Nov. 08, 2025
A recent multicenter clinical trial based on research developed by Mayo Clinic experts provides valuable new insights into the management of early- and intermediate-stage cutaneous melanoma. The research, published in JAMA Surgery, evaluated the Merlin CP-GEP test, a gene expression profile-based assay designed to predict sentinel lymph node (SLN) metastasis risk, potentially sparing patients from unnecessary lymph node surgery.
Rethinking risk in melanoma management
Treatment decisions for melanoma hinge on accurately assessing the risk of lymph node involvement. SLN biopsy (SLNB) has long been the standard for staging, yet in nearly 80% of patients who undergo the procedure, the biopsy finds no cancer in the nodes. The Merlin CP-GEP test, which analyzes eight genes from the initial tumor biopsy alongside patient age and tumor thickness, offers a new pathway for personalized care.
"While surgery remains central to melanoma management, our data show that genomic testing can help identify selected patients who may safely avoid SLNB," says Tina J. Hieken, M.D., a surgical oncologist at Mayo Clinic Rochester and co-first author of the study. "This approach allows us to tailor care based on the biology of each patient's tumor."
Genomic profiling refines melanoma staging and surgical decision-making
The Merlin trial enrolled 1,761 patients across nine U.S. cancer centers between 2021 and 2024, marking the largest prospective evaluation of gene expression profiling for melanoma to date. The Merlin CP-GEP test demonstrated consistent performance across tumor sites, histological subtypes and age groups and was successful in 97.7% of samples. About 93% of people classified as low risk had no cancer in their lymph nodes, while about 25% in the high-risk group did.
The test is most impactful for patients with clinical stage 1B melanoma and those age 65 and older, where low-risk results correlated with less than 10% risk of node metastasis. For patients with higher risk tumors (T2b, T3), SLNB remains an appropriate option, as few of these tumors are classified as low risk by the test.
"Many molecular tests for melanoma were introduced before we fully understood how to interpret them in clinical practice, says Alexander Meves, M.D., M.B.A., a dermatologist at Mayo Clinic Rochester and co-developer of the test. "What sets the Merlin program apart is that we first generated prospective, blinded, multi-institutional evidence. This helps surgeons to understand what a low- or high-risk result indicates, who will benefit, and how to apply it in shared decision-making. That level of scientific rigor is what ultimately enables responsible adoption."
Integrating genomic testing into shared decision-making
The authors call for ongoing research to refine selection criteria and further validate the role of the test in clinical practice. Incorporating genomic testing into melanoma care may optimize outcomes, reduce morbidity and support more-nuanced, multidisciplinary decision-making.
"This study provides a framework for incorporating genomics into clinical care," says Dr. Hieken. "It's about using precision medicine to guide the right choice for each patient and personalizing the pathway to cure."
For more information
Hieken TJ, et al. Gene expression profile-based test to predict melanoma sentinel node status: The MERLIN_001 study. JAMA Surgery. In press.
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