Merkel Cell Carcinoma: Evolving Therapeutics, Continued Challenges.

Abstract

Merkel Cell Carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy with rising incidence, influenced by ultraviolet (UV) radiation and Merkel cell polyomavirus (MCPyV). This review summarizes recent advances in MCC management, based on an analysis of current literature, focusing on immune checkpoint inhibitors (ICIs), viral status implications, and evolving multimodal treatment strategies. MCPyV-positive MCC has a median overall survival (OS) of 6.6 years compared to 1.2 years for virus-negative cases. The 5-year OS rate for localized MCC is approximately 50%. Historically, the 5-year OS for metastatic MCC was ~14%, but has significantly improved with ICIs. First-line treatment with avelumab achieved a median OS of 20.3 months and a 5-year OS of approximately 26%. Pembrolizumab demonstrated a median OS of 24.3 months, a median progression-free survival (PFS) of 9.3 months, and a durable response with a median duration of response (DOR) of 39.8 months. Despite advances, MCC recurrence rates remain high (16.4% local, 32.1% regional, 9.5% distant), necessitating vigilant long-term surveillance. Future research should focus on optimizing combination therapies, identifying predictive biomarkers, and refining treatment sequencing to further improve survival and quality of life.