Gene Expression Profiling in Uveal Melanoma: Five-Year Prospective Outcomes and Meta-Analysis

Abstract

Introduction: The prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) predicts metastatic risk based on primary tumor biology. Here we report outcomes from a prospective registry of 15-GEP-tested patients, and a meta-analysis with published cohorts. Objectives: Management and 5-year clinical outcomes following 15-GEP testing were evaluated. Methods: Eighty-nine patients with 15-GEP results were prospectively enrolled at four centers. Physician-recommended management plans were collected, and clinical outcomes tracked every 6 months. Results: Eighty percent of Class 1 (low-risk) patients underwent lowintensity management; all Class 2 (high-risk) patients underwent high-intensity management (p < 0.0001). Median follow-up for event-free patients was 4.9 years. Five Class 1 (10%) and 23 Class 2 (58%) tumors metastasized (p < 0.0001). Five-year Class 1 and 2 metastasis-free survival rates were 90% (81-100%) and 41% (27-62%; p < 0.0001), and melanoma-specific survival rates were 94% (87-100%) and 63% (49-82%; p = 0.0007). Class 2 was the only independent predictor of metastasis and was associated with increased risk for metastasis and mortality by meta-analysis. Conclusions: UM patient management is guided by 15-GEP testing. Class 2 patients were managed more intensely, in accordance with an observed metastatic rate of > 50%; Class 1 patients were safely spared intensive surveillance, resulting in appropriate utilization of healthcare resources.

Small Choroidal Melanoma: Correlation of Growth Rate with Pathology

“…Diagnostic cytology showing spindle or mixed-type melanoma cells [1] was included in the pathology group as previous reported studies have shown 100% correlation between cytologic and histopathologic diagnosis of choroidal melanoma in enucleated eyes [1, 22]. Also known from previous reported studies is a prognostic 15-gene expression profile (15-GEP) test which predicts 5-year metastatic risk with class 1A, 1B, and 2 results indicating low-, intermediate-, and high-risk groups, respectively [23-25]. The second group included patients with documented growth prior to treatment (growth-confirmed group), and the third group comprised patients wherein both pathologic confirmation and documented growth were available (combined group).…”

Genetic Landscape and Emerging Therapies in Uveal Melanoma

“…More recently, the 5-year outcome results of a prospective study of 89 patients enrolled at four centers showed 5-year Class 1 and 2 metastasis rates to be 10% and 58%, respectively. Metastasis-free survival rates for Class 1 and 2 tumors were 90% and 41%, respectively [ 54 ].…”

“…Several studies have shown that physicians utilizing cytogenetic and molecular testing for their UM patients are following surveillance plan recommendations aligned with metastatic risk [ 54 , 108 , 109 , 110 , 111 ]. A multicenter prospective study of 138 UM patients who were tested with the commercially available Castle Biosciences DecisionDx-UM Gene Expression Profile found that Class 2 patients had significantly higher surveillance intensity [ 110 ].…”

Analytical Validation and Performance of a 7-gene Next-generation Sequencing Panel in Uveal Melanoma

“…Uveal melanoma (UM) is a rare but deadly intraocular cancer, with up to 50% of patients ultimately developing distant metastatic disease [1]. A 15-gene expression profiling (GEP) test commercially available as DecisionDx-UM (Castle Biosciences, Inc) is routinely used for prognostication of metastatic risk in UM patients and is considered standard of care in many ocular oncology centers across North America [2][3][4]. Testing is typically performed on fine needle aspirate biopsy (FNAB) taken from the primary tumor at the time of surgery for radiotherapy, or on formalin fixed paraffin embedded (FFPE) tissue taken from the primary tumor at the time of enucleation (eye removal).…”