What are the guidelines for melanoma?

From the Guidelines

Melanoma treatment should prioritize neoadjuvant systemic therapies, including pembrolizumab monotherapy, "flip dose" nivolumab, and ipilimumab, for resectable stage III melanoma, as recommended by the NCCN Guidelines for Cutaneous Melanoma, version 2.2024 1.

Key Recommendations

• Neoadjuvant therapy is preferred over the previous standard approach of therapeutic lymph node dissection (TLND) followed by adjuvant systemic treatment for resectable stage III melanoma 1.
• Pembrolizumab monotherapy, "flip dose" nivolumab, and ipilimumab are recommended as neoadjuvant therapy options for resectable stage III melanoma 1.
• Nivolumab and relatlimab combination therapy is also recommended as a neoadjuvant option, with a high pathologic complete response rate and low toxicity 1.

Treatment Considerations

• Early melanomas typically require surgical excision with appropriate margins (0.5-2cm based on tumor thickness) 1.
• Advanced cases may need lymph node evaluation, immunotherapy (pembrolizumab, nivolumab), targeted therapy (for BRAF mutations: dabrafenib/trametinib), or radiation 1.
• Follow-up schedules vary by stage, ranging from every 3-6 months for 2 years then annually for early stages, to more frequent monitoring for advanced disease 1.

Prevention and Detection

• Regular skin self-examinations and annual professional skin checks are essential for early detection 1.
• Prevention measures include applying broad-spectrum sunscreen (SPF 30+) every 2 hours when outdoors, wearing protective clothing, seeking shade, and avoiding tanning beds 1.
• The ABCDE rule (Asymmetry, Border irregularity, Color variation, Diameter larger than 6mm, and Evolution or change over time) can help identify suspicious moles 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Melanoma KEYTRUDA® is indicated for the treatment of patients with unresectable or metastatic melanoma. KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.

The guidelines for melanoma treatment with KEYTRUDA are:

• Treatment of patients with unresectable or metastatic melanoma.
• Adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.

Additionally, YERVOY is indicated for:

• Adjuvant treatment of adult patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy 2.
• Unresectable or Metastatic Melanoma: YERVOY 3 mg/kg every 3 weeks for a maximum of 4 doses 2.
• Adjuvant Treatment of Melanoma: YERVOY 3 mg/kg every 3 weeks for 4 doses, followed by 3 mg/kg every 12 weeks for up to 4 additional doses 2.

From the Research

Diagnosis and Treatment

• The diagnosis of melanoma is multidisciplinary and begins by obtaining an accurate diagnosis through examination of the lesion and surrounding areas, and an excisional biopsy 3
• The treatment of melanoma is guided by the pathology results, and may include laboratory studies and imaging for staging and surveillance 3
• The recommended margins of excision have become more conservative, and lymphoscintigraphy and sentinel node biopsy have replaced elective node dissections 4

Staging and Prognosis

• Staging is based on depth of invasion, mitotic rate, and spread into lymph nodes and other sites 5
• The new staging system for melanoma recognizes that patients with only microscopic metastatic nodal disease fare better than patients with clinically enlarged metastatic nodes, and that it is the number of nodes involved with metastases, not their size, that determines the patient's prognosis 4
• Ulceration is second only to Breslow's thickness in the new staging system, and in transit (satellite) lesions have also been included 4

Adjuvant Therapy

• Adjuvant therapy options for high-risk melanoma include high-dose interferon-α, immune checkpoint inhibitors, targeted therapy, radiotherapy, and chemotherapy 6
• The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma 6
• Pembrolizumab and nivolumab have obtained regulatory approval or are under review for the treatment of resected stage IIB-IIC melanoma 6

Surveillance and Follow-up

• Patient surveillance is performed to assess treatment results and detect recurrences amenable to further treatment 7
• Strategies based on evidence are required to accurately stage and effectively follow patients with melanoma, and staging and surveillance require careful use of resources to be cost effective 7