Treatment of Stage 3 Melanoma

Introduction to Treatment

The National Comprehensive Cancer Network recommends complete surgical resection followed by adjuvant immunotherapy with either nivolumab or pembrolizumab for 52 weeks, with adjuvant radiation therapy strongly considered given the head and neck location 1

Complete lymph node dissection of the involved nodal basin is the standard surgical approach for clinically positive Stage III melanoma, according to the National Comprehensive Cancer Network and the European Society for Medical Oncology 2, 3
The American Joint Committee on Cancer classifies a submandibular mass as regional lymph node metastasis, requiring therapeutic lymph node dissection 4
Wide excision with 1 cm clinical margins is recommended if a primary melanoma site is identified on the head/neck, as per the European Society for Medical Oncology 3
Facial nerve preservation should be attempted unless the nerve is grossly involved or preoperative dysfunction exists, as recommended by the National Comprehensive Cancer Network 4

Adjuvant radiation therapy to the cervical/submandibular nodal basin should be strongly considered in this case, according to the National Comprehensive Cancer Network and the American Society for Radiation Oncology 1, 2, 5
The American Society for Radiation Oncology recommends radiation therapy for high-risk features including multiple positive nodes, large nodes, or macroscopic extranodal extension 2, 5

The American Society of Clinical Oncology recommends adjuvant immunotherapy with anti-PD-1 agents (nivolumab or pembrolizumab) for 52 weeks as the preferred treatment approach 1, 6
Nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks for 52 weeks is a recommended first-line option, with a 12-month recurrence-free survival of 70.5% vs 60.8% with ipilimumab (HR 0.65, P<0.001), as reported by the CheckMate 238 trial 6
Pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks for 52 weeks is another recommended first-line option, with a 12-month recurrence-free survival of 75% vs 61% for placebo (HR 0.57, P<0.001), as reported by the KEYNOTE-054 trial 6

A complete staging evaluation before treatment decisions is recommended, including chest/abdomen/pelvic CT scan, brain MRI with contrast, and consideration of PET scan, as per the National Comprehensive Cancer Network and the European Society for Medical Oncology 2, 4
Serum LDH is an independent predictor of poor outcome and should be included in the staging workup, according to the American Joint Committee on Cancer 4

Stage III melanoma has 5-year survival rates ranging from 30-70% depending on nodal tumor burden, as reported by the National Comprehensive Cancer Network 2
With modern adjuvant immunotherapy, 3-year recurrence-free survival approaches 60%, according to the American Society of Clinical Oncology 1