Survival Benefit of Primary Tumor Treatment in Uveal Melanoma: A Re-analysis of COMS and 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: A retrospective cohort study was conducted using reverse-engineered individual-level survival data from cumulative all-cause mortality curves in the original COMS and NHS publications. Censoring patterns were estimated from numbers at risk and descriptive statistics. To ensure a conservative approach, a Bonferroni-corrected significance level of 0.017 was applied. Further, if the Cox regression hazard ratio for all-cause mortality, the unadjusted risk ratio for death at 8 years, and the 95% confidence intervals (CIs) of the Kaplan-Meier curves did not indicate a smaller survival difference for the resulting data than reported in the original studies, we iteratively adjusted the NHS cohort data by reducing the 8-year cumulative mortality by one percentage point until these criteria were met. 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). Sensitivity analysis varying censoring times by ±25% over 1,000 iterations confirmed worse survival in the NHS cohort in 100% of cases. Conclusions: Patients who declined primary tumor treatment had significantly worse survival than those who received treatment. These findings support the hypothesis that primary tumor treatment confers a survival benefit in uveal melanoma.