Merkel Cell Carcinoma: Evolving Therapeutics, Continued Challenges.

Background: Merkel Cell Carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy with rising incidence, influenced by ultraviolet (UV) radiation and Merkel cell polyomavirus (MCPyV).

Methods: 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.

Results: 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.

Conclusion: 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.