Abstract The global incidence of cutaneous squamous cell carcinoma (CSCC) has increased significantly over the past 30 years. In the UK, between 2000 and 2010, there was a 34% rise in cases among males and a 39% rise among females. Non-melanoma skin cancers (NMSC) account for approximately 20% of all newly diagnosed malignancies and 90% of skin cancers worldwide (1). Advanced CSCC includes both locally advanced (laCSCC) and metastatic (mCSCC) disease, the latter involving regional or distant spread. Mortality rates in patients with advanced CSCC, particularly those with metastases, can exceed 70% in some cohorts (2). In recent years, immunotherapy has emerged as a promising treatment option, especially for patients with unresectable or treatment-resistant disease. Immune checkpoint inhibitors, particularly PD-1 inhibitors, have demonstrated significant clinical benefit, with trials reporting complete remission in over 60% of patients with advanced CSCC(3). Accordingly, the British Association of Dermatologists recommends their use in cases of locally advanced or metastatic disease. We present three cases of advanced CSCC with clinical and radiological regression following immunotherapy, illustrating its increasing role in treatment. Additionally, we review current literature on the efficacy and safety of immunotherapy, associated adverse effects, and the clinical challenges in managing advanced CSCC. As there remains no universally defined treatment pathway for patients with unresectable or metastatic disease, and with some patients becoming non-responsive to surgery or radiotherapy, systemic therapies such as immunotherapy represent a critical and evolving treatment strategy.
Kaur et al. (Sun,) studied this question.