Metastatic Uveal Melanoma: Treatment Strategies and Survival—Results from the Dutch Melanoma Treatment Registry

Abstract

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63–14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07–4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year survival rates in selected groups of patients.

Metastatic uveal melanoma managed with best supportive care

“…Also, to the best of our knowledge, our cohort is the second largest one of patients receiving BSC for metastatic UM, and we are the first to stage them. We are aware of seven previous reports that included 11 to 191 patients with BSC [9,[20][21][22][23][24][25]. One of these studies also analysed prognostic factors and found, in line with us, that patients who received BSC had worse PS than actively treated [23].…”

“…There is no published survival data on consecutive patients managed with best supportive care (BSC) to allow historical comparison with those actively treated, although such data would be valuable for planning and analysing trials of metastatic UM, most of which continue to be non-randomised and non-comparative [8,9]. We report population-based OS according to previously validated prognostic stages [10] for patients with metastatic UM managed only with BSC.…”

Five Decades of Enucleations for Uveal Melanoma in One Center: More Tumors with High Risk Factors, No Improvement in Survival over Time

“…In the Netherlands a registry has been set up that includes UM patients with metastases. Jochems et al [47] studied this cohort, consisting of 227 patients that were included between 2012 and 2018; 175 of these patients provided complete data. Cases that were eligible for local treatment of metastases (for example, surgical resection, isolated hepatic perfusion with melphalan, radiotherapy, radiofrequency ablation) showed the best survival, with a 1-year survival of 82%, versus 49% for systemic therapy and 28% for supportive care.…”

“…These data indicate that especially young patients with a good WHO performance score and few metastatic sites are good candidates for local therapy. Although we do not know how many of the patients in their study [47] were included in our cohort, it is likely that there is overlap.…”

Uveal Melanoma

“…Toutee et al analyze the survival benefit and the risk of visual loss associated with early proton beam radiotherapy [33]. Jochems and colleagues report on treatment strategies and survival of metastatic uveal melanoma patients based on the Dutch Melanoma Treatment Registry [35]. Tura et al provide data indicating that the therapeutic antibody ranibizumab, and not bevacizumab, suppresses metabolic activity, proliferation, and intracellular Vascular Endothelial Growth Factor A, VEGF-A, levels in uveal melanoma [38].…”