Intraocular Tumor Update: Management of Uveal Melanoma
The COMS and ongoing research offer guidance among the numerous available therapeutic options.
By William F. Mieler, MD
When a patient presents with a uveal melanoma, we often rely on the results of the Collaborative Ocular Melanoma Study (COMS) to guide our patients with their treatment regimen. In addition to the COMS, we also have a number of therapeutic options: We can observe the tumor, remove the eye, employ laser, use brachytherapy or charged-particle radiation, locally resect the tumor, or use hyperthermia in combination with brachytherapy. So what's the best treatment for the patient?
Factors such as the size and extent of the tumor, its location in the eye, tumor activity, status of the fellow eye, the patient's age, and the overall prognosis for life all go into our decision. But it's also essential for us to know and apply the results of the latest research to optimize the patient's outcome.
In particular, I'll focus on the results of the COMS.
The COMS was a large multicenter clinical trial, which was started in 1985 and completed patient recruitment several years ago. The trial looked at more than 8,700 patients with small, medium and large tumors. The results were insightful for each tumor group.
Small tumors. The small tumor trial of 204 patients was a non-randomized pilot study looking at the rate of tumor growth. Researchers looked at factors predictive of tumor growth, as well as the incidence of all-cause and melanoma-specific mortality.
They found that at 2 years, tumors in one in five patients showed signs of growth, compared to one-third at 5 years. The main risk factor for growth was a larger tumor to start, along with the presence of orange pigmentation, absence of drusen, absence of pigmentary changes, and close apposition to the optic nerve.
Even among patients whose tumors grew, the all-cause mortality rate was very low: 6% at 5 years and 15% at 8 years. But most importantly, the melanoma-specific mortality rate was only 1% at 5 years and 4% at 8 years after entry into the study.
This observational trial stopped recruiting patients after 4 years because researchers wanted to focus on the main part of the trial, the medium tumor trial. Still, in spite of that, the follow-up data has proved valuable in helping ophthalmologists predict which specific tumors have a greater chance of eventual growth. As a result, the tendency is to treat many of these tumors as a smaller stage.
Medium tumors. The medium tumor trial compared brachytherapy with enucleation in 1,317 patients. The primary result showed that either treatment option offered comparable chances of survival. Of interest, patients who had been randomized to brachytherapy generally lost substantial vision over the course of their follow-up. At 3 years, almost half the patients with brachytherapy lost at least six lines of vision. This begs the question: Is keeping the eye and losing 6 lines of vision that much different than having no eye with enucleation surgery?
The all-cause mortality rate was roughly 20% in both groups, and melanoma-specific mortality was between 9% and 11% -- no statistical difference between the two groups. So which treatment is better, brachytherapy or enucleation? The decision can be left to the discretion of the ophthalmologist, and more importantly, the patient.
Large tumors. The large tumor trial included 1,003 patients. It compared standard enucleation to enucleation preceded by external beam radiation treatment. The result: Pre-enucleation radiation therapy offered no apparent benefit over conventional enucleation surgery and, therefore, should not be employed. For all-cause and melanoma-specific mortality, please see the chart on page 13-S.
CONCLUSIONS FROM THE COMS
Overall, when we look at the COMS study, we conclude that small tumors do grow. They have a one-third chance of growth by 5 years, but most patients do very well. Patients with large tumors have a high rate of mortality, but there is no apparent difference when you employ pre-enucleation radiation therapy compared to standard enucleation. And most significantly, for medium tumors, there is no difference in patient survival following brachytherapy or enucleation surgery.
COMS Study Results
|Medium Tumor Trial (5 years)|
|Large Tumor Trial (5 years/8 years)|
THE LONG VIEW
When we look at any studies regarding treatment for intraocular tumors, it's important to keep in mind that these processes are quite rare, and major strides rarely happen quickly. We really would like to see at least 5 years of follow-up before accepting the true benefit of any type of tumor treatment. Yet, studies often report data of only a year or two. That's why when we get excited about what a new development could do for our patients, we need to note the length of follow-up. It could be revealed -- as with treating some tumors with newer modalities, such as transpupillary thermo-therapy (TTT) as an example -- that early results are much better than those that appear 3 to 5 years later.
While we may not be able to apply the results of the COMS to all of our patients with uveal melanomas, the study does provide excellent long-term data for many of our melanoma patients. Most other treatment modalities do not have as conclusive data on which we can base recommendations.
Dr. Mieler is a professor and chair of the Ophthalmology Department at the University of Chicago.