Advances in ocular melanoma research are helping physicians better predict which patients are at higher risk for metastasis after treatment of the primary tumor. A recent study led by Dr. J. William Harbour of UT Southwestern Medical Center and published in Nature Communications highlights a new approach to uveal melanoma risk prediction by combining two genetic tests: the DecisionDx-UM gene expression profile and PRAME testing.
Uveal melanoma, the most common form of ocular melanoma, originates in the eye but carries a significant risk of spreading to other organs, particularly the liver. One of the greatest challenges in managing this disease is determining which patients may already have microscopic cancer cells that have spread beyond the eye but remain undetectable on imaging scans.
The COOG2 study demonstrated that combining the DecisionDx-UM test with PRAME expression analysis offers a more accurate prediction of metastasis risk than traditional DNA mutation testing alone. While standard sequencing focuses on tumor DNA mutations, the DecisionDx-UM test evaluates the tumor’s gene expression profile, including how cancer cells interact with the surrounding immune environment. Adding PRAME testing further refines this risk assessment.
For patients, this improved risk prediction has significant clinical implications. Individuals classified as low risk may only require periodic imaging, such as annual liver scans, providing reassurance while maintaining careful monitoring. For patients identified as high risk, physicians can implement more aggressive surveillance strategies, including frequent liver imaging every few months during the first several years after diagnosis.
Perhaps most importantly, identifying high-risk patients early allows physicians to discuss preventive treatment options and clinical trials designed to reduce the chance of metastatic disease. For example, researchers are investigating targeted therapies such as quisinostat, a drug designed to reverse some of the molecular changes seen in aggressive class 2 uveal melanoma tumors. Clinical trials are underway at several cancer centers to evaluate whether these therapies can improve long-term outcomes.
Other approaches include studying immunotherapies such as tebentafusp (Kimmtrak) in earlier stages of disease, including the adjuvant setting after treatment of the primary eye tumor.
Overall, the findings from this study represent an important step forward in personalized medicine for ocular melanoma patients. By combining genetic tests to better understand tumor biology, doctors can provide more precise surveillance plans, guide clinical trial enrollment, and potentially improve survival outcomes for patients living with uveal melanoma.