4, 5, 6 and 7 Currently, there is no effective NVP-AUY922 nmr systemic treatment for metastasis to improve overall survival,8 resulting inevitably in tumor-related death when metastasis occurs, with the minor exceptions of a small proportion of patients who have successful curative surgery of metastasis or patients with spontaneous regression of metastatic disease. Prognostic factors to identify patients with primary uveal melanoma at risk for metastatic disease include clinical (tumor location, tumor size, age), histologic (cell type, vascular pattern, mitotic count, extraocular extension),

and genetic (chromosomal aberrations, expression profiling, gene mutations) parameters, partially included in the American Joint Committee on Cancer classification of uveal melanoma.9,

10 and 11 Over the past few decades, treatment of the primary tumor has changed drastically because several forms of radiotherapy have replaced enucleation as the preferred treatment of the primary AZD5363 cost tumor, depending on size and location of the tumor and patient preference. However, despite the improvements in diagnosis and the development of eye-conserving treatments, none of these treatment methods prevents the development of metastases. The relative 5-year survival rates have not increased over the past decades, fluctuating at approximately 70% to 80%.4, 12, 13 and 14 Only up to 2% of patients have detectable metastasis when their primary Bumetanide uveal melanoma is diagnosed15; most patients have a long disease-free interval before metastasis becomes clinically evident.4 In uveal melanoma, liver metastases are seen most frequently (90% to 95%), and it is often the sole site of metastatic disease. Other common sites of metastases, mostly in the presence of liver metastases, are lungs (25%), bone (15%), skin (10%), and lymph nodes (10%); in contrast to cutaneous melanoma, uveal melanoma infrequently metastasizes to the brain.16 After metastasis develops, overall survival mainly is independent of previously

mentioned prognostic factors if one is identifying patients with primary uveal melanoma at risk for metastatic disease. Presence of symptomatic disease, metastatic extensiveness, and metastatic-free interval may correlate with survival time.17 Nevertheless, median survival is short, typically less than 9 months, with a poor 1-year survival rate (10% to 40%).7, 17, 18 and 19 The small group of patients in whom metastases are confined to extrahepatic locations have a significantly longer median survival, approximately 19 to 28 months.20 and 21 Several locoregional treatment options can be considered in selected patients with metastasis confined to the liver, including surgery, isolated hepatic perfusion, or radiofrequency ablation.