A Prognostic Indicator for Melanoma Metastasis

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Gerami et al (Clin Cancer Res. 2015;21:175-183) discussed the development and use of a genetic signature to predict the likelihood of metastasis from cutaneous melanoma. A genetic signature comprised of 28 prognostic genetic targets and 3 control genes was developed from the expression data available and reverse transcriptase–polymerase chain reaction analysis of more than 260 primary cutaneous melanoma cases was performed. Genetic expression data from public databases were used to identify genes that were similarly upregulated or downregulated in metastatic disease. The analysis of cutaneous melanoma and uveal melanoma tumors led to the selection of 54 gene targets that had different expression profiles for primary tumors compared with metastatic tumors. Of the 54 targets of interest, 20 were selected for further reverse transcriptase–polymerase chain reaction analysis based on genetic loci. Additionally, analysis of metastatic and nonmetastatic primary cutaneous melanoma tumors using a profile assay for uveal melanoma led to the selection of 5 additional gene targets. The sample set of cases included 107 stage I and stage II primary melanomas. Twenty cases had metastatic disease and 5 cases had regional recurrence.

Prediction of metastatic risk for this test was classified either as class 1 (low risk) or class 2 (high risk). In the development cohort, 43 of 107 cases were predicted to be class 2. All cases with documented metastatic progression were called class 2 (100% sensitivity), whereas 64 of 82 nonmetastatic cases were called class 1 (78% specificity; accuracy determined by the area under the receiver operating characteristic curve, 0.93). Kaplan-Meier survival analysis revealed that disease-free survival for the predicted classes was significantly different (P<.0001). Also, the median time to metastasis for class 2 cases was 2.5 years, whereas the median time for class 1 cases was not reached. Five-year disease-free survival was 100% for class 1 cases compared with 38% for class 2 cases.

What’s the issue?

Stage I cutaneous melanoma tumors have a 5-year overall survival rate of 91% to 97%. Although the majority of clinical stage I patients will be disease free at 5 years, some stage I patients will develop advanced disease. Furthermore, prognosis for clinical stage II and stage III cases by the TNM staging system is highly variable, as evidenced by a 5-year survival rate of 53% to 82% for stage II patients and a 5-year survival rate of 22% to 68% for stage III patients. However, up to 20% of stage I and stage II patients will die from the disease within 4 years of the initial diagnosis. This statistic can be difficult for patients, as it can be unclear which stage I and stage II patients are more at risk.

This test had a limited number of samples that were used to create this predictive tool. Would patients with stage I and stage II disease deemed to be high risk by this test benefit from adjuvant therapy and/or enhanced imaging protocols to allow for early detection of metastasis? Will you be recommending this test to your melanoma patients?

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