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October 2022BACKGROUND
Stage III melanoma encompasses a heterogenous group of patients with significant differences in locoregional recurrence risk, prognosis, and survival. Stage IIIA melanoma patients present with minimal metastatic burden identified by sentinel lymph node biopsy and have favorable outcomes compared to stage IIIB patients with clinical regional disease. Locoregional failure rates ranging from 30% to 50% have been reported when high-risk clinicopathologic features are present. Prior to the approval of systemic therapy in stage III melanoma, studies recommended adjuvant radiation therapy (RT) for patients with extra-nodal extension, lymph nodes larger than 3 cm, involvement of multiple lymph nodes, recurrent disease, or any patient having undergone a therapeutic neck dissection (Cancer. 2003;97:1789–1796). Adjuvant RT for high-risk cutaneous melanoma was shown to improve loco-regional recurrence; however, it failed to improve recurrence-free survival and overall survival.
The majority of the studies that investigated the benefit of RT on local and regional control in stage III melanoma were conducted prior to the era of an effective adjuvant systemic immune checkpoint inhibitor and targeted therapy. The role of adjuvant radiotherapy in the era of modern systemic therapies is unclear.
BEST PRACTICE
In the era of effective adjuvant systemic therapies, the use of an immune checkpoint inhibitor alone in the adjuvant setting may be insufficient to effectively reduce regional failure. Adjuvant RT may still have a significant value in improving regional control in stage III melanoma. Future studies should focus on whether select patient populations benefit from combination therapy. This recommendation is based on level 3 evidence (nonrandomized controlled cohort/follow-up study, cohort study or control arm of the randomized trial).