Immunotherapy for Cutaneous Squamous Cell Carcinoma in Aging Societies: Integrating Immunosenescence and Geriatric Oncology Perspectives

老龄化社会中皮肤鳞状细胞癌的免疫疗法:整合免疫衰老和老年肿瘤学视角

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Abstract

BACKGROUND/OBJECTIVES: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer worldwide, with a steadily increasing incidence in aging populations, particularly among older and immunocompromised individuals. Early-stage cSCC disease is usually managed with surgery or radiotherapy; however, advanced or unresectable cases remain therapeutically challenging. The advent of immune checkpoint inhibitors (ICIs), especially programmed cell death protein 1 inhibitors, such as cemiplimab and pembrolizumab, has markedly improved outcomes in advanced cSCC. Nevertheless, resistance to immunotherapy, management of frail or super-aged patients, and optimal integration of systemic therapy with radiotherapy continue to pose important clinical questions. METHODS: This review provides an updated overview of the current treatment strategies for cSCC, with particular attention to recent advances in systemic therapy and the application of geriatric oncology principles. We emphasize the considerations relevant to East Asian practices, especially in Japan, where the demographic shift toward a super-aged society magnifies the need for tailored approaches. RESULTS: Although most pivotal clinical trials have been conducted in Western populations, emerging real-world data from East Asia have demonstrated comparable efficacy and safety of ICIs, underscoring the global relevance of immunotherapy in diverse patient groups. By incorporating a structured frailty assessment, individualized treatment goals, and proactive management of immune-related adverse events, this review highlights practical strategies for optimizing cSCC care in older patients. CONCLUSIONS: Future directions include predictive biomarker development; refinement of treatment sequencing; and multidisciplinary collaboration among oncology, dermatology, and geriatrics to adapt cSCC management to aging societies.

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