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

## TL;DR

This review discusses how immunotherapy is improving treatment for skin cancer in older adults, especially in aging societies like East Asia.

## Contribution

The paper integrates geriatric oncology and immunosenescence perspectives to guide immunotherapy use in aging populations.

## Key findings

- Immune checkpoint inhibitors like cemiplimab and pembrolizumab show comparable efficacy and safety in East Asian patients.
- Frailty assessment and individualized treatment goals are crucial for optimizing care in older patients with advanced cSCC.
- Real-world data from East Asia support the global relevance of immunotherapy for diverse patient groups.

## Abstract

Cutaneous squamous cell carcinoma is one of the most common skin cancers, especially in older adults. With the rapid aging of societies, particularly in East Asia, the number of very old patients with this disease is increasing. Although surgery and radiotherapy can cure early-stage tumors, advanced or unresectable cases have been difficult to manage. In recent years, new medicines called immune checkpoint inhibitors have offered major improvements, helping many patients live longer with fewer side effects than those of older treatments. This review explains how these drugs are being used in patients with advanced disease, especially in older groups who may have other health problems or reduced physical strength. We also highlight the importance of careful evaluation of frailty, daily function, and other age-related issues when deciding on treatment. We aim to guide doctors and researchers in adapting skin cancer care to the realities of aging societies.

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.