Abstract
AIM: The collaborative ocular melanoma study (COMS) reported similar survival between plaque brachytherapy (a type of interventional radiotherapy) and enucleation for medium-sized choroidal melanomas. We aimed to quantify the mortality differences required to achieve statistical significance and assess the robustness of these thresholds. METHODS: We reanalyzed 12-year mortality data from COMS using threshold analysis to determine how many additional or fewer deaths in either treatment arm would shift the lower bound of the 95% confidence interval (CI) for the risk ratio above 1. RESULTS: At 12 years, there were 105 melanoma-related deaths in the brachytherapy arm and 98 in the enucleation arm (risk ratio 1.08, 95% CI 0.82-1.42). Achieving statistical significance would have required 31 additional deaths in the brachytherapy arm or 23 fewer in the enucleation arm; conversely, favoring brachytherapy would have necessitated 34 additional deaths in the enucleation arm or 27 fewer in the brachytherapy arm. These thresholds remained consistent across power levels and sensitivity scenarios. CONCLUSIONS: The COMS trial did not reveal a clinically meaningful survival difference. Our findings underscore the substantial mortality shifts required for statistical significance and highlight the challenges in detecting modest treatment effects in uveal melanoma trials.