A large multicenter clinical trial published in JAMA Surgery shows that a gene expression profile–based test can reliably identify melanoma patients who have a low risk of cancer spreading to their lymph nodes. The findings could help guide decisions about whether to perform sentinel lymph node biopsy, a standard but invasive staging procedure.
The MERLIN_001 trial evaluated the clinicopathologic gene expression profile test in more than 1,700 patients with early-stage melanoma at nine U.S. cancer centers, including Moffitt Cancer Center . The blinded, prospective study found that the test accurately stratified patients by their likelihood of having sentinel lymph node metastasis, a key factor in treatment planning and prognosis.
"This study represents a major step forward in evaluating personalized melanoma care," said Vernon Sondak, M.D. , principal investigator and chair of the Cutaneous Oncology Department at Moffitt. "Our results show that the clinicopathologic gene expression profile test adds a level of accuracy above current clinical factors alone, even when factors like mitotic rate and histologic subtype are taken into account, and this kind of knowledge ultimately allows patients and surgeons to make better decisions about when sentinel node biopsy should be part of the management of clinically localized melanoma. In appropriately selected patients, this test can add value for shared decision-making."
Refining Risk to Inform Surgical Decisions
Current melanoma guidelines recommend sentinel lymph node biopsy for patients with a predicted risk of nodal metastasis greater than 10%, and consider the procedure when the risk is between 5% and 10%. The clinicopathologic gene expression profile test combines a gene signature with clinical factors such as tumor thickness and patient age to classify risk as low or high.
In the trial:
37% of patients were classified as low risk by the test.
The rate of sentinel node positivity among low-risk patients was 7.1%, compared with 23.8% in the high-risk group.
Negative predictive value for low-risk cases was 92.9%.
The test performed consistently across tumor sites, histologic subtypes and age groups.
Nearly half of patients aged 65 or older were classified as low risk, with a 6.6% nodal positivity rate, more than three times lower than high-risk cases.
Potential to Reduce Unnecessary Surgeries
Sentinel lymph node biopsy is used to guide treatment decisions, including the use of adjuvant immunotherapy and surveillance intensity. However, the procedure adds cost, potential complications and recovery time for patients who may not benefit. A predictive test could help reduce the number of node-negative sentinel lymph node biopsies performed each year without compromising patient outcomes.
"This trial marks a milestone in our ability to personalize melanoma treatment by integrating gene expression profile testing with clinical decision-making," said Jonathan Zager, M.D. , contributing author of the study and surgical oncologist in the Cutaneous Oncology Department at Moffitt. "By helping identify who's truly low risk for lymph node metastasis, the Merlin assay allows us as clinicians to make more informed, evidence-based choices and potentially spare some patients an unnecessary procedure and the general anesthesia that goes along with it."
About the Study
The MERLIN_001 trial was sponsored by SkylineDx and conducted at nine U.S. melanoma centers. Patients with T1b–T3b melanoma (and high-risk T1a) were enrolled between September 2021 and June 2024. All underwent sentinel lymph node biopsies, and clinicopathologic gene expression profile testing was performed on archived biopsy tissue. Neither patients nor investigators knew the results during treatment. This research builds on prior retrospective and small prospective studies of gene expression profile-based testing and underscores its potential role in guideline discussions around sentinel lymph node biopsy.
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 57 National Cancer Institute-designated Comprehensive Cancer Centers
