Loading
10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Advanced cutaneous squamous cell carcinoma is a skin cancer that has grown beyond what surgery or radiotherapy can remove or has spread to lymph nodes or organs. Because sun damage gives it more mutations than almost any other cancer, immunotherapy works well: cemiplimab or pembrolizumab shrinks about half of tumours, often for years, and cemiplimab before surgery can make large tumours vanish.
Cutaneous squamous cell carcinoma arises from keratinocytes of sun-damaged skin and carries one of the highest mutation burdens of any human cancer, with TP53, NOTCH1 and CDKN2A mutations in most tumours. High-risk features are size over 2 centimetres, depth beyond fat, perineural or lymphovascular invasion, poor differentiation, ear or lip site and immunosuppression; these tumours recur, spread to parotid and cervical nodes and account for most deaths. Advanced disease is defined as locally advanced disease not curable by surgery or radiotherapy, or nodal or distant metastasis. Before 2018 the only systemic options were cetuximab, with responses in about a quarter of patients, and platinum-based chemotherapy with short-lived responses.
EMPOWER-CSCC-1 (2018) showed the PD-1 antibody cemiplimab produced responses in 47 percent of patients with metastatic disease and 46 percent in the pooled analysis of 193 patients, most of them durable, and it became the first approved drug for the disease in September 2018. KEYNOTE-629 (2020) found pembrolizumab produced responses in 34 percent of recurrent or metastatic and 50 percent of locally advanced tumours, and cosibelimab, a PD-L1 antibody, was approved in December 2024. Responses are less frequent in transplant recipients, in whom PD-1 blockade also risks graft rejection, and switching immunosuppression to a mammalian target of rapamycin inhibitor is one strategy.
| Setting | Approach | Guideline |
|---|---|---|
| High-risk resectable disease | Excision with margin control or Mohs surgery, nodal evaluation, and postoperative radiotherapy for perineural invasion, positive margins or nodal disease; neoadjuvant cemiplimab to shrink large tumours before surgery. | not mapped |
| Adjuvant after surgery and radiotherapy | Cemiplimab for high-risk disease (C-POST, 2025). | not mapped |
| Locally advanced or metastatic, first line | Cemiplimab (EMPOWER-CSCC-1), pembrolizumab (KEYNOTE-629) or cosibelimab; radiotherapy for symptomatic sites. | not mapped |
| Immunotherapy-ineligible or refractory | Cetuximab with or without radiotherapy, platinum-based chemotherapy, capecitabine; clinical trials of RP1 with cemiplimab or photoimmunotherapy. | not mapped |
| Transplant recipients | Reduce immunosuppression and switch to sirolimus or everolimus where possible; PD-1 blockade only after weighing graft rejection risk; surgery and radiotherapy preferred. | not mapped |