Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D

Abstract

The Cancer Genome Atlas (TCGA) classification has been validated for uveal melanoma (UM) prognostication. We applied TCGA classification to UM biopsied using fine-needle aspiration biopsy (FNAB) to determine the predictability for metastasis and death. Retrospective cohort study. Patients with UM treated with plaque radiotherapy at Wills Eye Hospital, Philadelphia, Pennsylvania, from October 1, 2008, through December 31, 2018, who completed genetic analysis of chromosomes 3 and 8 after FNAB. Tumors were classified as A, B, C, or D and were compared using the chi-square test, Fisher exact test, analysis of variance, and Kaplan-Meier analysis. Metastasis and death. Six hundred fifty-eight UM patients were categorized accordingly as TCGA class A (n= 342 [52%]), B (n= 91 [14%]), C (n= 118 [18%]), and D (n= 107 [16%]). More advanced tumor classification revealed older mean patient age (56 vs. 53 vs. 60 vs. 63 years, respectively; P < 0.001), worse presenting visual acuity (20/20-20/50: 81% vs. 67% vs. 71% vs. 66%, respectively; P < 0.001), greater distance from the optic disc (3.5vs. 4.9 vs. 5.7 vs. 5.3 mm, respectively; P < 0.001), larger tumor basal diameter (10.3 vs. 12.9 vs. 13.9 vs. 15.3mm, respectively; P < 0.001), and greater tumor thickness (4.3 vs. 6.1 vs. 6.6 vs. 7.5 mm, respectively; P<0.001). After mean follow-up (47.6 vs. 47.6 vs. 42.9 vs. 28.7 months, respectively; P < 0.001), more advanced TCGA class was associated with increased risk of metastasis (3% vs. 10% vs. 25% vs. 41%, respectively; P<0.001) and death (1% vs. 0% vs. 3% vs. 9%, respectively; P < 0.001). Compared with class A, the 5-year hazard ratio for metastasis increased at 4.1 (B vs. A; P= 0.01), 10.1 (C vs. A; P < 0.001), and 30.0 (D vs. A; P< 0.001). The 5-year hazard ratio for death increased at 3.1 (C vs. A; P= 0.11) and 13.7 (D vs. A; P<0.001) with no deaths in class B. Grouping of UM using TCGA classification predicts the risk of melanoma-related metastasis and death.