Survival Benefit of Primary Tumor Treatment in Uveal Melanoma: A Re-Analysis of the Collaborative Ocular Melanoma Study (COMS) and Natural History Study (NHS) Cohorts

Objective: To evaluate whether primary tumor treatment provides a survival benefit in uveal melanoma by comparing patients who declined treatment (Natural History Study, NHS) with those who received treatment in the Collaborative Ocular Melanoma Study (COMS) for medium-sized choroidal melanomas. Methods: Individual-level survival data were reverse-engineered from cumulative all-cause mortality curves in the original COMS and NHS publications. Censoring patterns were estimated from numbers at risk and descriptive statistics. A Bonferroni-corrected significance level of 0.017 was applied. Additionally, to ensure a conservative approach, NHS cohort data were iteratively adjusted by reducing the 8-year cumulative mortality by one percentage point if the Cox regression hazard ratio for all-cause mortality, the unadjusted risk ratio for death, and the 95% confidence intervals (CIs) of the Kaplan–Meier curves did not show a smaller survival difference than originally reported. Results: Kaplan–Meier analysis revealed significantly higher cumulative mortality in the NHS cohort compared to the COMS cohort (log–rank p = 0.012). When restricting the analysis to the first 8 years to account for unclear censoring patterns beyond this period, the NHS cohort still demonstrated worse survival (p = 0.008). A sensitivity analysis, varying censoring times by ±25% over 1000 iterations, confirmed worse survival in the NHS cohort in 100% of cases. Conclusions: In this re-evaluation, patients who declined treatment for medium-sized choroidal melanomas had significantly worse survival, suggesting a potential survival benefit of primary tumor treatment.