Small High-Risk Uveal Melanomas Have a Lower Mortality Rate.

Rumana N Hussain,Carl Groenewald,Azzam F G Taktak,Sarah E Coupland,Helen Kalirai,Bertil E Damato,Heinrich Heimann,Antonio Eleuteri

doi:10.3390/cancers13092267

Abstract

Simple SummaryThe 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.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’.

Highlights

To address the question of whether earlier treatment of uveal melanomas (UM) would result in a reduction in mortality from metastatic melanoma, we present an analysis of the outcomes of UM patients with high-risk monosomy 3 UM (M3-UM), comparing their absolute risks of mortality according to tumor size
Our study has shown that treatment of small M3-UM is potentially lifesaving in its early stages
There appears to be a survival benefit in treating all small UM to reduce the flow of metastatic cells and, more controversially, perhaps small disomy 3 (D3) UM to prevent conversion from low- to high-risk tumor characteristics, such as in those cases of developing genetic heterogeneity

Summary

Introduction

The success of local control of primary uveal melanoma (UM) with radiotherapy or surgery is high (80–100%, depending on treatment modality) [1,2,3,4,5,6]. Recent advances in treatment regimens and the advent of intraocular laser therapies and drugs have increased the rates of eye- and vision retention [7,8,9,10,11]. Clinical trials are underway for other treatments for patients with metastatic disease [26]; to date, the prognosis remains poor and the metastatic mortality rate associated with UM remains at 40–45% [27,28,29,30,31]

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