Estimating Cured Fractions of Uveal Melanoma

Abstract

The extent to which uveal melanoma is cured by ocular therapy is not known. To estimate cured fractions (CF) of uveal melanoma using combination of institutional and Surveillance, Epidemiology, and End Results (SEER) data. Integrative analysis of 42 years of SEER data (1975-2016) with 25 years (1993-2018) of complementary institutional data. The analysis included SEER US patients and molecularly prognosticated patients in the United States and Europe. Three SEER databases (SEER-9, SEER-13, and SEER-18) were merged. A total of 10 678 SEER cases of uveal melanoma diagnosed from 1975 to 2016 using International Classification of Disease for Oncology morphology codes 8720-8790 (for melanoma) and site codes C69.2-4 (for choroid, ciliary body, and iris) were downloaded April 16, 2019. The institutional data included 5 institutional cohorts of 788 molecularly prognosticated patients (diagnosed prior to July 2019) with 3115 person-years at risk of death and 262 observed deaths. Excess absolute risks of death (EAR) and cured fraction (CF) indicates lifetime area under the EAR curve. These are applied to populations and subpopulations. The SEER EAR, with sexes and races pooled, can be modeled as a sum of 2 waves. The first wave peaks at approximately 3 years and is negligible by 15 years, at which time the second wave peaks. Institutional data suggest that the first wave is owing to BAP1 mutant cases (204 of 355 [57.5%]; 95% CI, 52%-63%) and that the second wave is owing to BAP1 wild-type SF3B1 mutant cases (60 of 355 [17%]; 95% CI, 13%-21%). There is also a third group with a low flat EAR time course (91 of 355 [25.5%]; 95% CI, 21%-30%). The overall statistical CF of 60% is reached by approximately 25 years. These findings suggest that the benefits of ocular therapy for curing uveal melanoma may be questionable because statistical cures reflect deaths of poor prognosis cases and survival of good prognosis cases. Changes in uveal melanoma patient management may be needed to improve survival.