Predicted metastasis-free survival based on gene expression profiling may not be accurate

Arun Singh, MD, from the Department of Ophthalmology, University of Iowa, Iowa City, and colleagues called into question the accuracy of predicted metastasis-free survival based on a commercially available gene expression profiling test in patients with uveal melanoma.

The investigators suggested that the predicted metastasis-free survival for metastatic tumors may be worse than what they and other research groups have observed.

They conducted a cohort study¹ to compare the predicted metastasis-free survival with the observed metastasis-free survival in patients in this cohort and with those in previously published studies.

The investigators described that their cohort study included patients from the University of Iowa and Cleveland Clinic who had been diagnosed with uveal melanoma who underwent prognostic fine-needle aspiration biopsy at the time of primary treatment. The patients were recruited from December 2012 to December 2020.

The predicted metastasis-free survival for the patients was taken from the gene expression profiling report. The observed metastasis-free survival was defined as the time to metastasis.

The overall estimate of the published metastasis-free survival was obtained from a meta-analysis of published data.

Metastasis-free survival findings

The cohort study included 92 patients from the University of Iowa and 255 patients from the Cleveland Clinic. The mean patient age at diagnosis was 59.4 years.

Singh and colleagues reported that the observed metastasis-free survival for patients with a class 2 tumor in this cohort was 67% at 3 years and 47% at 5 years. In the published studies, the respective rates at 3 and 5 years were 62% and 40%, which were better than those predicted, i.e., 50% and 28% for 3 and 5 years, respectively.

Among the patients with a class 2 tumor, those with metastasis had larger tumors compared with nonmetastatic tumors. The authors found that the mean largest basal diameter difference was 1.7 mm and the mean thickness ratio, was 1.3 (P  =  0.01 for both comparisons). An increasing tumor size was associated significantly with an increased hazard ratio of metastasis (1.16; P <  0.001).

The investigators suggested that adding the tumor size into the prediction model may enhance the model’s accuracy. Adjuvant therapy trials may not be able to rely on predicted metastasis-free survival to calculate efficacy with a high degree of confidence, they pointed out.

Reference

Singh AD, Binkley EM, Wrenn JM, et al. Predicted vs observed metastasis-free survival in individuals with uveal melanoma. JAMA Ophthalmol. 2022;140(9):847-854. doi:10.1001/jamaophthalmol.2022.2623