Guideline sources The following summarized guidelines for the evaluation and management of uveal melanoma are prepared by our editorial team based on guidelines from the American Society of Clinical Oncology (ASCO 2022), the Uveal Melanoma Consensus Group (UM-CG 2016), and the United Kingdom National Multidisciplinary Guidelines (UKNMG 2015). 1 2 3 Calculator Calculator TNM classification for ciliary bo TNM classification for iris melan Guidelines 1. Diagnostic investigations Initial assessment: As per UM-CG 2016 guidelines: https://web.pathway.md/diseases/recQMfWwiXLgQKDH7 1/5 6/29/23, 3:49 AM Uveal melanoma Pathway Evaluate all intraocular malignancies and indeterminate lesions by a provider trained in all aspects of care (medical, oncologic, surgical, radiotherapy, and laser therapy) to determine the appropriate treatment, as observation with the subsequent delay in therapy (even in small intraocular malignancies with 2 mm thickness) can increase the risk of metastasis. E Obtain a complete ophthalmologic assessment of risk factors for future growth in patients with indeterminate lesions. Discuss with the patient about treatment, including the future risk of growth and metastasis balanced with the risk of visual loss from treatment, in the presence of risk factors. E As per UKNMG 2015 guidelines: Obtain ophthalmoscopy, fundus photography, and conventional ocular ultrasound for the diagnosis of uveal melanoma. A Obtain ultrasound biomicroscopy or anterior segment optical coherence tomography for the diagnosis of ciliary body melanoma. B Imaging for staging: As per UM-CG 2016 guidelines, obtain any of the following imaging schemes to rule out metastases of uveal melanoma: CT of chest and abdomen (liver protocol for abdomen) whole-body positron emission tomography-CT liver MRI and chest CT. E As per UKNMG 2015 guidelines, obtain CT or positron emission tomography-CT for whole- body staging (chest, abdomen, and pelvis). B Show 4 more Laboratory tests: obtain CBC and LFTs in the evaluation of metastases of uveal melanoma. E 2. Diagnostic procedures Biopsy: Consider performing a diagnostic biopsy if the clinical diagnosis is uncertain following noninvasive techniques. C Consider performing FNA biopsy either with a direct transscleral or transvitreal approach. C 3. Medical management Expectant management: do not offer observation in patients with uveal melanoma except in unique situations. D Systemic therapy: As per ASCO 2022 guidelines: Offer tebentafusp in previously untreated HLA-A02:01-positive patients with metastatic uveal melanoma. B https://web.pathway.md/diseases/recQMfWwiXLgQKDH7 2/5 6/29/23, 3:49 AM Uveal melanoma Pathway Insufficient evidence to recommend for or against any specific systemic therapy in all other patients with uveal melanoma. Offer enrollment in clinical trials where possible. I As per UM-CG 2016 guidelines, insufficient evidence to support the use of adjuvant systemic therapy in high-risk patients (monosomy 3, gene-expression profiling class 2, or tumors > 10 mm thick) and in patients with metastases. Consider offering enrollment in clinical trials. I As per UKNMG 2015 guidelines: Consider offering patients enrollment for clinical trials wherever possible and inform them about available trial options. C Offer systemic treatment in specialist centers with appropriate oncology expertise in uveal melanoma in patients with good performance status (performance status 0-2) declining trials or when suitable clinical trials are unavailable. B 4. Therapeutic procedures Brachytherapy: As per UM-CG 2016 guidelines, offer brachytherapy in patients with high-risk indeterminate lesions and lesions < 10 mm in thickness and 18 mm in maximum diameter. E Show 2 more As per UKNMG 2015 guidelines, offer brachytherapy ruthenium-106 or iodine-125 in patients with small/medium/large uveal melanoma (< 20 mm in basal diameter). A Show 2 more Transpupillary thermotherapy: As per UM-CG 2016 guidelines: Do not offer transpupillary thermotherapy as a primary therapy in patients with uveal melanoma because of a relatively high rate of local recurrence. D Consider offering transpupillary thermotherapy as an adjunct treatment in selected patients with choroidal melanoma to reduce the risk of local recurrence after radiotherapy or as a primary treatment for medium-risk nevi. E As per UKNMG 2015 guidelines: Consider offering transpupillary thermotherapy for local recurrence and as adjuvant therapy in patients with uveal melanoma. C Consider offering photodynamic therapy in patients with small melanoma. C 5. Surgical interventions Indications for surgery: As per UM-CG 2016 guidelines: Reserve enucleation for lesions > 10 mm in thickness or 18 mm in diameter (or both) because of complications secondary to radiation, including the risk of severe vision loss and loss of the eye. E Consider performing excision (iridocyclectomy and iridectomy) for selected ciliary body and iris lesions. E https://web.pathway.md/diseases/recQMfWwiXLgQKDH7 3/5 6/29/23, 3:49 AM Uveal melanoma Pathway As per UKNMG 2015 guidelines, consider performing exoresection with or without plaque brachytherapy in patients with medium-to-large melanoma with narrow basal diameter. C Show 3 more Resection of metastases: As per UM-CG 2016 guidelines: Consider performing surgical resection of potentially resectable liver metastasis in highly selected patients. Recognize that most patients with metastatic disease will present with diffuse involvement of the liver and, therefore, will not qualify for surgical resection. E Insufficient to recommend on the role of ablative techniques in the setting of uveal melanoma metastatic to the liver. E As per UKNMG 2015 guidelines, consider offering regional therapy in patients with liver- predominant disease. C Show 5 more 6. Patient education General counseling: Discuss all available procedural and treatment options with the patient, including their risks, benefits, and impact on quality of life. B Inform patients that there is no proven survival advantage between any of the offered modalities. A 7. Follow-up and surveillance Follow-up: As per UM-CG 2016 guidelines: Obtain an annual liver ultrasound and perform a physical examination indefinitely in low- risk patients (gene-expression profiling class 1a or 1b, no monosomy 3 detected, or tumor < 9 mm thick and no genetic assessment). Consider transitioning follow-up to the family physician at 5 years. E Perform an annual physical examination indefinitely and obtain imaging every 6 months (consisting of liver ultrasound alternating with abdominal or liver MRI; consider obtaining other modalities if the body habitus limits ultrasound) for 10 years in high-risk patients (gene-expression profiling class 2, monosomy 3 detected, or tumor 9 mm thick and no genetic assessment). Consider transitioning follow-up to the family physician at 5-10 years. E As per UKNMG 2015 guidelines, obtain surveillance by a specialist multidisciplinary team incorporating expertise from ophthalmology, radiology, oncology, cancer nursing, and hepatic services. B Show 4 more Clinical findings https://web.pathway.md/diseases/recQMfWwiXLgQKDH7 4/5 6/29/23, 3:49 AM Uveal melanoma Pathway Symptoms Past medical history Blurred vision Choroidal nevus Eye pain Cutaneous melanoma Flashing lights Dermal melanocytosis Floaters and flashes Dysplastic nevus syndrome Vision loss Liver metastasis Visual disturbances Lung cancer Meningioma Neurological exam Neurofibromatosis type 1 Visual field defect Ocular exam Integument exam Conjunctivitis Hyphema Fitzpatrick skin type 1 Iris discoloration Iris mass Retinal detachment Retinal lesions Uveitis Genetic testing Brca1 gene mutation References 1. P Nathan, V Cohen, S Coupland et al. Uveal Melanoma UK National Guidelines. Eur J Cancer. 2015 Nov;51 16 2404 12. Open 2. E Weis, T G Salopek, J G McKinnon et al. Management of uveal melanoma: a consensus-based provincial clinical practice guideline. Curr Oncol. 2016 Feb;23 1):e57 64. Open 3. Rahul Seth, Hans Messersmith, Pauline Funchain et al. Systemic Therapy for Melanoma: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2022 Jul 20;40 21 2375 2377. Open 4. David E Elder, Boris C Bastian, Ian A Cree et al. The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway. Arch Pathol Lab Med. 2020 Apr;144 4 500 522. Open https://web.pathway.md/diseases/recQMfWwiXLgQKDH7 5/5