Delays between Uveal Melanoma Diagnosis and Treatment Increase the Risk of Metastatic Death

Abstract

To investigate if the interval between diagnosis and treatment of posterior uveal melanoma (UM) is associated with metastatic death. Retrospective, single-center cohort study. A total of 1145 patients consecutively diagnosed with posterior UM at St. Erik Eye Hospital, Stockholm, Sweden, from 2012 to 2022, with recorded dates of diagnosis and primary treatment. This cohort represents 81% of all diagnosed patients in Sweden during this period. Data on the interval between diagnosis and treatment were collected for all patients. Its prognostic importance was examined with univariate and multivariate competing risks regressions, and cumulative incidence analyses. Incidence of metastatic death (UM mortality) for patients with prompt (< 1 month from diagnosis) versus delayed treatment (≥ 1 month) and subdistribution hazard ratios (exp(βj)) for every additional 10-day delay in treatment. The mean interval between diagnosis and treatment was 34 days (SD, 56, range, 0-932). Patients treated promptly had larger tumors at diagnosis, but there were no differences in patient age, tumor distance to the optic disc, rates of ciliary body involvement (CBI) or extraocular extension (EXE), or symptom duration before diagnosis. Those who were treated more than 1 month after diagnosis had greater UM mortality in American Joint Committee on Cancer (AJCC) stage II and III. In stage I, UM mortality for delayed treatment was lower for the first 10 years, followed by a marked spike in the 11th year. In multivariate competing risks regressions of all 1145 patients with tumor diameter, thickness, CBI, and EXE as covariates, the risk for UM mortality increased with 1% for every additional 10-day delay in treatment (exp(βj) 1.01). Among 355 patients treated with enucleation, this delay was associated with UM mortality, independent of AJCC stage, cytomorphology, and level of immunohistochemical BAP-1 expression. Increasing time between diagnosis and treatment of UM is associated with a higher risk of metastatic death. These results challenge a central concept in the understanding of metastatic progression and may indicate the existence of late metastatic seeding. They also underscore the importance of prompt treatment. Validation in independent cohorts is recommended. The author(s) have no proprietary or commercial interest in any materials discussed in this article.