Comparison of Patients with Observed High-Risk Choroidal Nevi That Evolved into Melanomas vs. Patients with Immediately Treated Uveal Melanomas.

Purpose: Patients who present with high risk choroidal nevi, typically with thickness < 2.0 mm, are thought to have a better prognosis than patients who present with larger tumors. Large scale studies have not explored the differences in genetics between melanocytic lesions that were initially observed (IO) and those immediately treated (IT). The primary objective of this study is to compare genetics and metastatic rate between high risk nevi initially observed and treated upon growth vs. immediately treated uveal melanoma (UM). The secondary objective is to evaluate the growth rate of high-risk lesions in the IO group that eventually triggered treatment, and to assess whether this growth rate threshold was sufficient to maintain a low rate of metastasis DESIGN: Retrospective clinical cohort study SUBJECTS: 272 patients with uveal melanoma (UM) who underwent treatment at a large ocular oncology practice in Houston, Texas between 2013 and 2022 with at least 18 months follow-up.

Main outcome measures: Tumor Gene Expression Profile (GEP), Tumor PReferentially Expressed Antigen in MElanoma (PRAME) status, Tumor height and largest base diameter (LBD) growth rate [millimeters (mm)/year], presence of metastasis (yes or no) METHODS: Patients were categorized as IO or IT. Patients in the IO group were initially diagnosed with high risk choroidal nevi and monitored until clinical criteria for UM were met. In contrast, patients in the IT group were diagnosed with UM upon their first visit by the ocular oncologist. Metastatic outcomes, genetic expression, and tumor growth rates were analyzed.

Results: 213 patients in IT and 59 in IO were included. Compared to IO patients, IT patients had higher percentages of metastasis (p=0.009), Gene Expression Profile (GEP) Class 2 tumors (p=0.010), and PReferentially Expressed Antigen in MElanoma (PRAME) expression (p=0.044). Mean tumor growth rate in the IO group increased just before treatment decision by 0.65 and 1.00 mm/year for height and largest base diameter, respectively (p<0.01).

Conclusions: Genetic profiles and metastatic potential evolve alongside tumor growth, indicating a transition from high risk nevi to UM. Monitoring the growth rate of high risk nevi serves as a reliable noninvasive biomarker for identifying nevus transformation to UM and for guiding clinical decision-making, without resulting in a high rate of Class 2 tumors and metastatic disease.