TOPLINE:

A test that combines clinicopathologic factors and a tumor’s gene expression profile (CP-GEP) reliably identified patients with a less than 10% risk for a positive sentinel lymph node biopsy — though it did not meet the less than 5% upper CI threshold for low-risk patients. Rates of sentinel lymph node metastasis were threefold higher in patients classified as high risk than in those deemed low risk.

METHODOLOGY:

• Guidelines recommend sentinel lymph node (SLN) biopsy for patients with melanoma when the predicted risk for SLN metastasis exceeds 10% and consideration of biopsy when the risk is 5%-10%. Recently, gene expression profiling has attracted interest to more precisely estimate SLN metastasis risk. Several GEP-based tests are commercially available, but large-scale prospective studies are lacking.
• To address this, researchers conducted a prognostic study at nine academic medical centers, enrolling 1761 patients (median age, 64 years; 56.6% male) with biopsy-proven invasive cutaneous melanoma (T1-T3 tumors) and clinically negative regional lymph nodes.
• Primary biopsy tissues were subjected to CP-GEP testing (the commercially available Merlin Assay), with results reported as low risk or high risk. SLNs were analyzed using standard institutional protocols and considered positive for metastasis if any malignant cells were identified.
• Researchers determined the observed rate of SLN metastasis, the negative predictive value (1 — the observed rate of SLN metastasis for low-risk cases), and the positive predictive value (the observed rate of SLN metastasis for high-risk cases).

TAKEAWAY:

• Overall, 651 (37.0%) patients were classified as low risk, of whom 46 (7.1%) were SLN-positive — for a negative predictive value of 92.9%. Among high-risk patients, 23.8% were SLN-positive, representing a 3.4-fold higher observed rate than in low-risk patients.
• The proportion of patients classified as CP-GEP low-risk declined with increasing T category: 68.2% (346 of 507) for T1, 32.9% (295 of 897) for T2, and 2.8% (10 of 357) for T3. Across every prespecified subset based on T category and subcategory, clinical stage, age group, mitotic count, and anatomic site, the observed rate of SLN metastasis was consistently lower among CP-GEP low-risk patients than among high-risk patients.
• Among two large patient subsets — those with clinical stage IB tumors (n = 1187) and those aged 65 years or older (n = 832) — 49.3% and 42.1% were classified as low risk, respectively. For low-risk patients with stage IB tumors, the observed sentinel node metastasis rate was 6.5% — threefold lower than that of high-risk patients (18.3%). Similarly, among patients aged 65 years or older, the SLN metastasis rate was 6.6% — threefold lower than that of high-risk patients in the same age group across all clinical stages (20.3%).
• Among the 1.5% (26 of 1761) of patients with clinically high-risk T1a primary tumors, only one (3.8%) had a positive SLN; that patient was one of five CP-GEP high-risk cases, while the other 21 were classified as low risk and had no positive SLNs.
• The trial did not meet its primary objective of identifying low-risk patients where the upper bound of the 95% CI for SLN positivity was less than 5% — meaning CP-GEP results would not exclude a guideline-based surgical referral to discuss SNL biopsy.

IN PRACTICE:

“This prognostic study confirmed that the CP-GEP test could distinguish higher- and lower-risk melanomas and substantiated that the information obtained by the test could help inform the discussion between patient and surgeon about whether to perform SLNB when a 10% threshold of sentinel node metastasis risk is appropriate for surgical decision-making,” the authors of the study wrote. They added that blinded prospective evaluations of GEP-based and other genomic predictive tests are “essential to provide reliable estimations of their clinical utility, and ultimately cost-effectiveness, for selecting patients for SLNB.”

SOURCE:

The study, led by Tina J. Hieken, MD, Mayo Clinic, Rochester, Minnesota, was published online in JAMA Surgery.

LIMITATIONS:

Investigators enrolled surgeon‑selected patients who had already opted for SLN biopsy, which might limit generalizability to all patients with T1-T3 melanoma. Additionally, not all patients were able to have their formalin-fixed, paraffin-embedded tumor block analyzed, and a small number of CP-GEP tests were inconclusive.

DISCLOSURES:

The study was funded by SkylineDx. Hieken disclosed receiving grants from SkylineDx during the conduct of the study and institutional research funding from Genentech outside the submitted work. Several authors reported receiving grants or consulting fees and having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.