Identification of high-risk cutaneous melanoma tumors is improved when combining the online American Joint Committee on Cancer Individualized Melanoma Patient Outcome Prediction Tool with a 31-gene expression profile-based classification.

Background: A significant proportion of patients with American Joint Committee on Cancer (AJCC)-defined early-stage cutaneous melanoma have disease recurrence and die. A 31-gene expression profile (GEP) that accurately assesses metastatic risk associated with primary cutaneous melanomas has been described.

Objective: We sought to compare accuracy of the GEP in combination with risk determined using the web-based AJCC Individualized Melanoma Patient Outcome Prediction Tool.

Methods: GEP results from 205 stage I/II cutaneous melanomas with sufficient clinical data for prognostication using the AJCC tool were classified as low (class 1) or high (class 2) risk. Two 5-year overall survival cutoffs (AJCC 79% and 68%), reflecting survival for patients with stage IIA or IIB disease, respectively, were assigned for binary AJCC risk.

Results: Cox univariate analysis revealed significant risk classification of distant metastasis-free and overall survival (hazard ratio range 3.2-9.4, P < .001) for both tools. In all, 43 (21%) cases had discordant GEP and AJCC classification (using 79% cutoff). Eleven of 13 (85%) deaths in that group were predicted as high risk by GEP but low risk by AJCC.

Limitations: Specimens reflect tertiary care center referrals; more effective therapies have been approved for clinical use after accrual.

Conclusions: The GEP provides valuable prognostic information and improves identification of high-risk melanomas when used together with the AJCC online prediction tool.