Metastatic Risk Factors Associated with Class 1A Uveal Melanoma Patients

Abstract

In uveal melanoma (UM), gene expression profiling (GEP) is commonly used to classify metastatic risk into three groups (Class 1A, 1B, and 2). Class 1A patients have a lower metastatic risk of 2% at 5 years compared to other groups. We aimed to describe clinical features associated with the development of metastasis in this low-risk group. This single-center IRB-approved retrospective case series review included all UM patients between February 2006 and March 2019 with an archived or fresh specimen classified as Class 1A. Cox regression and receiver operating characteristics analyses were used to identify factors associated with metastasis development and OS. Among 73 UM patients with Class 1A, the 5-year cumulative incidence of local recurrence and distant metastasis was 4.2% and 17.0%, respectively. Stage III disease (HR 20.7; 95% confidence interval (95% CI) 1.4-300.6; p = 0.0264) was found to be independently associated with metastatic recurrence, while primary therapy was associated with OS (enucleation vs. brachytherapy, HR 13.5; 95% CI 1.3-147.6; p = 0.0348). Combined clinical decision-making utilizing factors such as GEP class, American Joint Committee on Cancer (AJCC) stage, and COMS size could have a significant clinical impact by improving risk stratification and adapting follow-up intervals in UM Class 1A patients.

Keywords: Class 1A; GEP; metastasis; risk factors; uveal melanoma.

Figure 1

Cumulative incidence (CI) of distant metastasis, local recurrence, and combined distant metastasis and local recurrence is shown (top panel), including estimates for 1, 2, 3, and 5 years (bottom panel) in patients with Class 1A UM. Abbreviations: HR, Hazard ratio; LL, Lower limit; UL, Upper Limit; CI, Confidence interval; Cumulative incidence.

Figure 2

Overall survival for Class 1A UM patients who did (red line) or did not (blue line) develop distant metastasis is shown (top panel), including estimates for 1, 2, 3, and 5 years (bottom panel). Abbreviations: HR, Hazard ratio; LL, Lower limit; UL, Upper Limit; CI, Confidence interval.

Figure 3

(A). Cumulative incidence of distant metastasis for patients with AJCC stage I/II disease (solid line) and AJCC stage III disease (dashed line) is shown (top panel), including estimates for 1, 2, 3, and 5 years (bottom panel). (B). Cumulative incidence of distant metastasis for patients with small/medium COMS size (solid line) and large COMS size (dashed line) is shown (top panel), including estimates for 1, 2, 3, and 5 years (bottom panel). Abbreviations: COMS, Collaborative Ocular Melanoma Study; HR, Hazard ratio; LL, Lower limit; UL, Upper Limit; CI, Confidence interval.

Figure 4

Forest plot of TTDM, TTR, and OS. Significant p-values are shown in bold and italic. Abbreviations: TTDM, Time to distant metastasis; TTR, Time to local or distant recurrence; OS, Overall survival; HR, Hazard ratio; CI, Confidence interval.

Figure 5

Time-dependent AUC for receiver operating characteristics (ROC) of multivariate model for distant metastasis is shown (top panel), including ROC curves at 1, 2, and 3 years (bottom panel). Abbreviations: AUC, Area under the curve; ROC, Receiver operating characteristics.