Gene-Based Blood Test Accurately Predicts Tumor Recurrence of Advanced Skin Cancer

Melanoma, an aggressive form of skin cancer, becomes extremely difficult to treat once it spreads to other parts of the body. For patients with metastatic melanoma tumors that cannot be surgically removed or are considered unresectable, the wait time for determining the success of drug treatments can be long—typically requiring three months before an X-ray, CT scan, or other diagnostic measures can reveal whether the tumor is shrinking or growing. Researchers have long sought more effective methods for monitoring cancer progression through blood tests, also known as biomarkers, which can be performed more frequently, inexpensively, and conveniently than imaging scans or surgeries, offering a clearer view of how tumors behave over time. One commonly used biomarker in melanoma, lactate dehydrogenase (LDH), is not highly effective, as its levels can also rise due to non-cancerous conditions like liver damage and bone injury. Although other cancer types like prostate, breast, and colon have specific biomarkers, a reliable biomarker for melanoma has remained elusive—until now. A new blood test that monitors DNA fragments released by dying tumor cells could serve as an accurate early indicator of treatment success in advanced melanoma, as detailed in a study published in The Lancet Oncology.

The study, led by researchers at NYU Grossman School of Medicine (New York, NY, USA), focused on adults with metastatic melanoma tumors that could not be surgically removed or were unresectable. The patients had undetectable levels of circulating tumor DNA (ctDNA) after four weeks of drug treatment. The results showed that patients who had undetectable ctDNA levels lived nearly twice as long without disease progression as those who continued to show detectable levels of ctDNA. The researchers noted that early intervention could potentially save lives, particularly in a fast-progressing disease like melanoma, and that blood tests providing quick feedback could be crucial for treatment decisions. Earlier studies by the same team had suggested ctDNA as a promising candidate, as this method focuses on the common genetic mutations in melanoma cells. As these cells break down, the mutated DNA spills into the bloodstream, which can then be detected. Previous smaller studies had shown that this blood test outperformed LDH in predicting melanoma recurrence and tracking the progression of various cancers.

This study, conducted over two years, represents the largest analysis to date of using ctDNA as a tool in skin cancer detection. The researchers analyzed blood samples from two pivotal clinical trials involving 383 participants from the U.S., Europe, and Australia, all of whom were receiving treatment with the drugs dabrafenib and trametinib for unresectable melanoma tumors with mutations in the BRAF gene, present in about 50% of melanoma patients. The team measured ctDNA levels before treatment and one month into therapy. Periodic CT scans were used for further monitoring throughout the trial.

One key finding of the study was that patients with 64 or fewer copies of ctDNA per milliliter of blood before starting treatment tended to have favorable responses to therapy, surviving nearly three years on average. In contrast, patients with higher levels of ctDNA had significantly worse survival outcomes, living for just over a year. The researchers found the blood test to be highly reliable, with ctDNA detected in 93% of patients. These results were also confirmed in a second group of patients from another clinical trial with similar disease stages. Although the blood test has not yet been approved by the U.S. Food and Drug Administration (FDA), the researchers believe the evidence of its accuracy and potential for clinical use supports the need for future approval. Next, the team plans to assess the ctDNA approach in patients with earlier-stage melanoma.

“Although this gene-based test focuses on tumors with BRAFV600 mutations, we believe it will be similarly useful for melanomas that have other mutations, such as defects in the NRAS and TERT genes, which are also commonly mutated in this disease,” said study lead author Mahrukh Syeda, MS. “Ultimately, we’d like to see this test used routinely in the clinic to help guide treatment decisions.”