Neoadjuvant Systemic Therapy for High-Risk Melanoma Patients

The landscape of treatment options and outcomes for patients with locally advanced and metastatic melanoma has changed dramatically in the past decade, with the introduction of molecularly targeted antitumor therapy and immunotherapy. Despite these recent advances for advanced stage melanoma, stage III melanoma patients have heterogeneous outcomes and have highly variable prognosis with respect to risk of loco-regional and distant recurrence and survival. Patients with clinical stage III disease, defined as those with palpable nodes with or without in-transit metastases, represent a high-risk population with poor outcomes even with the recent progress in adjuvant therapy. The full potential of targeted and immunotherapy, as well as other novel therapies, in the neoadjuvant setting is unknown and are only beginning to be investigated. Neoadjuvant therapy conveys advantages over administering the same treatment postoperatively as, in some cases, favorable response to treatment can make surgery less morbid and more effective. Additionally, response to therapy can be assessed and postoperative therapy adjusted accordingly depending on degree of response. Neoadjuvant therapy is associated with disadvantages as well; the exact stage of disease may be unknown when treatment begins, and adverse effects of treatment can negatively impact planned surgery or increase the risk of postoperative complications. The results of ongoing and future neoadjuvant clinical trials will undoubtedly shape the standard of care for patients with locally advanced melanoma at high risk of recurrence. Ultimately, enhanced selection of patients for systemic therapy prior to surgery could delay or prevent distant metastatic disease and improve survival for melanoma patients.