Castle Biosciences, Inc. announced a new publication demonstrating that the DecisionDx®-Melanoma gene expression profile (GEP) test can identify high-risk patients who are likely to recur or die from melanoma within groups of patients often considered low risk based on traditional staging metrics. Results from this multicenter study of 690 patients demonstrated that the DecisionDx-Melanoma test is an independent predictor of risk for recurrence, metastasis and melanoma-specific death. The study was published in the January 2019 issue of the Journal of the American Academy of Dermatology (JAAD). Patients from three previously published DecisionDx-Melanoma validation studies were combined to enable analysis of test performance in the following three clinically important subgroups that are traditionally considered low risk based on current national melanoma guidelines: (1) patients who had a negative sentinel lymph node (SLN) biopsy; (2) those with American Joint Committee on Cancer (AJCC) Stage I-IIA melanoma; and (3) those with thin (=1 mm) tumors. The DecisionDx-Melanoma test was performed to determine molecular class for each patient, with a Class 1A result indicating the lowest 5-year risk of metastasis and a Class 2B result indicating the highest risk. Study endpoints included recurrence-free survival (RFS; time to local, regional or distant recurrence), distant metastasis-free survival (DMFS; time to any distant metastasis) and melanoma-specific survival (MSS; time to documented death from melanoma). In this population of 690 unique Stage I-III patients with at least 5 years of follow-up or a metastatic event, median age was 59 years and median Breslow thickness was 1.3 mm. 70% of patients had Stage I or II melanoma. Key Study Findings: In the pooled cohort, patients with Class 1A results had significantly higher RFS, DMFS and MSS rates compared to Class 2B (p<0.0001 for all comparisons). 70% of the patients who were SLN negative and experienced metastasis were identified as Class 2 by the DecisionDx-Melanoma test. Similarly, 79% of melanoma-specific deaths among those who were SLN negative were identified as having a Class 2 result. Patients with Stage I-IIA melanoma who received a Class 2B DecisionDx-Melanoma test result had significantly worse RFS, DMFS and MSS rates compared to patients with a Class 1A DecisionDx-Melanoma result (p<0.0001 for all comparisons). Based on Cox multivariate analysis in the Stage I-IIA subgroup that included tumor thickness, ulceration and mitotic rate, DecisionDx-Melanoma test class was found to be the only significant predictor of all three endpoints (RFS, DMFS and MSS; p<0.05 for all). For patients with thin tumors (=1 mm), although most patients were low risk Class 1, 15 patients had the highest risk Class 2B result. Those patients with a Class 2B test result had a significantly reduced RFS of 64.6% compared to those with a Class 1A result (96.8%; p<0.0001). Results of the study extend previous findings of high prognostic accuracy of the DecisionDx-Melanoma GEP test to subgroups of patients at high risk, yet for whom current national melanoma guidelines recommend low intensity follow-up and surveillance. Additionally, the study’s authors suggest that the results could have an important impact on clinical trials evaluating adjuvant treatment of Stage II disease with immunomodulatory or targeted therapies, as the identification of high-risk Stage II patients may guide appropriate patient enrollment in such trials.