Collaborative Ocular Melanoma Study (COMS)

• To evaluate therapeutic interventions for patients who have choroidal melanoma, the most common primary eye cancer affecting adults, and to assess the potential life-preserving as well as sight-preserving role of radiation therapy.
• To determine which of two standard treatments, removal of the eye or brachytherapy, is more likely to prolong survival of eligible patients with medium-sized choroidal melanoma.
• To determine whether preoperative radiation prolongs life for patients whose eyes with large choroidal melanoma are enucleated.

For more than 100 years, removal of the eye (enucleation) has been the standard treatment for choroidal melanoma. Before the COMS was initiated in 1986, interest in radiation therapy had increased because of the potential for saving the eye and perhaps some vision. However, the merits of radiation with respect to prolonging patient survival were unknown. The best data from nonrandomized studies suggested that there was no difference in length of remaining life between patients treated with radiation and those whose eyes were enucleated. Thus, it was appropriate and necessary to conduct a randomized, controlled clinical trial in which a large number of patients would be followed for many years in order to compare enucleation and radiation with respect to relative success in prolonging survival of choroidal melanoma patients.

The Collaborative Ocular Melanoma Study (COMS) is a set of long-term, multicenter, randomized controlled trials. In the trial for patients with tumors of medium size, enucleation and irradiation with an iodine-125 episcleral plaque are compared on the basis of length of remaining life. All randomized patients will be followed for 5 to 15 years or until death. For patients randomly assigned to enucleation, the eye was removed following a standard procedure. For patients assigned to plaque irradiation, the margins of the tumor were located and the dimensions of the tumor were measured by the ophthalmic surgeon. A gold plaque with a plastic seed carrier that contained the proper dosage and configuration of radioactive iodine seeds was sutured to the outside (sclera) of the eye over the base of the tumor. This procedure made possible the delivery of a high dose of radiation to a very localized area (85 Gy [TG-43] to the tumor apex). The plaque typically was removed from the eye after three to seven days. Enrollment was completed in this trial in July 1998 with 1,317 patients enrolled. Clinical follow-up of patients will end in July 2003.

In the COMS trial of preoperative radiation, patients with large tumors were randomized to enucleation alone or to enucleation preceded by 20 Gy of external beam radiation. The two randomly assigned groups of patients were followed for at least five years or until death and have been compared on the basis of length of remaining life and other outcomes. Enrollment in this trial was completed in December 1994, with 1,003 patients enrolled. Clinical follow-up of all patients in this trial ended in July 2000.

Accrual to a nonrandomized pilot study to assess the feasibility of a randomized trial for small tumors was halted in 1989. Additional followup of those 204 patients was carried out from 1994 to 1996.

The COMS is conducted in 43 clinical centers located in major population areas of the United States and Canada. Six resource centers participate and have major roles in quality assurance for the study. Information gathered and analyzed includes time to death from all causes, time to death from cancer (whether metastatic choroidal melanoma or not), diagnosis of other tumors, complications of radiation, and changes in visual acuity. A parallel study of quality of life for patients enrolled in the trial of radioactive plaque was initiated in January 1995. From November 1986 through July 1998, 8,712 patients with choroidal melanoma of all sizes were screened for eligibility for a COMS clinical trial.

Men and women eligible for the study had to be age 21 or older, have primary choroidal melanoma in only one eye, and have no evidence of metastatic disease. Accurate estimation of tumor thickness by echography also was required.

No longer recruiting. Comments: Recruitment began in November 1986. Accrual to the trial of pre-enucleation radiation (large tumor trial) was completed on December 15, 1994, when the sample size goal was met; 1,003 patients enrolled. Accrual to the trial of radioactive plaque (medium tumor trial) was completed on July 31, 1998, when 1,317 patients had enrolled.

Ongoing. Comments: Patient follow-up ongoing in the trial of radioactive plaque.

Nonrandomized Small Tumor Pilot Study
The treatment and mortality results of the COMS nonrandomized small tumor pilot study were reported in 1997. From December 1986 to August 1989, 204 patients with small choroidal melanoma, defined as 1.0 to 3.0 mm in apical height and at least 5.0 mm in basal diameter, were enrolled in a prospective followup study. The median length of followup was 92 months. Eight percent of patients were treated at the time of study enrollment and an additional 33 percent were treated during followup. Based on 27 deaths, the Kaplan-Meier estimate of five-year all-cause mortality was 6.0 percent (95 percent confidence interval, 2.7 percent - 9.3 percent) and eight-year all-cause mortality was 14.9 percent (95 percent confidence interval, 9.6 percent - 20.2 percent). Mortality findings and analysis of predictors of growth have been published (COMS Reports Nos. 4 and 5).
The Randomized Trial of Pre-Enucleation Radiation for Large Choroidal Melanoma
Initial mortality findings published in 1998 (COMS Report No. 10) showed that patients with large choroidal melanoma had similar survival rates regardless of whether they were treated with radiation prior to removal of the eye or had their eye removed without prior radiation therapy. Five-year survival rates were approximately 60 percent in both treatment arms. The COMS large tumor trial found neither benefit nor harm from treating ocular melanoma patients with radiation before removal of the eye. However, patients who had pre-enucleation radiation had fewer local complications (COMS Report No. 11).
The Randomized Trial of I-125 Brachytherapy for Medium Choroidal Melanoma
Initial mortality findings published in 2001 (COMS Report No. 18) showed that survival rates for radiation therapy (I-125 brachytherapy) and enucleation (removal of the eye) are about the same. The five-year survival rate of patients who were treated with either radiation therapy or eye removal was 82 percent, considerably better than the 70 percent five-year survival rate that had been projected when the study was designed in 1985. Compared to immediate loss of vision when the eye is removed, eyes treated with radiation steadily lost vision gradually, with 63 percent having visual acuity of 20/200 or worse by three years after treatment (COMS Report No. 16).