Uveal melanoma: natural history and treatment options for metastatic disease.

In order to evaluate the natural history, prognostic parameters and treatment modalities for metastatic uveal melanoma, a review of the clinical data from the current literature was performed based on a Medline database search. Uveal melanoma represents approximately 5% of all melanomas. It is a distinct clinico-pathological entity, differing in many aspects from cutaneous melanoma. The clinical course is unpredictable and metastatic disease can develop very late after a long disease-free interval. Uveal melanoma metastasizes haematogenously, predominantly to the liver. The most Important prognostic parameters for primary uveal melanoma are tumour diameter, the patient's age and gender, histological features and tumour location. Systemic chemotherapy that is effective in cutaneous melanoma has failed to show activity in uveal melanoma. So far only the BOLD chemotherapy regimen (dacarbazine, lomustine, vincristine and bleomycin) combined with interferon-alpha has been shown to produce an objective tumour response in approximately 20% of previously untreated patients. For metastatic disease localized to the liver, intra-arterial application of fotemustine or carboplatin or chemoembolization with cisplatin have shown useful activity, resulting in a response in up to 40% of patients. Selected patients may benefit from palliative surgery. Immunotherapy with interleukin-2 or interferon-alpha has not shown consistent activity in metastatic uveal melanoma. In conclusion, patients with uveal melanoma metastatic to the liver should undergo one of the local treatment options. Carefully selected patients with extrahepatic disease or patients failing local treatment may benefit from systemic therapy using the BOLD regimen combined with interferon.