Ten-year outcomes of uveal melanoma based on The Cancer Genome Atlas (TCGA) classification in 1001 cases

Abstract

Purpose: To understand the prognostic value of The Cancer Genome Atlas (TCGA) for uveal melanoma metastasis, using a simplified 4-category classification, based on tumor DNA. Methods: A retrospective cohort study of 1001 eyes with uveal melanoma at a single center, categorized according to TCGA as Group A, B, C, or D (by fine-needle aspiration biopsy for DNA analysis), and treated with standard methods, was studied for melanoma-related metastasis at 5 and 10 years. Results: Of 1001 eyes with uveal melanoma, the TCGA categories included Group A ( n = 486, 49%), B ( n = 141, 14%), C ( n = 260, 26%), and D ( n = 114, 11%). By comparison, increasing category (A vs. B vs. C vs. D) was associated with features of older age at presentation (56.8 vs. 52.8 vs. 61.1 vs. 63.5 years, P < 0.001), less often visual acuity of 20/20–20/50 (80% vs. 67% vs. 70% vs. 65%, P = 0.001), tumor location further from the optic disc ( P < 0.001) and foveola ( P < 0.001), and greater median tumor basal diameter (10.0 vs. 13.0 vs. 14.0 vs. 16.0 mm, P < 0.001) and tumor thickness (3.5 vs. 5.2 vs. 6.0 vs. 7.1 mm, P < 0.001). The Kaplan–Meier (5-year/10-year) rate of metastasis was 4%/6% for Group A, 12%/20% for Group B, 33%/49% for Group C, and 60%/not available for Group D. Conclusion: A simplified 4-category classification of uveal melanoma using TCGA, based on tumor DNA, is highly predictive of risk for metastatic disease.

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

“…UM develops from the uncontrolled proliferation of melanocytes in the uveal tract, which comprises the pigmented tissues in both the anterior (iris) and the posterior (choroid and ciliary body) segments of the eye ( Figure 1 ). The disease is usually unilateral and the majority of UM cases have their epicenter in the choroid (≈90%), while nearly 6% of them are restricted to the ciliary body and 4% to the iris ( Figure 1 ) [ 1 , 3 , 16 ]. The annual incidence in Europe and USA is ≈5 per million population, but worldwide it can range from <1 to >9 per million population per year [ 17 , 18 , 19 , 20 ].…”

“…Local tumour control is achieved in more than 95% of cases, even for large-size tumours [ 1 , 9 ]. Despite the successful local disease control, metastases will develop in nearly 50% of patients during the first 10 years ( Table 1 ) [ 3 , 16 ].…”

“…Uveal melanoma patients with mutations in BAP1 (highlighted in red) have been demonstrated to have the worst outcome, while patients with EIF1AX (highlighted in green) have a better prognosis and patients with SF3B1/SRSF2 (highlighted in orange) have an intermediate prognosis. Diagram generated in line with previous literature [ 1 , 2 , 3 , 9 , 22 , 25 , 26 , 27 , 36 , 37 , 38 , 39 , 40 ] (Diagram created with BioRender.com, accessed on 15 December 2021).…”

“…The new molecular classification is based on the data gathered from the TCGA project, in which a vast array of 80 UM patients had their primary tumour profiled through a comprehensive analysis involving different molecular methodologies ( Figure 3 ) [ 39 , 40 ]. This new classification comprises four main prognostic classes: class A [D3/Disomy 8 (D8)], class B (D3/partial extra 8q), class C (M3/8q gain) and class D (M3/multiple 8q gains), with progressive increased risk of metastases development and, thus, increased risk of poor prognosis, from class A to class D ( Figure 3 ) [ 3 , 36 , 39 , 40 , 73 ]. This new molecular classification has been demonstrated to be superior to the current gold standard AJCC TNM staging in predicting the risk of metastases and death ( Figure 3 ) [ 3 , 36 , 73 , 139 ].…”

“…Uveal melanoma (UM) is the most common primary malignant neoplasia afflicting the eyes of adults [ 1 , 2 ]. Metastases develop in approximately 50% of patients, who then have a shortened life expectancy [ 1 , 2 , 3 ]. UM metastasis can develop up to 30 years after the initial diagnosis and treatment [ 4 ], and once metastases are detected, the median survival time for UM patients is approximately 12 months, especially because therapeutic options for advanced disease are limited and mostly ineffective [ 5 , 6 , 7 ].…”