Uveal Melanoma: Metastases
Although there are effective treatments for primary uveal melanoma, the prognosis for metastatic disease is poor. There is no curative therapy for metastatic uveal melanoma, but options include local interventions such as surgical resection, chemoemboliza
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Lucy T. Xu, Pauline Funchain, Ahmad A. Tarhini, and Arun D. Singh
Introduction In general, the survival of patients with metastatic uveal melanoma is poor. The most common site of metastasis is the liver. Treatment options include systemic therapy including chemotherapy and immunotherapy, as well as local therapy including surgical resection, radioembolization, and intrahepatic chemotherapy. Median overall survival was previously reported to be between 3 and 10 months although more recent studies have shown overall survival closer to 20 months [1–4]. In this chapter, the pathogenesis, clinical features, and treatment of metastatic uveal melanoma are outlined.
These not only determine which patients ultimately develop metastases but also how rapidly metastasis develops following the treatment of the primary uveal melanoma [5]. Gene expression profiling of uveal melanoma is yielding important new insights into the pathogenesis of uveal melanoma, and there is correlation of gene expression pattern (PHLDA1, FZD6, and ENPP2) with cytogenetic changes [6], improving prognostic accuracy [7]. The correlation between the loss of expression of HLA Class I antigens and improved survival indicates that there is an ongoing NK-cellmediated surveillance of uveal melanoma tumor cells in the systemic circulation [8].
Pathogenesis
Clinical Features
Cytogenetic studies have demonstrated that nonrandom alterations of monosomy 3 and additional copies of 8q independently predict worse outcome.
Frequency of Metastasis
L. T. Xu Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA P. Funchain · A. A. Tarhini Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USA A. D. Singh (*) Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA e-mail: [email protected]
Clinically evident metastatic disease at the time of initial presentation is detected in less than 1% of all patients [9]. Nevertheless, long-term follow-up of treated patients reveals metastasis in 31% of cases in 5 years, 45% in 15 years, and almost 50% in 25 years (Fig. 22.1) [10]. These observations suggest that subclinical metastasis is present in such cases at the time of primary treatment. The correlation of primary and metastatic uveal melanoma growth data suggests that metastasis commences when the primary tumor is still small [11]. At the time of diagnosis of the primary uveal melanoma,
© Springer Nature Switzerland AG 2019 B. E. Damato, A. D. Singh (eds.), Clinical Ophthalmic Oncology, https://doi.org/10.1007/978-3-030-17879-6_22
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318 1.0 Proportion who died
Fig. 22.1 Kaplan– Meier estimate of all-cause and melanoma- specific mortality (Adapted from Kujala et al. [10])
L. T. Xu et al.
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Time from enucleation (years) All cause
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Fig. 22.2 Inferred growth of primary (red line) and metastatic uveal melanoma (green line) based on tumor doubling times. It takes 2.2 years after the
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