Small High-Risk Uveal Melanomas Have a Lower Mortality Rate

SIMPLE SUMMARY: The current paradigm concerning metastatic spread in uveal melanoma is that the critical point for dissemination occurs prior to presentation and that treatment of the primary tumor does not change outcome. However, we show that patients with small uveal melanomas with genetic characteristics typical for high risk for metastatic disease have a lower mortality rate from metastatic disease, if treated earlier. Our data demonstrate that such small melanomas are potentially lethal (like larger tumors), but that there is a window of opportunity to prevent life-threatening metastatic spread if actively treated, rather than being monitored, as is often done currently. ABSTRACT: Our aim was to determine whether size impacts on the difference in metastatic mortality of genetically high-risk (monosomy 3) uveal melanomas (UM). We undertook a retrospective analysis of data from a patient cohort with genetically characterized UM. All patients treated for UM in the Liverpool Ocular Oncology Centre between 2007 and 2014, who had a prognostic genetic tumor analysis. Patients were subdivided into those with small (≤2.5 mm thickness) and large (>2.5 mm thickness) tumors. Survival analyses were performed using Gray rank statistics to calculate absolute probabilities of dying as a result of metastatic UM. The 5-year absolute risk of metastatic mortality of those with small monosomy 3 UM was significantly lower (23%) compared to the larger tumor group (50%) (p = 0.003). Small disomy 3 UM also had a lower absolute risk of metastatic mortality (0.8%) than large disomy 3 UM (6.4%) (p = 0.007). Hazard rates showed similar differences even with lead time bias correction estimates. We therefore conclude that earlier treatment of all small UM, particularly monosomy 3 UM, reduces the risk of metastatic disease and death. Our results would support molecular studies of even small UM, rather than ‘watch-and-wait strategies’.