Research Summary:
Accurate prognostic assessment in patients with cutaneous melanoma is essential as it is one of the most prevalent malignancies in the United States. The American Joint Committee on Cancer (AJCC) staging system remains the cornerstone of risk stratification, but outcomes vary widely among patients with similar clinicopathologic features. Gene expression profiling assays have been developed to complement existing prognostic tools by identifying patients at increased risk for recurrence or metastasis. The 31-gene expression profile (31-GEP) test classifies patients into risk categories for recurrence, distant metastasis, and melanoma-specific mortality. Despite growing evidence supporting its clinical validity, differences in how the 31-GEP test should be used in clinical practice persist. On April 16, 2025, an expert consensus panel convened to review the literature on the 31-GEP test and to develop guidance on its appropriate clinical use in cutaneous melanoma.1
A panel of 10 dermatologists was assembled to review the role of the 31-GEP assay in patient management. Literature was systematically reviewed to identify studies evaluating the analytical validity, clinical validity, and utility of the 31-GEP test; 150 articles were identified, and 26 articles were selected for inclusion. The panel developed nine consensus statements, all receiving unanimous 10 out of 10 approval votes. Consensus statements were organized by strength of recommendation, with Strength of Recommendation Taxonomy (SORT) Level A indicating a recommendation backed by consistent, good-quality, patient-oriented evidence.
Multiple studies demonstrated clinical efficacy for the 31-GEP test and provided consistent and accurate prognostic information for invasive melanoma (SORT Level A), with a recent meta-analysis finding that in 13 studies including 14,760 patients, the 31-GEP test consistently stratified patients into risk groups with five-year melanoma-specific survival (MSS) rates of 99.8 percent for 31-GEP Class 1A (low risk), 97.6 percent for Class 1B/2A (intermediate risk), and 83.4 percent for Class 2B (high risk).
Studies have shown clinical utility for the 31-GEP test for providing prognostic information for invasive melanoma (SORT Level A); one study reported that after receiving 31-GEP results, 50.6 percent of patients experienced a change in management plans.
Studies have shown clinical efficacy for the 31-GEP test in providing prognostic information for invasive melanoma when the thickness or other traditional factors are unknown (SORT Level A), as information about clinicopathologic features available for patients commonly varies, affecting staging assessment and clinical management.
Integration of 31-GEP testing with traditional staging methods can inform the decision to recommend sentinel lymph node biopsy (SLNB) (SORT Level A). Various studies have shown that use of the integrated 31-GEP (i31-SLNB) can reduce the number of unnecessary SLNBs.
There is a statistically significant improvement in assessing prognosis when adding 31-GEP results to AJCC staging (SORT Level A), as one retrospective, multicenter study2 found that in the combined Stage I to III cohort, the addition of 31-GEP results significantly stratified MSS (p<0.001), with Class 1A patients having a higher five-year MSS compared to Class 2B patients (98.7% vs. 77.8%).
The i31-SLNB test is more accurate and precise than online nomograms in predicting the need for SLNB (SORT Level A), with one study finding that the i31-SLNB test identified significantly more patients with T1 to T2 tumors as having less than five-percent risk of sentinel lymph node positivity compared to the Melanoma Institute of Australia nomogram (28.5% vs. 0.9%; p<0.001).
Patients who have received 31-GEP testing have improved MSS and overall survival in comparison to patients who have not received 31-GEP testing (SORT Level A), with one study linking data from Surveillance, Epidemiology, and End Results (SEER) registries to 31-GEP testing results and finding that patients who received 31-GEP testing had a 29 percent lower melanoma-specific mortality (hazard ratio [HR]: 0.71) and a 17 percent lower overall mortality (HR: 0.83) compared to those who did not have 31-GEP testing.3
Patients might be more likely to be receptive to receiving 31-GEP test data when discussing their invasive melanoma and management (SORT Level C). The limited research on this topic suggests that patients find 31-GEP test results beneficial.
The existing data support the use of 31-GEP testing as a best practice for the appropriate patient with melanoma (SORT Level A), with the panel unanimously concluding that the 31-GEP test is most beneficial for patients with T1a high risk tumors, T1b to T3 tumors, and patients with sentinel lymph node negative results.
Following a review of existing literature, this panel agreed that there is strong support for the use of 31-GEP testing to provide prognostic information for invasive melanoma, as the 31-GEP test has been shown to provide robust prognostic information, statistically improve prognosis assessment when added to AJCC staging, and patients who have received the test have improved melanoma-specific mortality and overall survival. The panel believes that the existing literature strongly supports the utilization of 31-GEP testing as a best practice for appropriate patients with cutaneous melanoma.
References
- Burshtein J, Cockerell C, Cotter D, et al. 31-gene expression profiling for cutaneous melanoma: an expert consensus panel. Derm Online J. 2025. In Press.
- Wisco OJ, Marson JW, Litchman GH, et al. Improved cutaneous melanoma survival 460 stratification through integration of 31-gene expression profile testing with the American Joint Committee on Cancer 8th Edition Staging. Melanoma Res. 2022;32(2):98–102.
- Bailey CN, Martin BJ, Petkov VI, et al. 31-gene expression profile testing in cutaneous 498 melanoma and survival outcomes in a population-based analysis: a SEER collaboration. JCO Precis Oncol. 2023;(7):e2300044.