Liver metastasis in uveal melanoma — treatment options and clinical outcome

Abstract

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults with a stable incidence rate between five and seven cases per million in Europe and the United States. Although UM and melanoma from other sites have the same origin, UM has different epidemiological, biological, pathological and clinical features including characteristic metastatic hepatotropism. Despite improvements in the treatment of primary tumours, approximately 50% of patients with UM will develop metastases. In 90% of cases the liver is the first site of metastasis, however the mechanisms underlying this hepatic tropism have not been elucidated. Metastatic disease is associated with a very poor prognosis with a median overall survival of 6 to 12 months. Currently, there is no standard systemic treatment available for metastatic UM and once liver metastases have developed, prognosis is relatively poor. In order to prolong survival, close follow-up in all patients with UM is recommended for early detection and treatment. The treatment of metastatic UM includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, radioembolization, chemoembolization, immunoembolization, isolated and percutaneous liver perfusion as well as thermal ablation represent available treatment options. However, to date a consensus regarding the optimal method of treatment is still lacking and the importance of setting guidelines in the treatment and management of metastatic UM is becoming a priority. Improvement in knowledge and a better insight into tumour biology, immunology and metastatic mechanism may improve current treatment methods and lead to the development of new strategies paving the way for a personalized approach.

Association between <em>IL11RA</em> Overexpression and the Initiation of Melanoma Liver Metastasis

“…The mechanisms of melanoma metastasis have been the subject of extensive studies for decades, as melanoma has one of the highest metastatic potential among human cancers with diverse secondary tumor sites including liver [14,25,26]. However, most of the recent studies are focusing on the most common primary cancers that metastasizes to the liver, including colorectal-and pancreatic cancers, as well as uveal melanoma [15,[27][28][29]. The organotropism of the liver is influenced by different factors such as blood flow pattern, tumor stage and histological subtype of the tumor [17].…”

“…The most common sites of distant metastases in melanoma patients include skin, liver, lung, and brain; however, the initial sites of melanoma cell spread are typically lymph nodes [7,14]. Liver metastases are observed in 10-20% of patients with cutaneous melanoma, which occur relatively late during disease progression with an average 2-4 months survival [14][15][16]. The liver has a rich blood supply and therefore provides fertile "soil" for metastatic spread [17].…”

Choroidal Melanoma: A Mini Review

“…Unfortunately, the survival rates of patients suffering from UM have not improved in the past 30 years, even with the availability of various treatment modalities [ 1 ]. The percentage of patients with hepatic metastasis is approximately 80%, 92%, and only 1% after one year, two years, and over five years, respectively, regardless of the management option [ 67 ].…”

Pharmacological drug screening to inhibit uveal melanoma metastatic cells either via EGF-R, MAPK, mTOR or PI3K

“…Characteristic localizations of tumor spread are, in order of their probability of occurrence, the liver, the lung, the bones, and the skin. The occurrence of liver metastasis is crucial for the further course of disease as it typically results in a median survival of 6-12mo [3] . The development of metastasis located elsewhere offers a longer life expectancy [4] .…”