Two recent presentations at major surgical oncology and melanoma research conferences have shed light on the evolving role of gene expression profile (GEP) testing in guiding sentinel lymph node biopsy (SLNB) decisions for patients with cutaneous melanoma. While one study demonstrated promising results, the other revealed limitations, underscoring the need for careful interpretation and application of these tests.
DECIDE Trial Shows Positive Results for DecisionDx-Melanoma
At the Society of Surgical Oncology Annual Meeting in March 2024, J. Michael Guenther, MD, presented updated findings from the DECIDE trial, a prospective, multicenter study evaluating the i31-GEP (DecisionDx-Melanoma) test. The trial assessed the test's ability to inform SLNB decision-making in patients with T1-T2 cutaneous melanoma.
The results indicated that in 322 patients with T1a-T2b cutaneous melanoma, those with a less than 5% i31-GEP SLNB test result who proceeded with SLNB had a 0% SLN positivity rate. Furthermore, with a median follow-up of two years, no class 1A (low-risk) patients experienced recurrence or distant metastasis. These data confirm that DecisionDx-Melanoma can accurately identify patients with a low risk of SLN positivity and a low likelihood of disease progression. Notably, approximately 18% of patients forwent SLNB based on DecisionDx-Melanoma test results without experiencing recurrence or metastasis.
MERLIN_001 Trial Fails to Meet Primary Endpoint
In contrast, the MERLIN_001 trial, presented by Vernon Sondak, MD, at the Society for Melanoma Research Congress in October 2024, did not meet its primary objective. This prospective multicenter registry study aimed to validate the MERLIN CP-GEP test in predicting sentinel node status in T1-T3 cN0 melanoma. The study evaluated 1686 patients who underwent SLNB after experimental MERLIN testing, with surgeons and patients blinded to the results.
The primary endpoint, defined as a SLN positivity rate of less than 5% in the low-risk CP-GEP test group, was not achieved. The actual SLN positivity rate in this group was 7.1%, exceeding the predefined threshold. While subsequent subanalyses showed slightly lower positivity rates in stage IB patients (6.4%) and patients aged 65 and older (6.2%), these findings are considered exploratory due to the failure to meet the primary endpoint. The study indicates that the MERLIN CP-GEP test, as evaluated in this trial, did not reliably identify patients with a sufficiently low risk to safely forgo SLNB.
Implications for Clinical Practice
Both presentations underscore the ongoing research and evolving understanding of GEP tests in melanoma management. The positive results from the DECIDE trial reinforce the clinical utility of DecisionDx-Melanoma in identifying low-risk patients who may consider forgoing SLNB. However, the MERLIN_001 trial highlights the importance of validating GEP tests in prospective studies and understanding their limitations.
The differing outcomes also emphasize that not all GEP tests are created equal. As with GEP tests used in breast and prostate cancers, different tests for melanoma can exhibit clinically different performance characteristics. Clinicians should carefully consider the specific study designs and validation data for each test when interpreting results and making treatment decisions.
Further research and publication of the full results from both the DECIDE and MERLIN_001 trials are anticipated in 2025, which should provide additional clarity on the optimal use of GEP tests in melanoma management.
