Abstract

Adjuvant systemic therapy is used for high-risk patients with resected melanoma, with risk defined by ?Stage IIIA designation (disease in at least the SLN). A 31-gene expression profile (31-GEP) test (DecisionDx-Melanoma, Castle Biosciences, Inc) predicts metastatic risk by categorizing primary tumors as Class 1 (low risk) or Class 2 (high risk). SLNBx and clinical outcome in 206 patients with 31-GEP testing were studied. 157/206 (76%) were Class 1. 4/157 (2.5%) Class 1 patients showed SLNBx+; none experienced recurrence or melanoma specific mortality (MSM). Of 153 Class 1/SLNBx- patients, 2 experienced recurrences: 1 visceral and 1 cutaneous (pT2a and pT2b respectively) and 1 died of disease (DOD). 49/206 (24%) were Class 2. 4/49 (8%) Class 2 patients had SLNBx+ (SLNBx positivity Class 2 vs 1, p=0.07). 1/4 (25%) Class 2/SLNBx+ developed metastasis (4y post excision) and DOD; the other 3 did not recur. 10/45 (22%) Class 2/SLNBx- developed metastases- 6 visceral, 3 cutaneous, and 1 in the draining LN; 3/10 DOD at last follow-up. We performed deeper levels with SOX-10 immunohistochemical stains (IHC, levels 5, 11, 17 and 23) in Class 2/SLNBx- patients (39/45 with available material). 1/39 (2.6%) showed SOX10+ metastatic melanoma (confirmed PRAME+ and HMB-45+, level 23, patient has not had melanoma recurrence). Our data reaffirm the independent roles of SLNBx and GEP testing to predict risk in cutaneous melanoma. Deeper levels and additional IHC in Class 2/SLNBx- patients may only identify a small number of patients with SLNBx+; our data suggest 2-3% may become eligible for adjuvant systemic immunotherapy by resultant upstaging. These results reaffirm distinct risk for hematogenous metastasis in Class 2 patients, independent of SLNBx status, and suggest 31-GEP may be a useful criteria for adjuvant therapy eligibility, regardless of SLNBx status, although further study is needed.

Financial Disclosure:
No current or relevant financial relationships exist.