Long-term outcomes in a population-based cohort of 2,967 uveal melanoma patients clinically tested with the 15-gene expression profile: A collaborative study with the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program Registries.
Authors: Cook Robert W. , Petkov Valentina I. , Byun Jung S. , Bailey Christine N. , Rogers Jason H. , Kurley Sarah J. , Covington Kyle R. , Alsina Katherina M. 
Published: June 2023

e21574

Background: Metastatic risk prediction in uveal melanoma is commonly performed using a commercially available 15-gene expression profile (15-GEP) test. A recent collaborative effort with the NCI’s SEER program registries allowed for serial linkage of UM patients captured by SEER registries with clinical 15-GEP test results. The objective of this study was to confirm the 15-GEP test’s performance in clinically tested uveal melanoma patients with long-term outcomes at the population level. Methods: Following established operating procedures, SEER registries linked UM cases diagnosed from 2010–2019 to 15-GEP test results provided by Castle Biosciences using a trusted third-party (honest broker). The patients were clinically tested as recommended by guidelines (testing was performed either on fine needle aspiration biopsy tissue or formalin-fixed, paraffin-embedded tissue from enucleations). De-identified data were provided to NCI and Castle Biosciences scientists for this study. Kaplan-Meier analysis with log-rank test was used to evaluate the available endpoints of melanoma-specific survival (MSS) and overall survival (OS). Multivariable analysis was performed with Cox proportional hazards modeling. Results: A total of 2,967 UM patients ≥ 18 years of age with localized disease (excluding Stage IV) and 15-GEP test result were included in this study (Class 1, 1904; Class 2, 1063). The cohort was 51.7% male, with a median age of 63 years. Median follow-up time was 2.2 years. Patients with a low-risk (Class 1) vs. high-risk (Class 2) result had significantly higher 7-year survival outcomes (OS, 78.9 vs. 31.8%, p < 0.001; MSS, 90.4 vs. 41.6%, p < 0.001, respectively). Patients with a Class 2 result were over six times more likely to experience a UM-related death than those with a Class 1 result (31.8 [338/1063] vs. 5.0% [96/1904]; p < 0.001). Multivariable analysis showed that the 15-GEP was the strongest independent predictor of MSS when compared with clinicopathologic features (tumor diameter or thickness) and age, with a Class 2 hazard ratio of 6.2 (95% CI, 3.9–9.7; p < 0.001). Notably, there was no association between GEP class call distribution and socioeconomic status as measured by the Yost index (p = 0.79). Conclusions: In this analysis, the 15-GEP accurately stratified risk of death from UM in a clinically tested, population-based cohort of patients, confirming previous studies. Socioeconomic status did not impact the likelihood of getting a high-risk result, suggesting equitable access to care for patients who receive 15-GEP testing. Ongoing analyses of SEER-linked UM data will include patients who received a PRAME test result, allowing for assessment of this adjunctive biomarker in combination with the 15-GEP result.