Results from a new clinical trial, recently published in JAMA Surgery, suggest that a gene-based assay could help physicians better assess the risk of cancer spread in patients with early-stage melanoma, potentially sparing some patients from unnecessary surgery.
The study, which included investigators from the Duke Cancer Institute (DCI), is the first prospective clinical trial to evaluate whether a molecular gene signature can improve risk stratification for patients whose melanoma is otherwise considered early-stage based on traditional staging methods.
Melanoma continues to rise in incidence, and most patients are diagnosed at an early stage of disease. Standard melanoma staging relies on the tumor, node, metastasis (TNM) system, which classifies tumors based on size, lymph node involvement, and whether the cancer has spread to distant organs.
While TNM staging is useful, it does not always capture how aggressive a tumor may be. Some patients diagnosed with stage I melanoma still experience disease recurrence or lymph node spread, outcomes that are not fully explained by traditional clinical and pathologic features alone.
“By relying only on conventional staging, we may be missing some of the ‘bad actors,’” said Georgia Beasley, MD, DCI surgical oncologist and co-investigator on the trial. “Other cancers, like breast cancer, have increasingly incorporated gene-based tools to help better predict risk, and melanoma has lagged behind in that regard.”
The trial evaluated a gene expression assay known as the Merlin test, which analyzes tumor tissue from a patient’s initial melanoma biopsy. The assay combines genetic information from the tumor with established clinical features to generate a personalized risk estimate for lymph node spread.
Unlike previous studies, which examined gene signatures retrospectively, this was the first large, prospective clinical trial to test whether such an approach could meaningfully add to existing risk prediction for early-stage melanoma patients.
One of the most immediate potential benefits of the test is its ability to help guide surgical decision-making, particularly regarding whether a patient should undergo sentinel lymph node biopsy, a procedure that requires anesthesia and carries some risk of complications.
This consideration is especially relevant for older patients or those with additional medical conditions.
“If we have a tool that tells us a patient’s likelihood of lymph node involvement is very low, we may be able to safely avoid more aggressive surgery,” Beasley said. “That means avoiding anesthesia, reducing complications, and overall lowering the burden of treatment.”
For both patients and physicians, the test may help reduce uncertainty. While many patients understandably want to pursue every available intervention, having a reliable, personalized risk estimate could make it easier to choose less invasive options when appropriate.
Following publication of the trial results, the Merlin assay is now commercially available and can be ordered by physicians, including those at Duke, for selected patients.
Beasley noted that this represents an important step toward integrating molecular risk tools into everyday melanoma care. However, she emphasized that further refinements are needed to improve efficiency, particularly in how tumor samples are handled.
“Right now, the process still involves shipping glass pathology slides, which can slow things down,” Beasley said. “Ideally, this would all move to a digital platform so results could be generated faster and patients wouldn’t have to wait weeks for answers.”
Work is already underway to streamline and digitize parts of this process, with the goal of delivering timely information that can better inform real-time treatment decisions.
While biomarkers and risk assessment tools may not draw the same attention as novel cancer drugs, Beasley emphasized that their impact on patient care can be substantial.
“These kinds of studies are incredibly important, even if they’re not flashy,” she said. “They help patients, families, and physicians make better decisions, and that’s something that’s often underestimated.”
