Routes of Extraocular Extension of Uveal Melanoma: Risk Factors and Influence on Survival Probability

Abstract

To correlate extraocular spread with other survival predictors and with metastatic death and determine whether there was any relationship between the size of the extraocular tumor and survival. Nonrandomized retrospective case series. Eight hundred forty-seven patients with uveal melanoma treated by primary enucleation between January 1993 and December 2006. Baseline variables were age, gender, largest basal tumor dimension, tumor height, anterior tumor margin, route of extraocular spread (i.e., aqueous channels, vortex veins, ciliary arteries, or ciliary nerves), tumor cell type, mitotic rate, closed connective tissue loops, and monosomy 3. Determination of death was based on the National Health Service Cancer Registry. Prevalence and route of extraocular extension and correlation with intraocular tumor characteristics and metastatic death. The 847 patients had a mean age of 64 years. Extraocular tumor extension was recorded in 124 patients and occurred via aqueous channels (37, 29.8%); ciliary arteries (34, 27.4%); vortex veins (28, 18.5%); ciliary nerves (11, 8.9%); optic nerve (1, 0.8%), and a variety of rare combinations of these routes (13, 10.4%). Extraocular spread via aqueous channels occurred in 15.2% of tumors involving ciliary body or angle, but through other channels in <6% tumors at risk. Extraocular spread correlated with anterior tumor extension, large basal tumor diameter, epithelioid cellularity, closed loops, high mitotic rate, and monosomy 3. Extraocular spread along aqueous drainage channels correlated inversely with intraocular tumor dimensions. Venous spread correlated with large basal tumor diameter. Arterial spread correlated with location near optic disc. Neural spread correlated weakly with mitotic rate. Log rank analysis showed metastatic death to correlate with extraocular extension, irrespective of the route. Multivariate Cox analysis showed the correlation between metastatic death and extraocular spread to be weaker than with largest basal tumor diameter, closed loops, epithelioid cells, and mitotic rate. Size of extraocular tumor was not significant (P = 0.3). Extraocular spread correlated with increased mortality because it was associated with increased tumor malignancy and, in the case of posterior tumors, more advanced disease. Type of scleral route and size of extraocular tumor were unimportant regarding risk of systemic dissemination and tumor-related death.