The Collaborative Ocular Melanoma Study: An Overview

Curtis E. Margo, MD, MPH


Cancer Control. 2004;11(5) 

In This Article

Abstract and Introduction

Background: The Collaborative Ocular Melanoma Study (COMS) is a 3-arm study that includes two multicenter randomized clinical trials designed to compare the effectiveness of brachytherapy to enucleation for treatment of medium-size choroidal melanomas, and the effectiveness of enucleation with and without preoperative external-beam radiotherapy for large choroidal melanomas. The third arm is an observational study of small choroidal melanomas. Patient accrual ran from 1987 to 1998.
Methods: A review of COMS published reports was conducted.
Results: There is no difference in 5-year all-cause mortality for large- and medium-size choroidal melanomas with COMS-designated treatments. Preoperative radiation for large choroidal melanomas does not improve survival. The accuracy of the clinical diagnosis of choroidal melanoma is excellent.
Conclusions: Data from the trials are still being collected and analyzed, but primary outcomes will unlikely change significantly in the future. Similar rates of mortality after treatment with enucleation and brachytherapy shift the emphasis of selection of therapy to secondary outcomes such as preservation of vision. The findings highlight the need to better understand the biological mechanisms and timing of hematogenous dissemination to achieve an appreciable impact on choroidal melanoma survival.

Melanoma of the choroid is an uncommon malignancy, occurring in approximately 6 individuals per million population annually, or approximately 1,400 new cases in the United States each year.[1] The incidence of choroidal melanoma is about one tenth that of cutaneous melanoma, but unlike skin melanoma, its incidence has remained fairly stable.[2,3] The mean age at diagnosis is the mid 50s.[1] Choroidal melanomas are rare among non-whites.[4,5] Other than an infrequent report of family cluster, choroidal melanoma occurs sporadically. The role of sunlight and other environmental factors in the pathogenesis of uveal melanoma remains unknown.

Enucleation has been the standard of care for the treatment of choroidal melanoma since the latter part of the 19th century. However, the effectiveness of surgical removal of the eye to improve survival has not been unequivocally demonstrated because the natural history of uveal melanoma has never been documented.[6] Most early published series on the treatment of choroidal melanoma by enucleation were small, of poor quality, or noncomparable; thus, the potential benefit of treatment has been difficult to assess.[7] A meta-analysis of 76 published reports of all-cause mortality of patients with choroidal melanoma treated by enucleation from 1966 through 1988 found only eight studies suitable for data extraction.[8] The meta-analysis confirmed that tumor size correlated strongly with survival and provided the best estimates to date for all-cause mortality following enucleation. Classification of tumor size varied among studies with some overlap ( Table 1 ). The combined weighted estimates from these eight studies for 5-year mortality were 16% for small tumors (95% CI, 14% to 18%), 32% for medium tumors (CI, 29% to 34%), and 53% for large tumors (95% CI, 50% to 56%).[8]

Few long-term studies of uveal melanoma are available. A study from the Helsinki University Central Hospital looked at the long-term prognosis of patients treated by enucleation between 1962 and 1981.[9] The study adapted the standardized definitions for coding the cause of death used by the Collaborative Ocular Melanoma Study (COMS).[10] The accuracy of previous biopsy and autopsy material was verified by histopathologic review. Tumor size was considered a continuous variable for regression analysis. Death was attributable to melanoma in 145 (61%) of the 239 patient deaths.[9] The 5-year, 15-year, 25-year, and 35-year uveal melanoma-related mortality rates were 31% (95% CI, 26% to 37%), 45% (95% CI, 40% to 51%), 49% (95% CI, 43% to 55%), and 52% (95% CI, 45% to 58%), respectively ( Table 2 ). These mortality data reflect a substantial proportion of patients dying of metastatic disease 5 or more years after treatment, and they underscore the importance for long-term follow-up in any treatment trial for choroidal melanoma.

The desire to improve survival and preserve vision in patients with choroidal melanoma stimulated the development of alternative therapies. Most popular among these was brachytherapy using radioactive plaques.[11,12,13,14,15] Despite considerable data from clinical series on the effectiveness of radiotherapy, no randomized clinical trial was conducted to compare tumor-related mortality of radiotherapy with enucleation. By the 1980s, there was conflicting evidence to suggest that enucleation hastens tumor-related mortality,[6] that radioactive plaque brachytherapy incurs worse survival than enucleation,[16] and that radioactive brachytherapy was as effective as enucleation in preserving life.[11,14,17]

In 1985, a multicenter randomized clinical trial (COMS) comparing radiation to enucleation was funded by the National Eye Institute to help resolve the dilemma over the selection of therapy. This article reviews specific aspects of the design, execution, and results of the COMS as they pertain to primary and secondary outcomes.


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