Clinical stage III
melanoma, defined as resectable RECIST measurable nodal disease with or without in-transit
metastases, represents approximately 15% of new
melanoma diagnoses every year with additional cases presenting as recurrent nodal disease following previous treatment of a primary
melanoma. The standard of care for patients with resectable clinical stage III
melanoma is surgical resection, consisting of therapeutic
lymph node dissection and/or resection of in-transit disease and consideration of adjuvant systemic
therapy and occasionally adjuvant radiation. These patients have high rates of regional recurrence and progression to metastatic disease postsurgery, highlighting the need for better treatment options. With the success of
immune checkpoint inhibitors in both the adjuvant and metastatic settings, the use of these agents in the neoadjuvant setting has been an emerging area of research interest. In this chapter, we will discuss the rationale for neoadjuvant
immunotherapy; review impactful clinical trials; and define response monitoring, surgical considerations, emerging
therapies, and unanswered questions for
neoadjuvant therapy as a recent paradigm shift in the management of clinical stage III
melanoma.