Delays between Uveal Melanoma Diagnosis and Treatment Increase the Risk of Metastatic Death
Gustav Stålhammar
Abstract
PurposeTo investigate if the interval between diagnosis and treatment of posterior uveal melanoma is associated with metastatic death.DesignRetrospective, single-center cohort study.Subjects1145 patients consecutively diagnosed with posterior uveal melanoma at St. Erik Eye Hospital, Stockholm, 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.MethodsData on the interval between diagnosis and treatment were collected for all patients. Its prognostic importance was examined with uni- and multivariate competing risks regressions, and with cumulative incidence analyses.Main Outcome MeasuresIncidence of metastatic death (UM mortality) for patients with prompt (<one month from diagnosis) vs. delayed treatment (≥one month), and subdistribution hazard ratios (exp(βj)) for every additional 10-day delay in treatment.ResultsThe mean interval between diagnosis and treatment was 34 days (SD 56, range 0–932). Patients treated promptly had larger tumors, but there were no differences in patient age at diagnosis, tumor distance to the optic disc, in rates of ciliary body involvement (CIB) or extraocular extension (EXE), or in symptom duration before diagnosis. Those who were treated more than a month after diagnosis had greater UM mortality in American Joint Committee on Cancer (AJCC) stage II and III. In stage I, the 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, CIB 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.ConclusionsIncreasing time between diagnosis and treatment of uveal melanoma 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.