15-gene expression profile and PRAME as an integrated prognostic test for uveal melanoma: First report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1)

Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression, and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier.

Methods
This study included 1577 subjects with UM enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 centers. All subjects underwent testing of their primary UM sample with DecisionDx-UM (Class 1A, Class 1B, or Class 2) and DecisionDx-PRAME (negative or positive). This testing was performed by the Castle Biosciences CAP-accredited, CLIA-certified laboratory, as per standard of care. Baseline and follow-up ophthalmic visits were performed as per standard of care at each center but typically included a comprehensive ophthalmic examination, fundus photography, optical coherence tomography, and ultrasonography performed at least every 3-4 months for the first year after treatment, every 4-6 months for the second year, and every 6-12 months thereafter. The primary endpoint was metastasis-free survival (MFS).