Rethinking locoregional therapy of Merkel cell carcinoma in the era of immune checkpoint inhibition

Abstract

Merkel cell carcinoma (MCC) is a highly aggressive yet profoundly immunotherapy-sensitive skin cancer characterized by early nodal and systemic dissemination. Historically, aggressive locoregional treatment was considered essential because therapeutic options for advanced disease were limited. The advent of immune checkpoint inhibitors has fundamentally transformed outcomes in MCC and, for the first time, enabled critical reassessment of established surgical and radiotherapeutic paradigms. Contemporary evidence suggests that intensified locoregional therapy does not consistently improve survival, which appears to be driven primarily by occult systemic disease. Emerging perioperative immunotherapy data therefore support more individualized, biology-driven strategies, including potential de-escalation of local therapy in selected patients while maintaining effective oncologic control.