clearance, of which 4 occurred post-neoadjuvant chemotherapy and pre-surgery and 3 occurred either post-surgery or post-adjuvant chemotherapy. At a median follow-up of 15.4 months from the end of adjuvant chemotherapy, none of the patients who achieved persistent ctDNA clearance during therapy experienced recurrence. At a median follow-up of 17.8 months from adjuvant chemotherapy, 10 patients remained disease-free, and the median MTM/mL was 81. 

Among patients who did not clear their ctDNA, 5 patients experienced disease recurrence. The recurrence-free survival interval was 3.5 months from the end of adjuvant chemotherapy, and the median MTM/mL was 287.8. Clinical follow-up is ongoing for the 3 remaining patients who did not clear their ctDNA and did not experience disease recurrence. Eighty percent of patients who experienced disease recurrence were persistently ctDNA positive across all timepoints and were platinum-resistant or refractory at the time of recurrence. The 1 platinum-sensitive recurrence had transient ctDNA clearance before converting back to ctDNA positive at recurrence. 

“ctDNA dynamics provided early and refined risk stratification, supporting its role as a real-time biomarker of treatment response and recurrence risk,” concluded Dr O’Brien. “Future prospective trials could further inform the role of ctDNA clearance as a predictive biomarker of platinum sensitivity/survival.”

Source:

O’Brien E, Edwards C, Scalise SC, et al. Clinical performance of signatera genome assay to predict treatment response in patients with advanced-stage ovarian cancer receiving neoadjuvant chemotherapy. Presented at SGO Annual Meeting on Women’s Cancer. April 10 - 13, 2026; San Juan, Puerto Rico. LBA4.