Metastatic Risk Factors Associated with Class 1A Uveal Melanoma Patients.

Yong Qin,Maura S. Glover,Sapna P. Patel,Alexej Ballhausen,Dan S. Gombos,Michelle Williams,Elizabeth Urias,Stephen K. Gruschkus

doi:10.3390/cancers13133292

Abstract

Simple SummaryUveal melanoma (UM), patients with Class 1A gene expression profiling (GEP), have a lower metastatic risk (2% at 5 years) compared to Class 1B or Class 2 patients. However, further risk stratification could help to adapt follow-up intervals in Class 1A UM patients according to their metastatic risk. Our single-center IRB-approved retrospective case series review of 73 Class 1A UM patients aimed to identify risk factors associated with metastasis development and overall survival. We show that Class 1A UM patients with stage III disease and/or large COMS size are at elevated risk for metastasis. Combined clinical decision-making utilizing AJCC stage and COMS size could have a significant clinical impact by improving risk stratification and adapting follow-up intervals in Class 1A UM patients.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.

Highlights

Uveal melanoma (UM) is the most common primary malignancy of the eye
Mutation status was missing for most patients as it does not play a role in primary UM management, and the tumor was unavailable for sequencing in the majority of cases
In multivariable analyses of time to distant metastasis (TTDM), to distant or local recurrence (TTR), and overall survival (OS), we found that American Joint Committee on Cancer (AJCC) stage was significantly associated with TTDM, while primary therapy was significantly associated with OS (Figure 4)

Summary

Introduction

Uveal melanoma (UM) is the most common primary malignancy of the eye. The metastatic disease most commonly affects the liver and is fatal in approximately 50% of patients [1]. As the vast majority of patients present without evidence of metastatic disease at the time of diagnosis, stratification of metastatic risk can significantly influence the interval and length of surveillance. A prognostic molecular test based on gene expression profiling (GEP) has been proposed, validated prospectively, and is in common use to assess metastatic risk [2,3,4,5]. The GEP assay uses a PCR-based 15-gene array to classify tumors as Class 1 (low metastatic risk) or Class 2 (high metastatic risk). In contrast to Class 1A and 1B tumors, Class 2 tumors present with a significantly higher metastatic risk (50% risk of metastasis at 3 years and 72% at 5 years) [3]. While PRAME-positive Class 1 UM patients might be at elevated risk for metastasis, PRAME positivity might correlate with a shorter time to metastasis in Class 2 UM patients [10,11]

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