Uveal melanoma (UM) is a rare cancer originating in the pigment cells of the eye, specifically within the uvea (iris, ciliary body, and choroid). Although it is the most common primary intraocular cancer in adults, its incidence is low, affecting approximately five people per million annually. The patient’s prognosis depends heavily on whether the cancer remains localized or spreads to distant organs. While the primary goal of management is eliminating the tumor in the eye, long-term survival is determined by the risk of subsequent systemic spread.
Understanding Uveal Melanoma Survival Statistics
Survival outlook for uveal melanoma patients is often described using relative survival rates, which compare the survival of individuals with UM to that of the general population. For localized disease, the five-year relative survival rate is around 82.8%, indicating a relatively favorable short-term prognosis. However, the long-term outcome is significantly influenced by the high rate of metastasis that can occur many years after the initial diagnosis. Since roughly half of all patients eventually develop metastatic disease, the overall relative survival rate drops to about 79% at five years and 69% at ten years. When the cancer spreads, the prognosis changes dramatically; metastatic uveal melanoma is highly challenging to treat, and survival following the diagnosis of systemic spread averages less than one year, with some studies reporting a median survival of only four to six months.
Key Factors Influencing Prognosis
Survival statistics are heavily modified by specific biological and clinical characteristics of the tumor. Tumor size is a major determinant; smaller tumors carry a much better prognosis than larger ones. For example, the five-year survival rate after treatment can be 84% for small tumors but drops to 47% for large tumors. The anatomical location also affects the risk profile, as tumors involving the ciliary body carry a higher risk of metastasis compared to those confined to the choroid. The microscopic makeup of the tumor provides important clues about its aggressiveness. Tumors composed primarily of epithelioid cells are associated with a greater risk of metastasis and a poorer overall prognosis than those made up of spindle cells.
Genetic profiling is now standard practice for predicting metastatic risk, focusing on chromosomal abnormalities, particularly chromosome 3 status. Tumors exhibiting Monosomy 3 (loss of one copy of chromosome 3) are classified as high-risk and are far more likely to metastasize. Conversely, tumors with Disomy 3 (two copies of chromosome 3) are associated with a much lower risk of systemic spread. Patients with Monosomy 3 show an average survival of about five months after metastasis detection, while those with Disomy 3 can have an average survival extending to 69 months.
Primary Treatment Modalities
Initial treatment focuses on achieving local control by eradicating the primary tumor. The choice of modality depends on the tumor’s size, location, and the patient’s visual prognosis. These local treatments are highly effective at eliminating the primary tumor but do not prevent the later development of distant metastasis.
Radiation therapy is the most common approach for small and medium-sized tumors. Plaque brachytherapy involves surgically placing a small, radioactive disc (often containing Iodine-125) directly onto the outer wall of the eye to deliver localized radiation. Proton beam radiation is another option, using an external, focused beam of charged particles to deliver radiation while minimizing damage to surrounding healthy tissue.
Surgery (enucleation, or removal of the entire eye) is typically reserved for very large tumors or when radiation therapy cannot preserve useful vision. Long-term survival remains tied to whether microscopic cancer cells had already escaped the eye before treatment began.
Addressing the Risk of Metastasis
The greatest threat to long-term survival is systemic spread, which occurs through the bloodstream. The liver is the most common site, involved in approximately 90% of metastatic cases. Metastasis often develops years, sometimes decades, after successful treatment of the primary tumor.
Because of this delayed and aggressive pattern of spread, regular, lifelong surveillance is necessary, especially for high-risk patients identified through genetic testing. Surveillance protocols typically involve periodic liver imaging, such as ultrasound or magnetic resonance imaging (MRI), often performed every six months. This monitoring aims to detect metastatic lesions when they are small and asymptomatic, allowing for earlier intervention.
When metastasis is detected, the focus shifts to systemic treatments. Metastatic uveal melanoma is historically resistant to many standard therapies, showing limited response to common immune checkpoint inhibitors. However, newer therapies, such as the bispecific T-cell engager tebentafusp, have demonstrated an improvement in overall survival for some patients with advanced disease. Locoregional therapies, including chemoembolization and radioembolization, are also used to focus treatment directly on liver tumors, aiming to control disease progression and extend life.