Collaborative Ocular Oncology Group study 2 (COOG2): Prospective multi-center validation of the 15-gene expression profile (GEP)/PRAME molecular prognostic tool for uveal melanoma in 1586 patients

Abstract

Purpose : To validate the accuracy of the 15-GEP/PRAME enhanced prognostic tool for uveal melanoma (UM) in a prospective, multi-center setting.

Methods : The Collaborative Ocular Oncology Group Study Number 2 (COOG2) enrolled 1586 patients with UM involving the choroid and/or ciliary body across 26 ocular oncology centers in the United States and Canada between April 2017 and April 2020. Each center obtained IRB approval. All patients underwent testing for the 15-GEP and PRAME expression status (negative or positive) using the DecisionDx-UM^TM and DecisionDx-PRAME^TM (Castle Biosciences, Inc., Friendswood, TX) tests, respectively. Primary endpoint was metastasis-free survival (MFS).

Results : Among 1586 patients enrolled in the study, 15-GEP was Class 1 in 1084 (68.3%) and Class 2 in 502 (31.7%) patients. PRAME status was negative in 1111 (70.1%) and positive in 475 (29.9%) patients. Class 1 tumors were subclassified as Class 1A in 694 (43.8%) and Class 1B in 390 (24.6%) patients. Five-year MFS was 95.6% (95% CI, 93.9-97.4) for Class 1/PRAME-, 80.6% (73.9-87.9) for Class 1/PRAME+, 57.6% (50.6-65.7) for Class 2/PRAME-, and 44.8% (38.0-52.8) for Class 2/PRAME+ (see Figure). MFS was not significantly different between Class 1A and Class 1B (Chi-squared = 0.16784, df = 1, P = 0.682). In multivariable Cox proportional hazards analysis, 15-GEP was the most robust independent predictor of MFS (HR 6.03; 95% CI, 4.49-8.09); P<0.001), followed by PRAME status (HR 1.77; 95% CI, 1.39-2.27; P<0.001). The only clinical feature demonstrating prognostic value independent of 15-GEP and PRAME was tumor diameter (C-statistic, 0.81 versus 0.85, respectively; P<0.001).

Conclusions : In the largest and most representative prospective multicenter biomarker study to date in UM, the prognostic accuracy of 15-GEP was confirmed, and the independent prognostic value of PRAME status was validated. PRAME status was shown to be superior to the 1A/1B system for class 1 tumors. The integration of 15-GEP and PRAME into a single prognostic classifier renders clinical prognostic factors superfluous except for tumor diameter. This prognostic system sets a new standard of prognostic accuracy in uveal melanoma.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.