Malignant Transformation of Choroidal Indeterminate Melanocytic Tumors

Importance The accuracy of the predicted risk of malignant transformation of a large choroidal nevus or indeterminate melanocytic tumor (IMT) is not known. Objective To estimate the risk of malignant transformation (predicted risk) in a cohort of patients with IMT of known outcomes (observed status; benign [large nevus] or malignant [small melanoma]). Design, Setting, and Participants This was a cohort study of patients from a single center. Patients diagnosed with IMTs that were benign (large nevus) or malignant (small melanoma) were included in the analysis. Those lesions classified as large nevus (benign; 0% risk) had documented stability over 24 or more months. IMTs classified as small melanoma (malignant; 100% risk) had quantified growth or confirmatory pathology. Data were analyzed from October to December 2024. Exposures Prediction of malignant transformation of a large choroidal nevus or IMT. Main Outcomes and Measures The primary outcome included the predicted 5-year Kaplan-Meier probability of malignant transformation using combinations of risk factors of predictive models, the Collaborative Ocular Melanoma Study (COMS) and Wills Eye Hospital (WEH) model. Results A total of 123 patients (median [IQR] age, 63 [56-67] years; 89 male [72%]), 62 with large nevus and 61 with small malignant melanoma, were included in this study. The mean predicted 5-year Kaplan-Meier probability of melanoma for observed melanoma was 0.39 (95% CI, 0.32-0.46) by the COMS model and 0.44 (95% CI, 0.39-0.49) by the WEH model. The difference of −0.05 (95% CI, −0.14 to 0.04) was not statistically significant. However, the mean predicted 5-year Kaplan-Meier probability of melanoma for observed nevus was 0.18 (95% CI, 0.12-0.23) by the COMS model and 0.31 (95% CI, 0.24-0.38) by the WEH model. The difference of −0.13 (95% CI, −0.22 to −0.05) was statistically significant. There was a significant difference in mean 5-year Kaplan-Meier probability of melanoma between observed melanoma and nevus of 0.21 (95% CI, 0.12-0.31) by the COMS model and 0.13 (95% CI, 0.05-0.21) by the WEH model. Optimal cut points of 0.18 and 0.34 for the COMS model and the WEH model, respectively, were identified using the Youden index. The sensitivity was lower for the COMS model than the WEH model (−15.2% difference; 95% CI, −25.6% to −4.8%), and the specificity was higher for the COMS model than the WEH model (11.7% difference; 95% CI, 2.0%-21.4%). Conclusions and Relevance Findings of this cohort study suggest that predicted risk for malignant transformation estimated by 2 different models based on combinations of risk factors was suboptimal and may lead to overtreatment in approximately 30% of patients. These findings support pursuing other methods for prediction that should be validated before use in clinical practice.