Patients presenting with stage IV uveal melanoma: Lessons learned

Challenges persist in identifying patients with stage IV uveal melanoma. While clinical, histopathologic, and genetic features of the primary tumor have been shown to provide prognostic value for assessing metastatic risk, biopsy-related genetic analyses are expensive and not universally available. Therefore, this review will focus on clinical characteristics. Initial staging and follow-up screening protocols have evolved for patients with uveal melanoma. The Collaborative Ocular Melanoma Study (COMS) required a physical examination, chest X-ray, and hematologic survey (primarily liver function tests). Though these studies were found to have a high specificity, COMS investigators typically found late-stage metastases. More recently, protocols have concentrated on liver imaging (abdominal ultrasound, computed tomography, and magnetic resonance imaging). Though hepatic radiographic imaging has been found more likely to reveal earlier metastatic uveal melanoma, by definition it cannot detect most extrahepatic and multiorgan metastases. An international multicenter registry study recently focused on patients who were diagnosed with stage IV uveal melanoma simultaneously with their primary intraocular melanoma. Therein, utilizing center-specific diagnostic methods, stage IV was found to occur in about 2% of patients. However, subgroup analysis found that a disproportionate number of multi-organ metastases were discovered when whole-body positron emission tomography/computed tomography was used for staging. Herein, we review the literature on patients who present with stage IV uveal melanoma, how they were detected, and their outcomes.