What are the guidelines for Mucosal Melanoma?

From the Guidelines

Mucosal melanoma management should prioritize a multidisciplinary approach, focusing on surgical resection with wide margins when possible, adjuvant radiation therapy, and systemic therapy with immune checkpoint inhibitors or BRAF inhibitors, considering the distinct genetic profiles and poor prognosis of this disease. The treatment of mucosal melanoma is complex due to its rarity and aggressive nature, often requiring individualized care 1. Initial treatment typically involves surgical resection with wide margins when possible, though anatomical constraints in mucosal sites often limit this approach. For localized disease, adjuvant radiation therapy is frequently recommended to reduce local recurrence risk, typically delivered at doses of 50-70 Gy depending on the site 1.

Systemic Therapy Options

Systemic therapy options include:

• Immune checkpoint inhibitors like pembrolizumab (200 mg IV every 3 weeks) or nivolumab (240 mg IV every 2 weeks), which may be used alone or in combination with ipilimumab (1 mg/kg every 6 weeks with nivolumab)
• BRAF inhibitors like dabrafenib (150 mg orally twice daily) plus trametinib (2 mg orally once daily) can be considered for patients with BRAF V600 mutations Regular surveillance is essential, with physical examinations every 3-6 months for the first 2-3 years, then every 6-12 months thereafter, along with imaging studies 1.

Genetic Profiles and Prognosis

Mucosal melanomas have distinct genetic profiles compared to cutaneous melanomas, with higher rates of KIT mutations and lower rates of BRAF mutations, which influences treatment selection 1. The prognosis is generally poor compared to cutaneous melanoma, with 5-year survival rates of approximately 25-30%, emphasizing the importance of early detection and aggressive multimodal treatment 1.

Treatment Considerations

The Expert Panel is aware of nonrandomized data that suggest KIT-positive mucosal melanoma may be responsive to imatinib, but the consensus is that therapies recommended for unresectable and/or metastatic mucosal melanoma are more likely to be beneficial regardless of KIT status 1. The NCCN Guidelines for Melanoma do not include recommendations for the diagnostic workup or treatment of early-stage mucosal or uveal melanoma, but guidelines for initial diagnostic workup and treatment of mucosal melanoma of the head and neck can be found in the NCCN Guidelines for Head and Neck Cancers 1.

From the Research

Treatment Guidelines for Mucosal Melanoma

• Surgical treatment is currently the treatment of choice for localized disease, however, the recurrence rate is common 2
• For advanced or metastatic disease, immunotherapy with PD-1 inhibitors and anti-CTLA is generally first-line treatment, although the overall responses to immunotherapy in MM are often lower and less robust when compared to that observed in cutaneous melanoma 2
• Adoptive-TIL therapy have shown great promise in treating mucosal melanoma 2
• Surgical resection for local control plays a critically important role in the treatment of sinonasal mucosal melanoma regardless of the presence of metastases and whether immunotherapy will be given 3
• Neo-adjuvant systemic immunotherapy with ipilimumab and nivolumab has been shown to be effective in achieving a durable complete response in a patient with a mucosal melanoma of the rectum 4
• Combination immunotherapy (including both nivolumab and ipilimumab) shows greater efficacy than either therapy alone in treating head and neck mucosal melanoma 5
• The therapeutic landscape for mucosal melanoma has evolved substantially in recent years, with new targeted therapy options as well as combination therapies built on the backbone of anti-PD-1/PD-L1 antibodies available 6

Immunotherapy in Mucosal Melanoma

• Immunotherapy may demonstrate efficacy in managing distant disease, but surgery should remain the first-line treatment for the primary site 3
• Ipilimumab and nivolumab combination immunotherapy has been shown to be effective in achieving a partial response in a patient with a mucosal melanoma of the rectum 4
• Nivolumab maintenance therapy has been shown to be effective in achieving a complete response in a patient with a mucosal melanoma of the rectum 4
• Combination immunotherapy (including both nivolumab and ipilimumab) shows greater efficacy than either therapy alone in treating head and neck mucosal melanoma 5

Surgical Treatment in Mucosal Melanoma

• Surgical resection is widely accepted as a critical component for definitive treatment of sinonasal mucosal melanoma 3
• Surgical resection for local control plays a critically important role in the treatment of sinonasal mucosal melanoma regardless of the presence of metastases and whether immunotherapy will be given 3
• Surgical intervention may be required to achieve a tumor-free situation, but neo-adjuvant systemic immunotherapy can be effective in reducing the tumor size and achieving a complete response 4