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A recent study reveals that monitoring blood levels of circulating tumor DNA (ctDNA) from dying cancer cells could serve as an effective method for predicting the recurrence of skin cancer, specifically melanoma.
The research, undertaken by NYU Langone Health and the Perlmutter Cancer Center, found that around 80% of patients with stage III melanoma exhibited detectable levels of ctDNA before initiating treatment aimed at controlling their tumors. These individuals were notably more likely to experience cancer recurrence compared to those whose ctDNA levels were not detectable.
Furthermore, the study indicated that the speed of recurrence was more than four times faster in patients with detectable ctDNA levels, with a direct correlation observed: the higher the levels of ctDNA, the quicker the cancer returned.
Lead author Mahrukh Syeda, MS, emphasized the findings, stating, “Our research indicates that ctDNA testing could assist oncologists in identifying melanoma patients who are likely to respond positively to treatment.” Syeda, a research scientist in the Ronald O. Perlman Department of Dermatology at NYU Grossman School of Medicine, expressed her hope that such assessments will soon be integrated into routine clinical practice to guide treatment choices.
Additionally, nearly all patients who had detectable ctDNA levels at various intervals—three, six, nine, or 12 months into treatment—experienced a return of melanoma. Thus, if ctDNA becomes detectable after therapy has started, it could suggest that the disease is progressing.
Stage III melanoma is recognized as an aggressive form of skin cancer, characterized by the spread of tumor cells from the skin to adjacent lymph nodes. After surgical removal of these lymph nodes, identifying recurrence through traditional imaging techniques, such as X-rays and CT scans, can be challenging. This limitation has intensified the search for more effective early detection methods.
Syeda highlighted the importance of tracking treatment efficacy and detecting early signs of cancer progression, particularly for melanoma, which is notoriously difficult to manage once it metastasizes. An early indication from ctDNA analysis could potentially prove life-saving.
This ctDNA testing method targets frequent mutations present in melanoma cells, which leak into the bloodstream as the cells die off. Previous studies have successfully utilized ctDNA tests to monitor the progression of various cancers, including colorectal and breast cancers. In a related 2021 study, researchers linked higher ctDNA levels in stage IV melanoma—where the cancer has extensively spread—to reduced survival rates, and noted that changes in ctDNA during treatment could help differentiate patients likely to have better or worse outcomes.
The findings from this latest research, published online on April 15 in the journal The Lancet Oncology, represent the most comprehensive investigation of ctDNA as a predictive tool for recurrence in stage III melanoma patients, according to Syeda.
The study analyzed blood samples from nearly 600 participants involved in a prior clinical trial across Europe, North America, and Australia. Researchers measured ctDNA levels and compared these with clinical signs of cancer recurrence while accounting for other influential factors like age, sex, and treatment type in their statistical models.
Importantly, the results indicated that ctDNA analysis was at least as effective, if not superior, in predicting recurrence compared to other experimental approaches that analyze tumor tissue, including tests measuring immune response within cancer cell clusters.
Senior study author, dermatologist David Polsky, MD, PhD, remarked on the advantages of ctDNA testing, stating, “While traditional tissue-based tumor analyses can only estimate recurrence likelihood, ctDNA tests directly measure disease presence, providing a clear indication of melanoma recurrence.” Polsky holds the Alfred W. Kopf, M.D., Professorship in Dermatologic Oncology in the Ronald O. Perelman Department of Dermatology.
However, Polsky cautioned that some patients still experienced recurrence despite having negative ctDNA test results before treatment began. To enhance the sensitivity of their ctDNA method, the authors plan to further refine their testing approach. They also aim to investigate clinically whether employing this biomarker for treatment decisions can lead to improved survival rates and enhanced quality of life for patients.
The study received funding from Novartis Pharmaceuticals Corporation in East Hanover, New Jersey. Polsky serves on advisory boards for both Novartis and Merck and has accepted honoraria from several medical education organizations, as well as laboratory research contracts from various pharmaceutical companies. All relationships are being managed according to the policies and standards of NYU Langone Health.
In addition to Syeda and Polsky, the research team included Jennifer Wiggins-Crosby, PhD, and Saim Ali, BA, from NYU Langone Health, alongside contributors from prestigious institutions worldwide, including the University of Sydney, University of Queensland, and the National Cancer Institute of Milan, among others.
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