Merkel Cell Carcinoma: Current Treatment Landscape and Emerging Therapeutic Targets

Abstract

Purpose of review: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine carcinoma that is primarily driven by Merkel cell polyomavirus (MCPyV) and ultraviolet radiation. Due to its rarity and innocuous appearance on clinical exam, MCC diagnosis is often delayed and therefore diagnosed at advanced stages. Overall survival outcomes are poor and notably worse than melanoma, with an estimated five-year survival ranging from 35 to 60% for stage I or II disease to < 15% for metastatic disease. Our review examines the diagnostic workup, prognostic markers, and current and emerging treatments of MCC.

Recent findings: For local disease in which surgical resection is feasible, tumor removal with potential adjuvant radiation therapy is the primary treatment modality. Immunotherapy with PD-1 / PD-L1 inhibitors is now standard for advanced disease where complete resection is not feasible. Additionally, there are many ongoing clinical trials examining novel immune checkpoint inhibitors, immunomodulators, targeted therapies, cellular therapies, vaccines, and oncolytic virus therapies with the goal of improving outcomes for patients with advanced disease or those who experience recurrence after first-line immunotherapy. MCC is an aggressive disease with a rapidly evolving treatment landscape, and emerging therapies hold the potential to improve prognosis in advanced disease.

Keywords: Checkpoint inhibitor; Immunotherapy; Merkel cell carcinoma; Merkel cell polyomavirus (MCPyV); PD-1; PD-L1.