To date, melanomas of the eye have resisted the revolutionary strides made in treating cutaneous melanomas over the past five years. Although uveal melanoma, the most common primary intraocular malignancy, has many similarities to its cutaneous counterpart, it differs in key ways that present barriers to progress.
First, it can be less conspicuous to detect. While most cutaneous melanomas are readily discovered on the skin surface, only about 5 percent of uveal melanomas arise in the iris, where they can be easily found by routine ophthalmic examination of the outer eye. More than 90 percent arise behind the pupil, where they can only be visualized with special tools. This has especially been a problem for males, who are less likely to go in for routine eye examination; they are typically diagnosed at a later stage, after they come in reporting visual symptoms.
Uveal melanomas also exhibit a higher proclivity than cutaneous melanomas for eventual metastasis. Though over 90 percent of patients have no evidence of metastatic disease when diagnosed, half of all patients ultimately develop metastatic disease. Five-year mortality rates, far greater than for cutaneous melanomas, are about 15 percent for small tumors, 30 percent for medium tumors and 50 percent for large tumors.
Finally, no effective therapy has yet been found for metastatic disease; the great successes achieved in cutaneous melanoma with checkpoint blockade and targeted therapies have not translated well to uveal melanoma.
The situation could improve in the near future. Recent advances in our understanding of the biology and molecular pathogenesis of uveal melanoma have begun to yield important insights that could improve prognostic accuracy and are laying the groundwork for exciting new therapy approaches for advanced disease.
In this issue of The Melanoma Letter, Drs. Francis, Shoushtari, Barker and Abramson present a wonderful review of our current knowledge of uveal melanoma, from the etiological and genetic underpinnings of the disease to the important refinements being made in metastatic risk assessment and management. They report on the state-of-the-art, eye-saving advances made in treating primary disease and both the existing limitations and rising potential for treating advanced disease.
In our second story, Matthew Field and Drs. Tarlan and Harbour report on the most promising directions in research for diagnosis, prognosis and management of high-risk and advanced metastatic uveal melanoma, exploring recent discoveries in the molecular pathogenesis of the disease that are beginning to impact on treatment. They discuss the use of molecular biomarkers and gene expression profiling to enhance prognostication, the advent of hepatic artery embolization and combination drugs to enhance immunotherapy and the discovery of specific mutations that provide a framework for targeted molecular therapy.
With the increasingly precise methods for narrowing in on prognosis and a burgeoning understanding of the role of driver mutations and immune surveillance, uveal melanoma patients with advanced disease have their first real hope for improved therapeutic options.
Allan C. Halpern, MD • Editor-in-Chief
Ashfaq A. Marghoob, MD • Associate Editor