A Clearer Signal in Ovarian Cancer
Data suggest longitudinal ctDNA tracking may sharpen response assessment and recurrence risk prediction.
A simple blood test may offer a clearer, earlier read on how patients with advanced ovarian cancer are responding to treatment, potentially reshaping how clinicians monitor disease and anticipate recurrence.
Longitudinal circulating tumor DNA (ctDNA) is a potential real-time biomarker for treatment response and recurrence risk in advanced-stage ovarian cancer, offering a more dynamic view than current surveillance tools.
Presenting findings during her late-breaking abstract presentation earlier today, Emily O'Brien, MD, reported on the clinical performance of a ctDNA whole genome assay in patients with Stage III and IV ovarian cancer undergoing neoadjuvant chemotherapy (NACT), interval debulking surgery (IDS), and adjuvant chemotherapy (ACT).
“We were hoping to answer two main questions: first, whether ctDNA could serve as a predictive biomarker of response to neoadjuvant and adjuvant chemotherapy and, second, whether it could be used to help be predictive of recurrence over time,” said Dr. O’Brien, who is a gynecologic oncology fellow at The University of Alabama at Birmingham (UAB). “ctDNA is particularly important in this setting because it is a noninvasive biomarker that can provide real-time insight into tumor burden and treatment response. Compared with traditional markers like CA-125, ctDNA may offer greater specificity and a more direct measure of residual disease.”
The study followed 15 patients with advanced-stage, high-grade serous ovarian cancer treated between 2022 and 2024. Longitudinal blood samples were collected at four key time points — baseline, post-NACT, post-interval debulking surgery, and post-adjuvant therapy — and analyzed using tumor-informed ctDNA assays.
Detection rates declined over the course of treatment, from 100% at baseline to 53% after completion of therapy, reflecting a decrease in tumor burden. But it was the pattern of ctDNA change over time that proved most clinically meaningful.
“The longitudinal changes in ctDNA revealed that patients with persistent ctDNA positivity throughout treatment were more likely to have platinum-resistant disease and experienced a shorter time to recurrence,” Dr. O’Brien said. “In contrast, patients who cleared ctDNA during treatment appeared to have better, more durable responses and improved survival. Overall, these serial ctDNA measurements suggest that ctDNA dynamics may reflect treatment sensitivity and could help identify chemotherapy-resistant patients earlier than conventional approaches.”
Nearly half of evaluable patients (47%) achieved sustained ctDNA clearance by the end of treatment. Notably, none of these patients experienced recurrence during follow-up. By contrast, recurrence occurred in 62.5% of patients who did not achieve ctDNA clearance, with a median recurrence-free survival of just 3.5 months after completing therapy.
“This finding suggests that ctDNA clearance, particularly if sustained, can be prognostic of patient outcomes,” Dr. O’Brien said. “In our cohort, patients who achieved and maintained ctDNA clearance during treatment did not recur during the follow-up period, which raises the possibility that ctDNA clearance could serve as a predictive biomarker of treatment response in addition to being prognostic at the end of therapy. These results support the idea that ctDNA monitoring could eventually play a role in identifying patients at very low risk of recurrence.”
The findings also highlighted differences in platinum sensitivity. Patients with persistent ctDNA positivity were more likely to have platinum-resistant or refractory disease, while one patient with platinum-sensitive recurrence demonstrated transient ctDNA clearance before becoming positive again at recurrence, suggesting ctDNA may capture evolving tumor biology in real time.
For clinicians, these insights could help address known limitations of current monitoring tools.
“For clinicians treating patients with stage III or IV ovarian cancer, longitudinal ctDNA testing could complement existing tools by providing a more sensitive and specific, noninvasive measure of treatment response and recurrence risk,” Dr. O’Brien said. “While CA-125 and imaging remain standard in clinical practice, both have limitations, particularly in detecting microscopic residual disease or early recurrence detection. Serial ctDNA testing may help identify patients with persistent disease, guide timing of imaging during surveillance or maintenance, resolve indeterminate findings, serve as a real-time biomarker of treatment response, and detect recurrence earlier than current surveillance methods.”
Although promising, the approach remains investigational. Dr. O’Brien emphasized the need for larger, prospective validation studies to confirm the reproducibility and clinical utility of ctDNA dynamics. Dr. O’Brien is presenting preliminary results from a larger study (Dr. Arend, PI) that is currently ongoing; therefore, as more data become available, they expect to see real statistical and clinical significance, she said.
“A larger prospective cohort study is currently open and enrolling patients to confirm that longitudinal ctDNA dynamics are reproducible and independently associated with platinum response, recurrence risk, and survival. It would also be important to define the optimal testing time points and determine how ctDNA can best inform treatment decisions. One limitation of this study is that it is a single institution. All specimens are prospectively collected and stored in the Arend lab at UAB, and we welcome additional sites and collaborations,” Dr. O’Brien said.
“While there are several use cases for ctDNA in clinical care today, I think utility data demonstrating improved survival are needed before it becomes fully part of routine care,” she added. “That would likely require prospective interventional studies showing that ctDNA-guided surveillance can safely decrease scans and detect recurrence earlier with high specificity, or treatment decisions to stratify patients for escalation/de-escalation strategies and do so in a clinically meaningful and cost-effective way. Standardization of assay performance, thresholds for positivity and clearance, and demonstration of clinical utility would all be necessary before widespread adoption.”
Taken together, the data suggest that ctDNA clearance — and its trajectory over time — could emerge as a powerful tool to refine risk stratification and personalize care for patients with advanced ovarian cancer.
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