What Ophthalmologists Should Know About the 2026 NCCN Uveal Melanoma Guidelines

Uveal melanoma, the most common type of ocular cancer in the U.S., affects approximately five in 1 million adults annually. The rare malignancy has various manifestations, but a structured approach to diagnosis, treatment and surveillance is possible and necessary, says Arun Singh, MD, Director of Ophthalmic Oncology at Cleveland Clinic Cole Eye Institute.

Updated National Comprehensive Cancer Network (NCCN) guidelines, released in 2026, provide a practical framework for managing suspicious lesions in the choroid and ciliary body and for tailoring follow-up based on metastatic risk.

“The value of the NCCN guidelines is that they are continuously updated to reflect emerging evidence and practical clinical experience,” says Dr. Singh, who presented the uveal melanoma recommendations at the 2026 NCCN Annual Conference.

While the complete document provides detailed flowcharts that guide clinical decision-making as well as full references supporting the recommendations, Dr. Singh says the points highlighted below are most relevant to ophthalmologists.

Initial evaluation of a suspicious lesion

When a patient presents with a suspicious choroidal or ciliary body lesion, with or without visual symptoms, the recommended workup includes:

• Detailed medical history, including personal and family history of malignancy
• Comprehensive ophthalmic examination, including dilated fundus exam and visual acuity assessment
• Tumor characterization, including basal dimensions, thickness and location
• Diagnostic imaging, such as ocular ultrasound, OCT or fluorescein angiography
• Biopsy, if needed to establish diagnosis

For small indeterminate lesions, close observation is appropriate. Reassessment is typically recommended every two to six months initially, then annually if stable. Features that increase concern for melanoma include:

• Growth of the lesion
• Vision loss or other symptoms
• Subretinal fluid
• Tumor margin within 3 mm of the optic disk

Once a lesion is clinically diagnosed as uveal melanoma, additional evaluation should include:

• Ocular imaging and biopsy (for prognosis), if not already performed
• Assessment for ciliary body involvement and extraocular extension
• Systemic imaging to check for metastatic disease

Primary treatment is guided by tumor size

Primary treatment selection depends largely on tumor dimensions, although location, extraocular extension, visual potential and patient preference also are factors.

Small tumors

For tumors 5-19 mm in diameter and less than 2.5 mm thick, treatment options include:

• Observation with close follow-up (when diagnosis is uncertain)
• Plaque brachytherapy
• Particle beam radiation, depending on extraocular involvement and proximity to the optic nerve
• Laser treatment or enucleation when radiation is not possible
• Surgical excision (for small ciliary body tumors)

Medium tumors

For tumors 19 mm or less in diameter and 2.5-10 mm thick, treatment options include:

• Plaque brachytherapy
• Particle beam radiation
• Enucleation, especially for tumors involving more than 50% of the globe or associated with neovascular glaucoma or ocular pain

Large tumors

For tumors more than 19 mm in diameter, more than 10 mm thick, or more than 8 mm thick involving the optic nerve, treatment options may include:

• Radiation therapy
• Enucleation

“These are not the only treatment options,” Dr. Singh notes. “Management must be individualized. In selected patients, observation or enrollment in a clinical trial may be the most appropriate course.”

Surveillance is guided by risk

The new guidelines also introduce a novel approach to metastatic risk stratification and surveillance.

“All uveal melanomas are not the same,” Dr. Singh says. “We must monitor them differently depending on their size and molecular profile.”

Low risk

Tumors with low risk of distant metastasis include T1 lesions and those with favorable molecular features, such as:

• Class 1A or Class 1 PRAME (Preferentially Expressed Antigen in Melanoma)-negative profile
• Disomy 3 (having two copies of chromosome 3)
• Chromosome 6p gain
• EIF1AX mutation

Intermediate risk

Tumors with intermediate risk of distant metastasis include T2 and T3 lesions and those with one or more of these molecular features:

• Class 1B or Class 1 PRAME-positive profile
• SF3B1 mutation

High risk

Tumors with high risk of distant metastasis include T4 lesions and those with one or more of these molecular features:

• Class 2 PRAME-positive profile
• Monosomy 3 (having only one copy of chromosome 3)
• Chromosome 8q gain
• BAP1 mutation

Recommended surveillance (e.g., contrast-enhanced MRI, CT abdomen and pelvis, abdominal ultrasound, CT chest, chest X-ray) varies by risk level:

• Low risk: Every 12 months for 5 years
• Intermediate risk: Every 6-12 months for 10 years
• High risk: Every 3-6 months for 5 years, then every 6-12 months through year 10

“Metastases mostly occur in the liver, but they also can involve the lungs, bone, skin and other soft tissues,” Dr. Singh says. “As preventive and metastasis-directed therapies evolve, identifying which patients need closer surveillance will become even more important.”

Bottom line for ophthalmologists

Following the NCCN guidelines offers several benefits for both patients and clinicians, notes Dr. Singh.

“As ophthalmologists, we want to provide care that is grounded in the best available evidence,” he says. “The guidelines help us do that by offering expert-driven recommendations that standardize care, facilitate access to treatment and give patients resources that empower them to participate in their care.”