The incidence of metastatic uveal melanoma is as high as 50% at 25 years after treatment for ciliary body or choroidal melanoma. The COMS reported an incidence of metastatic disease of 25% at 5 years after initial treatment and 34% at 10 years. However, metastatic disease at the time of initial presentation is rare and can be detected in fewer than 2% of patients. It is likely that a proportion of patients have undetectable micrometastases at the time of their primary treatment.
The liver is the primary organ involved in metastatic uveal melanoma; in 90% of patients, liver involvement is the first manifestation of metastatic disease. Other relatively frequent sites, generally after liver metastasis, include the lungs, bones, and skin. In cases that were autopsied, liver involvement was found in 100% of patients with metastases and lung involvement in 50%.
All patients benefit from metastatic evaluation before definitive treatment of intraocular melanoma (Table 17-5). The purpose of this evaluation is two-fold:
To determine whether the patient has any other medical conditions that contraindicate surgical treatment or need to be treated. For example, the COMS and smaller studies found a second primary cancer in approximately 10% of patients. If there is any question about whether the lesion in the eye is a metastatic tumor, the clinician should ensure a thorough medical evaluation to determine the site of primary malignancy.
To rule out the possibility of detectable metastatic melanoma from the eye, especially for AJCC T3 melanomas (metastasis found in 3%) and T4 melanomas (metastasis found in 20%). When metastatic disease is clinically present during the pretreatment evaluation, treatment of the primary intraocular tumor will depend on patient and physician preference.
Table 17-4 AJCC Staging of Ciliary Body and Choroidal Melanoma
Table 17-5 Imaging Options for Staging and Surveillance of Metastases in Uveal Melanoma
Initial staging evaluation for uveal melanoma should include a comprehensive physical examination and imaging of the lungs and liver. Chest/abdominal/pelvic CT with intravenous contrast material or, alternatively, MRI of the abdomen with gadolinium contrast or liver ultrasonography together with chest imaging with CT or an x-ray can evaluate the extent of the disease. Liver imaging is the most important component of the staging evaluation. Lung imaging is also usually performed at the time of diagnosis, although its yield is low. A positron-emission tomography (PET) scan typically is not performed for uveal melanoma staging or surveillance because these tumors may not be fluorodeoxyglucose avid; thus, this imaging modality has low sensitivity.
To detect metastatic disease in patients with uveal melanoma at an early phase, serial surveillance imaging is often performed over time. Strategies vary, with some centers imaging only the liver and others recommending imaging both the liver and the lungs. The same imaging modalities used in the initial staging may be used in surveillance imaging, with the recognition that exposure to ionizing radiation (ie, with CT scans) should be minimized. Liver function tests can be considered; however, they lack sensitivity and specificity and are not widely used in the modern era of uveal melanoma management. Possible novel blood markers for early detection of metastatic uveal melanoma are being explored.
In 2018, the first National Comprehensive Cancer Network (NCCN) clinical practice guidelines for uveal melanoma were published. NCCN guidelines recommend that surveillance imaging be considered for 10 years after treatment of the intraocular tumor and then as clinically indicated. Systemic imaging recommendations were stratified on the basis of expected risk of distant metastasis. For patients with a high risk for metastasis (eg, AJCC T4, gene expression profiling class 2), imaging is considered every 3–6 months for 5 years, and then every 6–12 months for 10 years. For patients at medium risk (eg, AJCC T2 and T3, class 1B), imaging is considered every 6–12 months for 10 years. No specific recommendations are made for low-risk patients (eg, AJCC T1, class 1A), and clinical practices vary considerably for this group. Some patients may choose to forgo asymptomatic surveillance imaging because of limited treatment options for advanced uveal melanoma and the anxiety caused by serial imaging.
If a lesion of concern is identified on surveillance imaging, a liver or other organ-site biopsy may confirm metastatic disease. Biopsy is appropriate before initiating treatment for metastatic disease.
The interval between the diagnosis of primary uveal melanoma and metastasis depends on many clinical, histologic, cytogenetic, and molecular genetic factors. It varies from a few months to more than 25 years. When metastatic disease is diagnosed early enough, the options for treatment include surgical resection; chemotherapy, including intraarterial hepatic chemotherapy and chemoembolization; immunotherapy or biological therapy; and hepatic selective internal radiation therapy (SIRT, also known as intrahepatic radioembolization). However, it remains unclear how these therapies affect overall patient survival and quality of life.
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Kujala E, Damato B, Coupland SE, et al. Staging of ciliary body and choroidal melanomas based on anatomic extent. J Clin Oncol. 2013;31(22):2825–2831.
Kujala E, Mäkitie T, Kivelä T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003;44(11):4651–4659.
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NCCN Clinical Practice Guidelines in Oncology: Uveal Melanoma. Version1.2018. March 2018. National Comprehensive Cancer Network website. Accessed February 14, 2020. https://www.nccn.org/professionals/physician_gls/default.aspx
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.