Collaborative Ocular Melanoma Study: Results and Lessons

The Collaborative Ocular Melanoma Study (COMS) is the largest trial ever done in uveal melanoma.

It changed how doctors treat the disease.

It showed that eye-sparing radiation gives the same survival as enucleation for medium tumors, so most patients could keep the eye (see choroidal melanoma and plaque brachytherapy).

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Design of the Collaborative Ocular Melanoma Study

The program included three studies, by tumor size.

• Small tumors: an observational study of tumors followed without treatment
• Medium tumors: 1,317 patients with tumors 2.5 to 10 millimeters thick and up to 16 millimeters wide, randomized to iodine-125 plaque or enucleation
• Large tumors: 1,003 patients with tumors over 10 millimeters thick or 16 millimeters wide, randomized to enucleation alone or with external beam radiation before surgery

Collaborative Ocular Melanoma Study: Results in Medium Tumors

Survival was the same: the twelve-year all-cause mortality was about 43 percent in the plaque group and 41 percent in the enucleation group (see the references).

Melanoma-related deaths, likewise, were about 17 percent at twelve years in both arms.

The conclusion was that plaque therapy can also replace enucleation without a loss of survival.

Collaborative Ocular Melanoma Study: Vision After Plaque

Many eyes lost vision after radiation, from radiation retinopathy and optic neuropathy, and about half had a marked drop in acuity within a few years, though the eye was kept in most.

Tumors close to the disc or macula, however, carried the highest risk.

Collaborative Ocular Melanoma Study: Results in Large Tumors

Pre-enucleation radiation did not improve survival, with five-year mortality about 57 percent with radiation and 62 percent without, a difference that was not significant (see the references).

Also, enucleation remains an option for large tumors, and clinicians may offer plaque or proton beam therapy for some.

Small Tumors

The observational study found that small tumors that were watched grew in a significant share of cases.

Some patients died of metastasis (see the references).

It helped to define the risk factors for growth, such as thickness, orange pigment, and symptoms (see choroidal nevus versus small melanoma).

Collaborative Ocular Melanoma Study: Prognostic Factors

Tumor size, extension through the sclera, ciliary body involvement, and age predicted survival, and later work added cytogenetics such as monosomy 3 and gene expression profile.

Impact on Practice

• Plaque brachytherapy became the standard for most medium tumors
• Clinicians told patients that the cure rate is similar with eye-preserving treatment
• Metastatic risk became the focus, so liver imaging surveillance followed

Practical Use

First, discuss the options in terms of survival, vision, and eye retention.

In addition, refer patients to an ocular oncology center for treatment and for systemic surveillance.

An Example Case

A 56-year-old woman has a choroidal melanoma 7 millimeters thick and 12 millimeters wide, 4 millimeters from the disc, with acuity of 20/25.

Following the COMS results, she chooses iodine-125 plaque brachytherapy, and the tumor shrinks over a year, with acuity of 20/60 at two years from radiation maculopathy, which responds to anti-VEGF injections (see radiation retinopathy).

After treatment, she has a liver ultrasound every six months for metastasis surveillance.

How to Explain the Study

Explain that thousands of patients were followed, that treating the tumor with radiation gave the same survival as removing the eye, and that the aim of treatment is to keep the eye and as much vision as possible.

Also, be honest about metastatic risk, which depends on the tumor biology and not on the choice of treatment.

Questions Patients Ask

• Did the treatment spread the cancer? No, the study showed no difference in survival.
• Will I keep my eye? Most patients keep the eye after plaque therapy.
• What is my risk of spread? It depends on the size and the tumor genetics.

What Came After

Since then, proton beam therapy, gene expression profiling, and BAP1 and monosomy 3 testing have given better prognostic information.

Tebentafusp has been shown to extend survival in metastatic uveal melanoma, and trials of adjuvant therapies are also under way.

Key Points to Remember

• Medium tumors: plaque and enucleation gave the same survival
• Large tumors: pre-enucleation radiation did not improve survival
• Small tumors: some grew, so they need close follow-up
• Tumor size and spread predicted survival, while genetics adds to the prognosis

Use in Clinical Practice

Photograph the tumor, measure it by ultrasound, and refer without delay, since early treatment of small tumors gives the best outlook for both the eye and the patient’s life.

In addition, offer genetic counselling and psychological support to patients and families.

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References

1. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol. 2006;124:1684-1693.
2. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of pre-enucleation radiation of large choroidal melanoma II: initial mortality findings. COMS report no. 10. Am J Ophthalmol. 1998;125:779-796.
3. Collaborative Ocular Melanoma Study Group. Mortality in patients with small choroidal melanoma. COMS report no. 4. Arch Ophthalmol. 1997;115:886-893.
4. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 4: Ophthalmic Pathology and Intraocular Tumors. AAO; current edition.