Dynamic Monitoring of Recurrent Ovarian Cancer Using Serial ctDNA: A Real-World Case Series

TL;DR

This study shows that measuring cancer DNA in the blood (ctDNA) can help detect ovarian cancer recurrence earlier than traditional methods in some cases.

Contribution

The study demonstrates the real-world clinical utility of serial ctDNA monitoring in recurrent ovarian cancer patients.

Findings

ctDNA levels generally reflected clinical status and accurately mirrored disease progression and treatment response.

In one case, ctDNA detected cancer recurrence four months before CT scans or blood tests.

Some patients showed clinical progression with undetectable ctDNA, highlighting limitations in sensitivity or biological factors.

Abstract

Ovarian cancer often comes back after the first treatments, but it is hard to detect and monitor in time. Tests like CT scans and blood tests (CA-125) are not always accurate in showing if or when the cancer returns or grows. In this study, we tested whether measuring pieces of cancer DNA found in the blood (circulating tumor DNA or ctDNA) could help detect ovarian cancer earlier and better. We collected serial blood samples from patients over time and found that changes in ctDNA usually matched closely with whether the patient’s cancer was growing or responding to treatment. In one case ctDNA even gave warnings of the cancer returning many months before it could be seen on CT scans or blood tests. However, in a few cases, ctDNA did not show cancer growth. These results suggest that using ctDNA could help make personalized decisions about treatment in ovarian cancer.

Recurrent ovarian cancer (OC) is challenging to detect early using current methods like CA-125 and imaging. Circulating tumor DNA (ctDNA) may improve disease monitoring. Here, we assess the real-world clinical utility of serial ctDNA analyses in patients with recurrent OC. We analyzed serial plasma samples (N = 23) from six patients with recurrent OC using a tumor-informed next-generation sequencing assay targeting 68 cancer-related genes developed at the University of Washington. ctDNA variant allele frequencies (VAFs) were correlated with CA-125 levels, radiographic findings, and clinical outcomes. ctDNA levels generally reflected clinical status, accurately mirroring disease progression and therapeutic response. In one patient, rising ctDNA preceded clinical recurrence by four months, despite normal CA-125 and imaging, highlighting its potential advantage. Conversely, some patients exhibited clinical progression with undetectable ctDNA, indicating limitations in assay sensitivity, biological factors, or metastatic sites (e.g., brain metastases). ctDNA and CA-125 showed complementary value in most cases, suggesting potential combined use in clinical monitoring. Our findings demonstrate that ctDNA is a promising biomarker to complement existing monitoring approaches for recurrent OC. In some cases, capable of predicting relapse and treatment response ahead of current clinical indicators. However, identified discordances underscore technical and biological challenges that warrant further investigation. Larger prospective studies are necessary to refine ctDNA’s clinical utility and integration into personalized OC care.

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