4.5 Review

Metastatic uveal melanoma: The final frontier

期刊

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.preteyeres.2022.101041

关键词

Uveal melanoma; Metastasis; Surveillance; Staging; Treatment; Overall survival

资金

  1. Eye Foundation
  2. Finnish Medical Foundation
  3. Mary and Georg C. Ehrnrooth Foundation
  4. Eye and Tissue Bank Foundation
  5. Evald and Hilda Nissi Foundation
  6. Helsinki University Hospital [2020315]
  7. Southern Ostrobothnian Central Hospital Research Funds

向作者/读者索取更多资源

Treatment of primary intraocular uveal melanoma has advanced significantly, but the risk of distant metastases remains high. There is no consensus on surveillance, staging, and treatment of disseminated disease, making it difficult to improve survival rates. Solving these issues is the key to curing metastatic uveal melanoma.
Treatment of primary intraocular uveal melanoma has developed considerably, its driver genes are largely unraveled, and the ways to assess its risk for metastases are very precise, being based on an international staging system and genetic data. Unfortunately, the risk of distant metastases, which emerge in approximately one half of all patients, is unaltered. Metastases are the leading single cause of death after uveal melanoma is diagnosed, yet no consensus exists regarding surveillance, staging, and treatment of disseminated disease, and survival has not improved until recently. The final frontier in conquering uveal melanoma lies in solving these issues to cure metastatic disease. Most studies on metastatic uveal melanoma are small, uncontrolled, retrospective, and do not report staging. Meta-analyses confirm a median overall survival of 10-13 months, and a cure rate that ap-proaches nil, although survival exceeding 5 years is possible, estimated 2% either with first-line treatment or with best supportive care. Hepatic ultrasonography and magnetic resonance imaging as surveillance methods have a sensitivity of 95-100% and 83-100%, respectively, to detect metastases without radiation hazard ac-cording to prevailing evidence, but computed tomography is necessary for staging. No blood-based tests addi-tional to liver function tests are generally accepted. Three validated staging systems predict, each in defined situations, overall survival after metastasis. Their essential components include measures of tumor burden, liver function, and performance status or metastasis free interval. Age and gender may additionally influence survival. Exceptional mutational events in metastases may make them susceptible to checkpoint inhibitors. In a large meta-analysis, surgical treatment was associated with 6 months longer median overall survival as compared to conventional chemotherapy and, recently, tebentafusp as first-line treatment at the first interim analysis of a randomized phase III trial likewise provided a 6 months longer median overall survival compared to in-vestigator's choice, mostly pembrolizumab; these treatments currently apply to selected patients. Promoting dormancy of micrometastases, harmonizing surveillance protocols, promoting staging, identifying predictive factors, initiating controlled clinical trials, and standardizing reporting will be critical steppingstones in reaching the final frontier of curing metastatic uveal melanoma.

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