Uveal melanoma is a rare eye cancer that demands careful attention and specialized treatment approaches. While it affects only about 5 people per million each year, this cancer presents unique challenges because it can spread to other organs even after successful treatment of the tumor in the eye. Understanding treatment options—both standard and experimental—is essential for patients navigating this diagnosis.

When Cancer Hides in Plain Sight: Treating Uveal Melanoma

The treatment of uveal melanoma begins with a primary goal: to eliminate or control the tumor in the eye while preserving vision whenever possible. Unlike many other cancers, uveal melanoma can often be diagnosed without removing tissue from the body, through careful examination by eye specialists using specialized imaging equipment. This means that treatment decisions can frequently be made quickly once the cancer is identified.^[1]

The approach to treatment depends heavily on where the tumor is located within the eye and how large it has grown. Tumors in the iris, the colored part of the eye, tend to grow slowly and rarely spread to other parts of the body. These may require different treatment than tumors in the choroid or ciliary body, which are more likely to spread and require more aggressive management. The stage of the cancer—determined by its size, location, and whether it has spread—guides doctors in selecting the most appropriate treatment strategy.^[2]

Treatment also takes into account individual patient factors such as age, overall health, vision in both eyes, and personal preferences about quality of life. Some patients prioritize keeping their eye and preserving whatever vision remains, even if it means undergoing more complex treatments. Others may choose simpler approaches if the affected eye has already lost useful vision. Medical teams work closely with patients to balance these considerations against the need to control the cancer effectively.^[4]

Standard Treatment Approaches That Preserve Eyes and Lives

The most widely used treatment for uveal melanoma is radiation therapy, which delivers focused energy to destroy cancer cells while attempting to spare surrounding healthy tissue. Two main types of radiation are employed, each with specific advantages depending on the tumor’s characteristics.^[6]

Plaque brachytherapy involves surgically placing a small radioactive disc, or plaque, on the outside of the eye directly over the tumor location. This plaque, which may contain radioactive iodine-125, ruthenium-106, palladium-103, or cobalt-60, remains in place for several days while it delivers a concentrated dose of radiation to the tumor. The plaque is then removed in a second brief surgical procedure. This approach allows radiation to target the tumor precisely while minimizing exposure to other parts of the body. Patients typically remain in the hospital during the few days the plaque is in place, and may need to limit contact with others due to the radioactive material.^[2][6]

Proton beam therapy represents another form of radiation treatment that uses protons—positively charged particles—rather than X-rays. Proton beams can be directed with extreme precision, stopping at the tumor site and releasing their energy without traveling through to damage structures behind the eye. This treatment is delivered over multiple sessions, typically four to five visits over about a week. Patients must remain very still during treatment, and tiny metal clips may be placed on the eye beforehand to help guide the radiation beam accurately.^[2][6]

Both radiation approaches aim to preserve the eye and whatever vision remains possible. However, radiation can cause side effects that develop months or even years after treatment. These may include radiation retinopathy (damage to the blood vessels in the retina), cataracts, dry eye, glaucoma, or progressive vision loss. The risk and severity of side effects depend on the tumor’s size and location, with tumors near critical structures like the optic nerve or macula carrying higher risk of vision-threatening complications. Despite these potential problems, radiation successfully controls the tumor in most patients, making it the preferred first-line treatment for medium-sized melanomas.^[15]

For very small melanomas or suspicious lesions that might be benign nevi (eye freckles), doctors may recommend active monitoring rather than immediate treatment. This involves regular eye examinations with photography and ultrasound every few months to detect any growth. If the lesion begins to enlarge or show other concerning changes, treatment can be started at that point. This watchful waiting approach spares patients the side effects of treatment when the diagnosis is uncertain, but requires commitment to regular follow-up appointments.^[14][17]

Other specialized techniques may be used for specific situations. Transpupillary thermotherapy uses laser heat to destroy small tumors, sometimes in combination with radiation. Photocoagulation employs intense laser light to seal off blood vessels feeding the tumor. Local resection surgically removes the tumor along with a margin of healthy tissue, preserving the eye but requiring complex microsurgical techniques. These approaches are generally reserved for selected cases where standard radiation may not be ideal.^[6]

Enucleation—surgical removal of the entire eye—remains an important treatment option for large tumors where radiation would likely fail or cause severe complications, or when the eye has already lost useful vision. While losing an eye is emotionally difficult, modern prosthetic eyes provide excellent cosmetic results. Enucleation also eliminates any chance of local tumor regrowth, which can occur rarely after radiation. After healing, patients are fitted with an artificial eye that matches their remaining eye and moves naturally with the eye muscles.^[2][4]

The duration of treatment varies considerably. Plaque brachytherapy requires hospitalization for several days, while proton beam therapy involves daily treatments for about a week. After these initial treatments, patients enter a long-term monitoring phase with eye examinations every three to six months initially, then annually once the tumor appears stable. These follow-up visits check for tumor recurrence and monitor for treatment side effects that may require additional interventions like cataract surgery or glaucoma treatment.^[15]

Investigating New Frontiers: Treatment in Clinical Trials

Despite successful control of the eye tumor in most patients, the persistent risk of metastatic disease has driven intensive research into new treatment approaches. Clinical trials are testing innovative therapies aimed at either improving local tumor control or, more importantly, preventing or treating cancer spread to other organs.^[6]

Recent advances in understanding the genetics of uveal melanoma have opened doors to targeted treatments. Scientists have discovered that nearly all uveal melanomas have mutations in specific genes called GNAQ or GNA11, which provide instructions for proteins involved in cell signaling. Tumors can now be classified based on their genetic profile into Class I (low risk of spreading) and Class II (high risk of spreading). This classification, obtained through biopsy of the tumor, helps identify which patients might benefit most from aggressive monitoring or experimental therapies aimed at preventing metastasis.^[2][11]

Immunotherapy represents one of the most promising areas of clinical trial research for metastatic uveal melanoma. These treatments work by helping the patient’s own immune system recognize and attack cancer cells. However, uveal melanoma has proven more resistant to immunotherapy than skin melanoma, which responds well to these agents. Researchers are testing various immunotherapy drugs and combinations to overcome this resistance. Checkpoint inhibitors, which block proteins that prevent immune cells from attacking cancer, are being studied in multiple Phase II and Phase III trials for patients whose cancer has spread to the liver or other organs.^[2]

Trials are also investigating drugs that target the specific molecular pathways disrupted by GNAQ and GNA11 mutations. One promising agent that has shown encouraging results in early trials is a drug targeting protein kinase C, an enzyme activated by these mutations. In Phase I and II studies, some patients with metastatic uveal melanoma experienced slowing of tumor growth or temporary shrinkage when treated with these targeted molecules. While these early results are encouraging, larger Phase III trials are needed to determine whether these drugs truly extend survival.^[12]

Another research focus involves liver-directed therapies for patients who develop metastases, since the liver is the most common site of spread. Clinical trials are testing techniques like hepatic artery infusion, where chemotherapy drugs are delivered directly into the blood vessels feeding liver tumors, providing higher drug concentrations to the cancer while limiting side effects on the rest of the body. Other approaches being studied include percutaneous hepatic perfusion, a procedure that temporarily isolates the liver’s blood supply to deliver very high doses of chemotherapy to liver metastases.^[8]

Some trials are exploring whether treating patients with targeted therapy or immunotherapy immediately after diagnosis of the primary eye tumor—before any evidence of metastasis—might prevent cancer cells from establishing themselves in distant organs. These adjuvant trials are particularly important for patients whose tumors show high-risk genetic features, as they are most likely to develop metastatic disease. The challenge is determining which treatments are effective enough to justify their side effects in patients who may never develop metastasis.^[11]

Tumor biopsy has become increasingly important in uveal melanoma, not just for diagnosis but also for accessing clinical trials. Many experimental treatments are only available to patients whose tumors have specific genetic characteristics. A small sample of tumor tissue, obtained either during radiation plaque placement or through a fine needle inserted into the eye, can be analyzed for genetic mutations. This procedure carries minimal risk when performed by experienced specialists and provides crucial information for treatment planning and trial eligibility.^[11]

Clinical trials for uveal melanoma are conducted at specialized centers in the United States, Europe, and other regions. Patients interested in trial participation typically need a referral to one of these centers, which have expertise in ocular oncology. Many trials have specific eligibility requirements based on tumor size, location, genetic characteristics, and whether metastasis has occurred. Trial phases indicate the stage of testing: Phase I studies primarily evaluate safety and appropriate dosing in small numbers of patients, Phase II trials assess whether the treatment shows evidence of effectiveness, and Phase III trials compare new treatments against current standard approaches in larger patient groups.^[16]

Most Common Treatment Methods

• Radiation Therapy
  • Plaque brachytherapy using radioactive iodine-125, ruthenium-106, palladium-103, or cobalt-60 plaques placed directly on the eye over the tumor location
  • Proton beam therapy delivering precisely targeted radiation using charged particles
  • Stereotactic radiosurgery using gamma knife, cyber knife, or linear accelerators to deliver focused radiation
  • Helium ion therapy, similar to proton beam but using heavier particles
• Surgical Approaches
  • Enucleation (removal of the affected eye) for large tumors or when vision is already lost
  • Local resection surgically removing the tumor while preserving the eye structure
  • Tumor biopsy to obtain tissue samples for genetic analysis and treatment planning
• Laser Treatments
  • Transpupillary thermotherapy using laser heat to destroy small tumors
  • Photocoagulation employing intense laser light to cut off tumor blood supply
  • Photodynamic therapy combining light-sensitive drugs with laser activation
• Active Monitoring
  • Regular observation with photography and ultrasound for small or suspicious lesions
  • Treatment initiated only if growth or concerning changes are detected
• Experimental Treatments in Clinical Trials
  • Immunotherapy drugs including checkpoint inhibitors to enhance immune system recognition of cancer cells
  • Targeted therapies blocking protein kinase C and other enzymes activated by tumor mutations
  • Liver-directed treatments including hepatic artery infusion and percutaneous hepatic perfusion for metastatic disease
  • Adjuvant therapies given after primary treatment to prevent metastasis in high-risk patients