A gene expression profile–based test coupled with clinicopathologic factor assessment was able to consistently identify patients with melanoma who were at a low risk for their disease spreading to the sentinel lymph nodes, according to findings from the MERLIN_001 trial published in JAMA Surgery.
“This study represents a major step forward in evaluating personalized melanoma care,” said principal investigator Vernon Sondak, MD, 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, 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.”
Background and Study Methods
Guidelines recommend a sentinel lymph node biopsy for patients with melanoma who have a predicted risk of sentinel lymph node metastasis of more than 10%, and suggest that sentinel lymph node biopsy be considered for patients with a risk of 5% to 10%.
Researchers wanted to determine if a gene expression profile–based test combined with clinicopathologic factors could help to predict the possibility of a positive sentinel lymph node biopsy in patients with T1 to T3 melanoma in order to guide which patients should undergo biopsy or not.
They conducted the blinded, multicenter, prognostic MERLIN_001 study between September 2021 and June 2024 and enrolled patients with biopsy-proven invasive cutaneous melanoma with T1 to T3 tumor stage and clinically negative regional lymph nodes. Gene expression profile testing was performed on tissue from the primary melanoma biopsy to determine risk for a positive sentinel lymph node biopsy.
Key Study Findings
A total of 1,761 patients underwent sentinel lymph node biopsy, with 17.6% having positive sentinel lymph nodes. Gene expression profile testing was completed successfully in 97.7% of samples.
Thirty-seven percent of patients were considered low risk by gene expression profile testing plus clinicopathologic factor assessment, and 7.1% of these patients were sentinel lymph node–positive. The negative predictive value of the gene expression profile testing was 92.9% (95% confidence interval [CI] = 90.7%–94.8%).
Fewer low-risk cases were found by increasing T category according to gene expression profile testing plus clinicopathologic factors: 68.2% of patients with T1 tumors were found to be low risk, 32.9% of T2 tumors, and 2.8% of T3 tumors.
Among high-risk patients, 23.8% were found to be sentinel lymph node–positive, amounting to an almost threefold increase from that of low-risk cases.
The gene expression profile test and clinicopathologic factors was consistently able to identify sentinel lymph node–positive cases across primary sites, histologic subtypes, and mitotic counts.
“This trial marks a milestone in our ability to personalize melanoma treatment by integrating gene expression profile testing with clinical decision-making,” said contributing study author Jonathan Zager, MD, Surgical Oncologist in the Cutaneous Oncology Department at Moffitt Cancer Center. “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.”
Disclosure: The trial was sponsored by SkylineDx. For full disclosures of the study authors, visit jamanetwork.com.
