Uveal melanoma is a rare form of cancer originating in the eye, specifically within the uvea, which is the middle layer of the eye containing blood vessels and pigment cells. Although uncommon, it is the most frequent primary malignant eye tumor in Caucasian adults. The term “metastasis” refers to the spread of cancer cells from their initial site to other parts of the body, and about half of uveal melanoma patients may develop metastatic disease.
How Uveal Melanoma Spreads
Uveal melanoma cells can detach from the primary tumor in the eye and travel through the bloodstream to distant organs. Uveal melanoma primarily spreads via the circulatory system. These circulating tumor cells can be present even before clinical signs of metastatic disease appear.
The liver is the most frequent site for uveal melanoma to metastasize, affecting 90% to 95% of patients who develop metastatic disease. This high propensity for liver involvement is attributed to the liver’s extensive blood supply and a potential symbiosis between uveal melanoma cells and the hepatic microenvironment. Other common sites of spread include the lungs (in about 24% of cases), bones (in about 16% of cases), and skin (in about 11% of cases). While less common, spread to lymph nodes or the brain can also occur.
Identifying Signs and Symptoms
When uveal melanoma metastasizes, the signs and symptoms depend on the organs affected. Liver involvement can lead to symptoms such as abdominal pain, an enlarged liver, or loss of appetite. Jaundice, a yellowing of the skin or eyes, can also occur due to liver dysfunction. These symptoms may appear an average of 27 months after the initial uveal melanoma diagnosis.
If the cancer spreads to the lungs, individuals might experience difficulty breathing or a persistent cough. Metastasis to the bones can cause bone pain or an increased risk of bone fractures. Skin metastases may present as hardened lumps or nodules under the skin. These symptoms can be non-specific and may sometimes only appear in advanced stages of the disease.
Detecting Metastatic Uveal Melanoma
Detecting metastatic uveal melanoma involves various diagnostic procedures. Liver function tests, which measure enzymes and proteins in the blood, are commonly used to assess liver health, as liver dysfunction can indicate metastasis. However, it is possible for patients to have liver metastases even with normal liver enzyme levels.
Imaging scans are regularly employed to visualize potential metastatic lesions. Magnetic Resonance Imaging (MRI) of the liver is highly effective, detecting metastatic disease in a high percentage of patients before symptoms emerge. Computed Tomography (CT) scans of the chest, abdomen, and pelvis are also used to identify cancer spread in these areas. Positron Emission Tomography (PET) scans can provide whole-body imaging to detect metastatic sites. If suspicious lesions are found, a biopsy, which involves removing a small tissue sample for laboratory analysis, can confirm the diagnosis and provide information about the cancer’s characteristics.
Treatment Options
Treatment for metastatic uveal melanoma focuses on controlling the disease and improving quality of life. Systemic therapies, which treat the entire body, include targeted therapies and immunotherapy. Tebentafusp (Kimmtrak) is a notable targeted therapy, approved for patients whose cells express the HLA-A02:01 protein. This bispecific fusion protein works by bringing immune cells close to cancer cells to facilitate an attack, and it has shown improved overall survival in clinical trials compared to other standard treatments.
Immunotherapy drugs, such as immune checkpoint inhibitors like ipilimumab and pembrolizumab, aim to boost the body’s immune response against cancer. While these have shown significant success in other melanoma types, their efficacy in metastatic uveal melanoma has been more limited, with modest response rates. Chemotherapy, though historically not very effective for metastatic uveal melanoma, may also be considered.
Locoregional therapies target specific metastatic sites, especially the liver. These therapies can include hepatic artery chemoembolization, where chemotherapy drugs are delivered directly to the liver through its main artery, or radioembolization, which uses radioactive beads. Surgical resection, or the removal of liver metastases, may be an option for selected patients. Radiation therapy can also be used to target specific tumors. Clinical trials continue to investigate new and emerging treatments, offering additional options for patients with metastatic uveal melanoma, particularly for those who do not express the HLA-A02:01 protein.