Lifetime risk of invasive melanoma continues to increase, with an estimated risk of 1 in 43 as of 2025. With rates of melanoma on the rise, diagnostic and prognostic tools are becoming more important than ever. In this seminar-in-depth, Laura Ferris, MD, PhD, and Darrell Rigel, MD, MS, review the latest data on diagnostic and prognostic tools for both invasive melanoma and high-risk squamous cell carcinoma (SCC) and discuss strategies on how to incorporate these tools into clinical practice. Beginning with invasive melanoma, Drs Ferris and Rigel reminded the audience of current National Comprehensive Cancer Network (NCCN) guidelines for the staging of invasive melanoma and discussed limitations of the American Joint Committee on Cancer (AJCC) staging. While 92% of all invasive melanomas are stage I-II at diagnosis and are considered to have a low risk of recurrence, 60% of all melanoma deaths were stage I-II at diagnosis, indicating a gap in prognostication with AJCC staging.

The 31-gene expression profiling (GEP) test for invasive melanoma uses a validated algorithm to more accurately predict the individual risk of recurrence and metastasis and is supported by evidence from 40+ peer reviewed publications including over 10,000 patients. A recent review found that 51% of patients who underwent 31-GEP testing had a change in management based on their test result. The 31-GEP test has also been shown to reduce unnecessary sentinal lymph node biopsies, with one prospective study showing the 31-GEP test could reduce biopsies by 25%. The risk stratification for patients was recently validated using the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the SEER database with a Class 1A, 1B, and 2A 31-GEP result had increased melanoma-specific survival and overall survival compared to Class 2B patients. Most impressively, a prospective study comparing patients with invasive melanoma in the SEER database who received a 31-GEP test to those who did not, patients who were tested were found to have a 27% benefit in 3-year melanoma-specific survival and a 21% benefit in 3-year overall survival.

To conclude this seminar-in-depth, Drs Ferris and Rigel reviewed the 40-GEP test for evaluating metastatic risk in patients with high-risk cutaneous SCC. The 40-GEP test stratifies risk for metastasis across three biologic risk classes (Class 1, 2A, and 2B) and has been confirmed by two independent studies. A prospective study of the benefit of adjuvant radiation therapy (ART) in tested patients showed that only Class 2B patients saw a reduction in rates of metastasis with ART, indicating that 40-GEP results can help guide clinical decisions on a patient’s need for it. When combined with current staging systems such as the Brigham and Women’s Hospital (BWH), the 40-GEP test increased the likelihood of predictive accuracy of metastatic risk of high-risk SCC by 72%. Audience members left this seminar-in-depth with confidence in these two important clinical tools for melanoma and cutaneous SCC prognostication.