A simple blood test tracking circulating tumor DNA (ctDNA) may provide oncologists with a clearer, earlier indication of how patients with advanced ovarian cancer are responding to treatment—and could eventually transform the way clinicians monitor disease and predict recurrence.
The study aimed to investigate whether longitudinal ctDNA testing could serve as a real-time biomarker for both systemic and local treatment response and for recurrence monitoring in advanced-stage ovarian cancer (OC).
Emily O’Brien, MD, a gynecologic oncology fellow at the University of Alabama at Birmingham (UAB), presented the study findings at annual meeting of the Society of Gynecologic Oncology (SGO), held April 9 – 13, 2026, in San Juan, PR, highlighting the ability of ctDNA to provide dynamic risk assessment compared with traditional tools such as CA-125, a tumor biomarker that has been used as the primary ovarian cancer marker for the past four decades. However, blood tests like CA-125, are not always accurate in showing if or when the cancer returns or grows. Researchers believed that ctDNA may improve disease monitoring in a real-world clinical setting of serial ctDNA analyses in patients with recurrent OC. [1][2][3]
Study design
Tissue and plasma samples were prospectively collected from 20 newly diagnosed Stage III/IV OC patients treated between 2022 and 2024. All patients received platinum/taxane-based neoadjuvant chemotherapy (NACT), interval debulking surgery (IDS), and adjuvant chemotherapy (ACT), and all achieved optimal debulking at surgery. The median age was 66 years (range: 46–86), with 25% Stage IV and 75% Stage III. Blood was drawn at four key timepoints: baseline (pre-NACT), post-NACT/pre-IDS, post-IDS, and post-ACT. The Signatera Genome™ assay (Natera, Inc.), designed from whole-genome sequencing of matched tumor and normal blood, was used to detect and quantify ctDNA. Median clinical follow-up was 13.1 months (range: 5.9–30).
Key Results
Of the 20 patients, 15 had adequate matched samples for longitudinal ctDNA analysis. Detection rates of ctDNA dropped from 100% at baseline to 53% after completion of all therapy, mirroring a reduction in tumor burden. More importantly, the pattern of ctDNA changes over time yielded the strongest clinical insights:
- Patients who achieved and maintained ctDNA clearance throughout treatment experienced no recurrence during follow-up.
- Persistent ctDNA positivity throughout therapy was associated with platinum resistance and a median recurrence-free survival of just 3.5 months.
- Recurrence occurred in 45% (9/20) of the cohort, with 62.5% of those who failed to clear ctDNA experiencing relapse.
- One patient with platinum-sensitive recurrence transiently cleared ctDNA, but positivity returned at relapse, illustrating ctDNA’s ability to capture evolving tumor biology.
Clinical Implications and Next Steps
O’Brien underscored that serial ctDNA measurements could help clinicians identify chemotherapy-resistant or high-risk patients earlier than conventional markers. This approach could guide surveillance imaging, resolve indeterminate findings, and enable more personalized follow-up.
Although promising, the approach remains investigational. O’Brien emphasized the need for larger, multi-institutional prospective studies to confirm the clinical utility and reproducibility of ctDNA dynamics. Standardization of assay performance, optimal testing intervals, and positivity thresholds is also essential prior to widespread adoption.
Longitudinal ctDNA monitoring provided early, refined risk stratification in advanced ovarian cancer, supporting its role as a real-time biomarker of treatment response and recurrence risk. Sustained ctDNA clearance may predict platinum sensitivity and improved survival, while persistent positivity identifies patients at high risk for recurrence.
Future research will further define the role of ctDNA in guiding personalized care for patients with ovarian cancer.
Reference
[1] O’Brien E, Edwards C, Scalise CB, Dutta P, Malhotra M, Kalashnikiva E, Parisian A, Hook N, Heilek G, Liu M, Einaggar A, Arend R, Dinkins K. Clinical performance of Signatera Genome assay to predict treatment response in patients with advanced-stage ovarian cancer receiving neoadjuvant chemotherapy, Gynecologic Oncology Volume 208, Supplement, May 2026, Page S453; https://doi.org/10.1016/j.ygyno.2026.02.025
[2] Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MR. CA125 and Ovarian Cancer: A Comprehensive Review. Cancers (Basel). 2020 Dec 11;12(12):3730. doi: 10.3390/cancers12123730. PMID: 33322519; PMCID: PMC7763876.
[3] Rios-Doria E, Reichel JB, Radke MR, Manhardt E, Rubin-Saika M, Lockwood C, Swisher EM, Banda K. Dynamic Monitoring of Recurrent Ovarian Cancer Using Serial ctDNA: A Real-World Case Series. Curr Oncol. 2025 Oct 21;32(10):585. doi: 10.3390/curroncol32100585. PMID: 41149505; PMCID: PMC12563156.
Featured image: Doctor discussing treatment options with a patient. Photo courtesy: © 2019 – 2026 Fotolia/Adobe. Used with permission.
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