Gene Expression Test Reduces Need for Invasive Lymph Node Biopsies in Early-Stage Melanoma Patients
核心洞察
A large multicenter trial involving nearly 1,800 melanoma (搜索) patients demonstrated that a gene expression profile test can accurately identify patients with low risk of lymph node metastasis (搜索).
The test classified 37% of patients as low risk, with only 7.1% of these patients having cancer in their lymph nodes compared to 23.8% in the high-risk group.
The findings could help reduce unnecessary sentinel lymph node biopsies, sparing patients from invasive surgery while maintaining treatment accuracy.
A large multicenter clinical trial has demonstrated that a gene expression profile-based test can reliably identify melanoma (搜索) patients with low risk of cancer spreading to their lymph nodes, potentially reducing the need for invasive surgical procedures. The MERLIN_001 trial, published in JAMA Surgery, evaluated more than 1,700 patients with early-stage melanoma across nine U.S. cancer centers and found that the test accurately stratified patients by their likelihood of sentinel lymph node metastasis (搜索).
Clinical Trial Results Show Strong Predictive Accuracy
The blinded, prospective study found that 37% of patients were classified as low risk by the clinicopathologic gene expression profile test. Among these low-risk patients, only 7.1% had positive sentinel lymph nodes, compared with 23.8% in the high-risk group. The test achieved a negative predictive value of 92.9% for low-risk cases, meaning that approximately 93% of patients classified as low risk had no cancer in their lymph nodes.
"This study represents a major step forward in evaluating personalized melanoma (搜索) care," said Vernon Sondak, M.D., principal investigator and chair of the Cutaneous Oncology Department at Moffitt Cancer Center. "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."
Addressing Current Treatment Challenges
Current melanoma (搜索) 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%. However, nearly 80% of people who undergo lymph node biopsy have no cancer in their lymph nodes, highlighting the need for better risk stratification tools.
The Merlin CP-GEP (搜索) test measures the activity of eight genes (搜索) in melanoma (搜索) tumors and combines this genetic signature with clinical factors such as tumor thickness and patient age to classify risk as low or high. The test performed consistently across tumor sites, histologic subtypes, and age groups throughout the trial.
Potential Impact on Elderly Patients
The study revealed particularly promising results for older patients. 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. This finding could be especially significant given that elderly patients may face higher surgical risks.
Reducing Surgical Burden
Sentinel lymph node biopsy is currently 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 from it.
"By helping identify who's truly low risk for lymph node metastasis (搜索), 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," said Jonathan Zager, M.D., contributing author and surgical oncologist in the Cutaneous Oncology Department at Moffitt.
Study Design and Validation
The MERLIN_001 trial was sponsored by SkylineDx (搜索) and conducted between September 2021 and June 2024. Patients with T1b–T3b melanoma (搜索) (and high-risk T1a) were enrolled, and all underwent sentinel lymph node biopsies. The gene expression profile testing was performed on archived biopsy tissue, with neither patients nor investigators knowing the results during treatment.
Lead researcher Dr. Tina Hieken, a surgical oncologist at the Mayo Clinic Comprehensive Cancer Center (搜索), emphasized the precision medicine aspect of the findings: "This test lets us use a patient's own tumor biology to guide care with true precision."
The research builds on prior retrospective and small prospective studies of gene expression profile-based testing and represents a significant advancement in personalized melanoma (搜索) treatment approaches. The Merlin CP-GEP (搜索) test is already available in the United States, potentially allowing for immediate clinical implementation of these findings.