Oncology

The Collaborative Ocular Melanoma Study (COMS) 

Objective: The COMS trial sought to determine the superior treatment for choroidal melanomas, comparing the previous standard of care, enucleation, to brachytherapy using radioactive plaques. Prior to the COMS trial, the majority studies investigating the effectiveness of enucleation for decreasing mortality in choroidal melanoma patients only reported short-term data and were non-comparable. Plaque-based brachytherapy introduced a potentially more effective treatment option, but it had not yet been directly compared to enucleation in a clinical trial.  

Design:   

This was a three-arm study incorporating two multicenter randomized clinical trials: 

• 1,003 patients with large choroidal melanomas (defined as >8 mm in thickness and/or >16 mm in longest base diameter) were randomized to enucleation alone or enucleation preceded by external-beam radiation (20 Gy) 

• 1317 patients with medium melanomas (defined as 3.1-8 mm in thickness and no more than 16 mm in longest base diameter) were randomized to enucleation or brachytherapy using iodine-125.  

• Patients with small choroidal melanomas (1-3 mm in apical thickness and at least 5 mm in diameter) were enrolled in a registry and followed clinically 

A Mortality Coding Committee used autopsy with histopathologic confirmation of melanoma metastasis at time of death and antemortem imaging studies of suspected metastasis (with and without histopathologic confirmation) to confirm whether death was related to the underlying choroidal melanoma.  

Inclusion criteria:  

1. Unilateral choroidal melanoma that is from 2.5-10 mm in apical height and no more than 16 mm in longest basal diameter 

2. Judged by examining oncologist or internist to be free of metastatic melanoma and other primary or metastatic cancers 

3. Best corrected visual acuity of 20/200 or better in the fellow eye 

Exclusion criteria:   

1. Patients with coexisting disease that could compromise survival 

2. Patients with tumor contiguous to the optic disc 

3. Treatment with immunosuppressive therapy 

4. History of noninvasive nonmelanotic skin cancer or carcinoma in situ of the uterine cervix 

5. Previous treatment for choroidal or ciliary body melanoma in either eye 

6. Treatment of any condition secondary to the tumor 

7. Fine needle biopsy of the melanoma 

8. Extrascleral tumor extension 2.0 mm or thicker detected during echography or clinical examination 

9. Diffuse, ring, or multifocal tumors 

Primary Outcome:  

1. Time to death from all-cause mortality 

Secondary Outcome:  

• Metastasis-free survival 

• Cancer-free survival 

• Years of useful vision 

Results 

1. In the large choroidal melanoma trial: Patients receiving preoperative radiation had no statistically significant difference in 5-year survival. The 5-year melanoma related mortality rate was 27%.  There were fewer biopsy confirmed tumor recurrences of the orbit in patients receiving prenucleation radiation (p=0.03).  

2. In the medium-size melanoma trial, 660 patients were assigned to enucleation and 657 to brachytherapy. 188 patients assigned to enucleation and 176 patients assigned to brachytherapy died. The 5-year cumulative mortality rates were 19% for enucleation and 18% for brachytherapy. There was no statistically significant difference in the unadjusted or adjusted mortality rates.  

1. The Mortality Coding Committee classified 345 of the 264 deaths from all causes. 101 patients from each group had metastatic melanoma confirmed or suspected at death 

3. In eyes treated with brachytherapy, there was a quadrupling of the minimum angle of resolution, or loss of 6 or more lines of VA from baseline in 18% of the patients by 1 year, 34% by 2 years, and 49% by 3 years.  

4. 42 patients with medium-size melanoma deferred treatment and enrolled in a natural history study. The estimated 5-year melanoma mortality rate in this group was 30% 

5. In the small choroidal melanoma group, there were 204 patients enrolled and the median length of follow up was 92 months. 8 patients opted for treatment at the time of enrollment, and 67 decided on treatment during follow up 

1. 27 patients died, but only 6 deaths were attributed to metastatic melanoma. 4 of these 6 deaths occurred more than 5 years after enrollment 

2. Estimated 5-year all-cause mortality rate was 6%, and 8-year mortality rate was 14.9% 

3. 5-year and 8-year tumor specific mortality rates were 1% and 3.5% respectively  

Take Home Points 

• There was no significant difference in 5-year all-cause mortality for large and medium sized choroidal melanomas 

• Pre-operative radiation for large choroidal melanomas had no significant effect on survival  

• For small choroidal melanomas, observation alone is safe 

• Patients treated with brachytherapy experience significant vision loss