Melanoma Updates: Gene Expression Profiling Tests

On the third day of the 2023 AAD Annual Meeting, Douglas Grossman, MD, PhD, FAAD, shared insights and guideline updates during his session, “Update on Gene Expression Profiling (GEP) Tests.”

To start, Dr Grossman went over melanoma prognostics by reviewing a study published in the Cancer Journal for Clinicians which showed clinicopathologic and outcomes data. Key variables included Breslow depth, ulceration, sentinel lymph node (SLN) status, and (micro)satellites, all of which fell under pathologic staging.

Yet, Dr Grossman emphasized that some stage I patients developed metastatic cancer, whereas many stage II and/ or III patients never experience a recurrence. Additionally, there is no reliable predictive factor to identify these patients.

He stressed that this showed there was some value behind molecular prognostic testing, such as:

• improved staging accuracy
• informed decisions on frequency of follow up
• imaging
• adjuvant therapy

Next, he presented prognostic GEP tests, which are meant to identify primary melanomas with high risk of metastasis. He noted that gene expression signatures were significantly associated with melanoma progression and metastasis per a study from 2005. These showed archival tissue with sufficient tumor left cut within multiple slides. Additionally, primary melanoma tumors categorized as “low risk” or “high risk” were based on expression levels consisting of a limited panel of validated genes. He shared that there are 2 tests available:

• Decision Dx-Melanoma (31-GEP) available in the United States
• Melagenix test (8-GEP) available in Europe

He then went over a few studies highlighting the benefits and utilization of each test, starting with 31-GEP. He noted that combining 31-GEP results with the American Joint Committee on Cancer (AJCC) products was shown to enhance sensitivity when compared with each standalone product. He also shared that class 2 GEP results were closely linked to relapse-free survival (RFS) and distant metastasis-free survival (DMFS). Additionally, combining 31-GEP and SLN biopsy (SLNB) was shown to improve sensitivity and negative predictive value for DMFS.

He shared that the 31-GEP test was growing in prevalence, with more than 20% of all invasive melanomas being GEP-tested. This is also being covered by Medicare and Medicaid (roughly costing $7193) for patients aged 65 years or older. He also noted that although there are multiple studies showcasing the impact of the test on clinical decision-making, there are no studies showcasing improved patient outcomes based on the utilization of these test results.

Dr Grossman moved on to SLNB, noting that it is primarily used to determine eligibility for adjuvant therapy and clinical trials. Although roughly 20% or less SLNBs are positive, it remains to be seen if procedures could be avoided in the other 80%. Additionally, a molecular screening test could prove to be valuable in improving the selection of patients for SLNB.

Finally, Dr Grossman shared that prognostic GEP tests are currently not advocated in national guidelines due to insufficient evidence on their impact in melanoma care and the lack of clinically actionable prognostic information. However, GEP testing could still provide more accurate risk prediction when combined with conventional variables and AJCC staging.

“This means that it’s important to understand limitations of testing and to continue communication with our patients,” he concluded.

Reference
Grossman D. Update on gene expression profiling tests. Presented at: AAD Annual Meeting; March 17–21, 2023; New Orleans, LA.