Adjuvant Nodal Radiation Therapy for Melanoma in the Era of Immunotherapy

In the last few years there have been dramatic changes in the management of patients with melanoma with locally advanced disease. Previously, standard therapy for melanoma patients with nodal disease involved completion lymph node dissection followed by adjuvant radiation therapy for high-risk features, as defined by TROG 02.01. Adjuvant systemic therapy with interferon could be offered, but many eligible patients did not receive this agent in the context of significant toxicity. New, effective, and often well-tolerated systemic therapies, such as immune checkpoint inhibitors and targeted MAPK pathway inhibitors, have shown impressive responses in metastatic disease and are now being applied to the locally advanced setting. Currently, for patients with occult nodal disease found at sentinel lymph node biopsy, completion lymph node dissection is uncommon with adjuvant anti-PD1 therapy often recommended. For patients with clinically apparent nodal disease, neoadjuvant immunotherapy has shown impressive pathologic response rates, which thus far have correlated well with longer term disease outcomes. However, not all patients exhibit a robust pathologic response. In circumstances of either occult nodal disease or clinically evident nodal disease without a robust pathologic response to neoadjuvant immunotherapy, there is a dearth of evidence regarding the optimal use of radiation therapy. Prospective studies investigating the role of adjuvant nodal radiation therapy for melanoma patients in the modern immunotherapy era are much needed.