Study Highlights Benefits of Observation vs. Treatment for High-Risk Choroidal Nevi

Researchers propose that instead of promptly treating patients who present with high-risk choroidal nevi, monitoring tumor growth rates may serve as a valuable noninvasive biomarker to inform the decision on when to initiate treatment.  Photo: Mark T. Dunbar, OD. Click image to enlarge. In a recent study published in American Journal of Ophthalmology, researchers sought to evaluate the genetic profiles and metastasis rates of high-risk choroidal nevi that were initially observed (IO) vs. those that received immediate treatment (IT) upon uveal melanoma diagnosis. The findings suggested that patients in the IO group exhibited a lower risk of metastasis and a more favorable genetic profile compared to those in the IT group, supporting the clinical hypothesis that smaller lesions, when monitored appropriately, might not require immediate intervention.The study was conducted as a retrospective clinical cohort analysis, focusing on 272 patients diagnosed with uveal melanoma at a single ocular oncology practice in Houston, Texas, between 2013 and 2022. Participants were divided into two main groups—IO and IT—based on their management approach. Patients in the IT group had their melanomas diagnosed at the initial consultation, while the IO group comprised individuals diagnosed with high-risk choroidal nevi (typically with thickness <2.0mm) who were monitored over time until clinical criteria for uveal melanoma were met.The results revealed that the IT group had larger tumors upon diagnosis, with a substantially higher rate of Gene Expression Profiling (GEP) Class 2 tumors (indicating high metastatic risk)—32.9% compared to 13.6% in the IO group. Furthermore, 35.2% of patients in the IT group tested positive for preferentially expressed antigen in melanoma (PRAME), indicating a more aggressive tumor behavior than their counterparts in the IO group, who showed a lower PRAME positivity of 20%. Among the most compelling findings from the study is that only 5.1% of patients in the IO group went on to develop metastatic disease, a stark contrast to the 18.8% in the IT group.According to the authors, these findings suggest that “patients who present to the ocular oncologist with larger melanomas requiring immediate treatment have genetically more advanced, more aggressive tumors.” Therefore, the authors argue the potential advantages of a conservative monitoring strategy for high-risk lesions, noting that careful observation can often lead to favorable outcomes without the immediate need for aggressive treatments.“Observation for high-risk lesions until documented growth at a certain growth rate threshold may be a reasonable and lower-risk strategy in appropriately selected patients, although a small percentage of patients may still develop metastatic disease,” the researchers explained in their paper. They went on to add, “Since metastatic disease progresses inefficiently and tumors grow slowly, a treatment delay of several weeks to months is unlikely to have a substantial impact on mortality.”The study authors concluded that while further research is needed, tumor growth rate—as opposed to the presence of absolute growth in an unspecified time period—”may provide a comparative baseline for future studies and a possible benchmark for clinicians to use as a non-invasive biomarker to guide the initiation of treatment in an effort to minimize genetic evolution to a Class 2 genotype and an increased risk of metastatic death.”Click here for the journal source. Kadakia AB, Ali AM, Chuang AZ, Schefler AC. Comparison of patients with observed high-risk choroidal nevi that evolved into melanomas vs. patients with immediately treated uveal melanomas. Am J Ophthalmol. June 2025. [Epub ahead of print].