Approximately 400 Italians are diagnosed each year with uveal melanoma, a rare eye cancer. Early detection through annual eye exams is crucial, and a range of treatments are available with a growing focus on preserving vision.
Around 400 Italians each year receive a diagnosis of uveal melanoma, the most common type of malignant eye tumor in adults. This disease often doesn’t present with clear symptoms, but there are some warning signs that shouldn’t be ignored. Early diagnosis is key to preserving the affected eye (uveal melanoma develops inside the eyeball) and, importantly, reducing the risk of metastasis.
What are the possible warning signs?
“Uveal melanoma typically peaks in incidence between the ages of 55 and 65, and is relatively rare before age 20 or after 75,” explains Paolo Nucci, Professor of Ophthalmology at the University of Milan. In some cases, the tumor is visible as a dark spot or a non-pigmented lesion rich in blood vessels on the surface of the eye or iris. More often, but, it develops inside the eye and causes non-specific symptoms, such as a decrease in vision or the presence of flashes of light. In about a third of cases, however, the patient is completely asymptomatic and the tumor is discovered accidentally during a routine eye exam. This represents why it’s important not to neglect regular checkups.” Early detection is vital for effective treatment and preserving vision in these cases.
What treatment options are available?
“The treatment of choice is radiotherapy, using brachytherapy or external beam radiotherapy, indicated based on the size of the tumor, its location, and the potential vision of the affected eye,” explains Fabrizio D’Ancona, an ophthalmologist specializing in oncology at Royal Liverpool University Hospital in the UK.
Brachytherapy involves surgically placing a metal plaque on the surface of the eye corresponding to the tumor, containing radioactive iodine or ruthenium, and leaving it in place for the number of hours necessary to irradiate the entire tumor volume. Proton beam radiotherapy allows irradiation with a very powerful and precise beam of any volume and is considered the best standard for the treatment of uveal melanomas close to critical structures such as the optic nerve or for those of large size. It can also be used to irradiate the iris, the surface of the eye, and the eyelids.
Are there new forms of radiotherapy?
“Until recently, the lack of protons in Italy forced many patients to seek medical care abroad, especially in Switzerland or France, to receive the necessary treatment. Now, however, the CNAO in Pavia has develop into the national reference center for the treatment of uveal melanoma with proton therapy. Among the available options is also stereotactic radiotherapy with CyberKnife, a non-invasive method performed in highly specialized centers,” adds Marco Pellegrini, a physician in Ophthalmology at Luigi Sacco Hospital in Milan. “In recent years, scientific evidence supporting its effectiveness has gradually consolidated, offering local control rates comparable to other radiotherapy techniques. It now represents a valid alternative in selected patients and Milan is among the European centers with the most clinical experience and treated cases.”
How high is the risk of metastasis?
The various radiotherapy techniques guarantee high rates of local control (90–95%), allowing for the preservation of the eyeball in most cases. However, radiation toxicity to critical ocular structures, particularly the macula and optic nerve, can lead to a significant impairment of visual function over time. It has been widely demonstrated, however, that eye therapy does not affect patient survival. Despite excellent local control, the natural history is dominated by the risk of metastatic disease, which affects up to 50% of patients. “When they occur, metastases affect the liver in about 90% of cases and have a poor prognosis, with a median survival often in the order of 12–16 months,” explains D’Ancona. “This is why new therapeutic strategies are being studied to both preserve vision and limit the risk of metastasis and patient death.”
How does the new experimental drug work?
This is where a new drug (belzupacap sarotalocan) comes into play, now in the most advanced stage of experimentation, phase three, the last before the approval and actual marketing of a medicine. “The CoMpass study recruits patients worldwide and involves four Centers in Italy (Careggi in Florence, National Cancer Institute and Luigi Sacco Hospital in Milan, Gemelli Polyclinic in Rome),” says Pellegrini. “The goal is to evaluate the safety and efficacy of belzupacap sarotalocan as a first-line therapy in patients with indeterminate lesions (potential melanoma, but without certainty/evidence of growth) or with small choroidal melanomas (basal diameter less than 10 mm, and thickness less than 2.5 mm) with documented growth in the last two years. The trial is expected to be completed in 2027 with the first results expected in 2028.” Belzupacap sarotalocan is an innovative experimental drug, a virus-like drug conjugate, a new class of drugs that combines targeted therapy with an immunological action. “The drug is injected into the eye and selectively binds to tumor cells of the melanoma,” continues D’Ancona. “Once activated by near-infrared laser therapy, it generates the selective death of tumor cells that have bound to it, sparing the surrounding tissues and confining the damage to the tumor. The results at the end of the phase (presented in 2024) were promising, showing a tumor control rate of 80% in patients, with a high rate of preservation of visual acuity (observed in 90% of patients), better than what we obtain now with radiotherapy, and minimal side effects.”
When should treatment begin?
It’s not just the best results obtained, however, that give specialists and patients hope, but a real change of perspective. Currently, this tumor is treated only when it becomes large and dangerous, but the goal is to intercept it early with intelligent, targeted therapies aimed at saving vision. Today, oncologists limit themselves to observing indeterminate lesions and small melanomas until there is evidence of growth and therefore malignancy. “Because treatment (radiotherapy) often has important implications for the patient’s quality of life by reducing their visual ability, we wait as long as possible,” experts explain. However, growth means already biological instability and therefore metastatic risk: uveal melanoma can metastasize even when it is small. The key idea behind this new drug is to anticipate treatment with two possible benefits: first, to better preserve vision for the patient, preventing the tumor lesion from growing towards noble areas of the retina, but also thanks to a lower leverage of radiotherapy and therefore the visual complications related to it. Second, to reduce the danger of metastasis.” In reality, the CoMpass study is designed primarily on local control and preservation of visual capacity, but if it were demonstrated that early treatment also reduces metastatic dissemination, then the impact would be enormous. Currently, there are no approved therapies (in Italy, or in Europe or the US) for early-stage uveal melanoma that preserve vision.
