My wife and I recently attended a wedding and ended up sitting next to my good friend Earl, an ophthalmologist, who said he reads my column regularly. (To be honest, I am not sure I totally believed him.) Anyway, he asked when I would do a topic related to eyes, so Earl, this one’s for you.
We recently discussed the topic of melanoma, cancers arising from melanocytes. These typically occur in the skin but may occur elsewhere in the body as well, and one of those sites is the uvea of the eye. The uvea is the middle part of the eye that lies between the white part of the eye (the sclera) and the retina, the back of the eye which is light sensitive. Melanocytes typically occur in the uvea and thus there is the possibility for malignancies of these cells, or uveal melanomas, to occur in this region.
Uveal melanoma, though rare, is the most common type of eye cancer. Its incidence rate in the U.S. is about five cases per million annually; there are about 2,500 cases each year in the U.S. They occur about equally in males and females. And in contrast to cutaneous melanomas, which are very rare in those of African descent, uveal melanomas do not seem to vary by race or ethnicity. Furthermore, in contrast to cutaneous melanoma, they are not clearly a function of solar or ultraviolet radiation exposure. The studies on this issue have been conflicting. A meta-analysis published in 2005 found an association of 1.37 with chronic sun exposure, but the result was not statistically significant. Likewise, the latitude of birth was also not significantly associated with risk of uveal melanoma. In contrast, being a welder was found to be a significant risk factor based on five studies with a risk ratio of 2.05 (95% confidence interval 1.20-3.51).
About 50% are of low metastatic risk while 50% are of high metastatic risk. When it metastasizes, the five-year survival is about 15%. The metastatic spread is primarily to the liver.
For those diagnosed with localized disease, poor prognostic factors include increased patient age, increased diameter of the tumor, involvement of the ciliary body (as opposed to the iris), extension of the tumor beyond the sclera, and epithelioid cell type. There is a TNM staging system (tumor, node, metastasis) for this tumor as for other solid tumors, but let us not go there—it is enough to simply rely on the size of the tumor.
For very small tumors, because these tumors may often be indolent in behavior, sometimes monitoring and observation will suffice as adequate management. If that is not adequate or if progression is observed, radiation therapy is the usual treatment of choice. Since melanomas are relatively radioresistant, high doses of radiotherapy typically must be administered. The preferred method is plaque brachytherapy. In brachytherapy, radioactive seeds are implanted in close proximity to the tumor. Thus, very high doses of radiation can be administered to the tumor while sparing nearby healthy tissue. In plaque brachytherapy, a small disc is custom made that is shaped to the tumor in which the seeds are seated. Ruthenium-106 is the most frequently used radio-isotope.
The alternative to brachytherapy is the use of proton beam radiation therapy which has become available in recent years. (We described this in a prior article.) Also used is regular stereotactic radiation therapy with a linear accelerator. If these modalities cannot be used, then surgery remains an option. Local tumor resections are occasionally possible, but much more common is total enucleation of the affected eye.
About 50% of treated patients will ultimately develop metastases and over 90% of these metastases will be to the liver. The median time to progression is three years but recurrences can occur up to seven years after initial treatment. Only about 5% of uveal melanomas present initially with metastatic disease.
The prognosis for those with metastatic disease has typically been dismal, with a life expectancy in the six-to-12-month range. A new drug, tebentafusp (Kimmtrak), has significantly changed this prognosis to over two years. The drug was approved for use by the FDA two years ago. A paper was published in October 2023 in the New England Journal of Medicine that reported on a phase 3 trial of tebentafusp in which 252 patients with metastatic uveal melanoma were randomized to tebentafusp or the investigator’s choice of pembrolizumab, ipilimumab or dacarbazine with a minimum follow-up of 36 months. At 36 months, the survival in the tebentafusp arm was 27% versus 18% in the control group. The overall survival was 21.6 months for tebentafusp versus 16.9 months for the control group.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
