Uveal Melanoma Tumor Size A Metastasis Predictor

Tumor size is a key predictor of metastasis, and integrating size-related risk with gene expression profile may improve prediction.

Uveal melanoma tumor size is the most significant predictor of metastasis, and can contribute information to enhance prognostic predictions from gene expression profile (GEP) tests, according to a study published in Ophthalmology

Researchers analyzed electronic health records for individuals with posterior uveal melanoma who were examined and treated at Yale New Haven Hospital from 2010 to 2021, the University of California, San Diego between 2006 and 2020, and Memorial Sloan Kettering Cancer Center from 2005 to 2020. The study included 337 participants (mean age, 61.8 [SD 15.6] years; mean; tumor thickness 6.17 [SD 4.0] mm; 55.5% men, 44.5% women). Of the total, 87 acquired metastases at an average of 37.2 (SD 40.2) months, and follow-up for those without metastases was 55 (SD 49.3) months.

Among the long-term study’s overall key results was that uveal melanoma tumor size was the “most significant predictor” of metastasis, and lesion size added forecasting benefit independent of GEP. Specifically, after univariate and multivariate analyses, the two main independent predictors of metastasis were GEP 2 class and tumor size — with size represented by either thickness or American Joint Committee on Cancer (AJCC) stage.

Increasing evidence suggests that tumor size contributes to the risk of metastasis independent of molecular classification.

The researchers uncovered no statistical differences in risk or 5-year metastasis-free survival (MFS) rates between the odds of metastasis for patients with GEP 1A and GEP 1B tumors (P =.82) and MFS (P =.80). The MFS rate for GEP 1A tumors proved to be 90.0% (83.6% to 96.9%), and GEP 1B 86.9% (76.7 to 98.5%). However, 5-year MFS for GEP 2 tumors was notably lower, 47.5% (36.0% to 62.8%).

Considering both independent predictors, the study shows GEP 1 tumors that were 9.0 mm thick or thicker had a higher hazard ratio (HR, 2.07 [0.86 to 4.99]) than GEP 1 lesions thinner than 9.00 mm. Additionally, GEP 2 tumors that were 7.0 mm or thicker had higher odds of metastasis than tumors thinner than 7.0 mm (HR, 3.23 [1.61 – 6.51]), the study shows.

“Increasing evidence suggests that tumor size contributes to the risk of metastasis independent of molecular classification,” according to the researchers. “We found that incorporating tumor thickness into the GEP classification provides additional prognostic utility. In fact, tumor size (based on thickness or AJCC staging) provided better prediction of metastasis than GEP classification. These findings are in contrast to prior studies which have demonstrated a significant but minimal benefit to incorporating tumor size into GEP classification.”

Prior research has revealed that a tumor can contain clones from both high- and low-risk subtypes, so fine needle aspiration may miss what can be detected with a larger tissue sample — DNA methylation is an option to find an aggressive subclone, the study explains. “The ability of molecular analysis to stratify tumors into distinct prognostic groups led to the hypothesis that prognosis is set in stone,” according to the investigators. “However, presence of intratumor heterogeneity suggests otherwise; low-risk tumors may harbor high-risk cells and can, in theory, progress to acquire more metastatic tendencies.”

Limitations of this analysis comprised its retrospective design, as well as that data generated at 3 institutions was dependent on tumor measurements and biopsy methods of various investigators. Conversely, strengths involve a real-world cohort undergoing UM workup. Also, the present GEP 2 metastasis rate findings concur with other recent studies.


Miguez S, Lee Y, Chan AX, et al. Validation of the prognostic utility of the gene expression profiling test in patients with uveal melanoma. Ophthalmol. Published online February 3, 2023. doi:10.1016/j.ophtha.2023.01.020