European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment - update 2026
- Study type
- Clinical guideline
- Study name
- EADO/EDF/ESTRO/UEMS-DV/EORTC cSCC 2026
- Design
- European interdisciplinary guideline based on evidence and expert consensus (EADO, EDF, ESTRO, UEMS-DV and EORTC); update of the 2023 version
- Source
- Eur J Cancer · 2026
In plain words
This European guideline says that the main treatment for squamous cell skin cancer is complete removal with surgery, making sure the edges are clear; if surgery is not possible, radiotherapy is the alternative. In advanced disease that cannot be cured with surgery or radiotherapy, immunotherapy is the first treatment. After surgery and radiotherapy in high-risk patients, a multidisciplinary team decides about immunotherapy. Patients should share in decisions, and the follow-up plan depends on the level of risk.
Key guideline recommendations
For common primary CSCC, first-line treatment is surgical excision with post-operative margin assessment or micrographically controlled surgery; achieving clear histological margins is key.
Radiotherapy should be considered for patients or tumours that are not candidates for surgery.
For macroscopic regional lymph node metastases, individualised treatment should be discussed in a multidisciplinary tumour board.
In metastatic or locally advanced CSCC not suitable for curative surgery or radiotherapy, anti-PD-1 agents are the first-line systemic treatment (cemiplimab is the EMA-approved agent).
Second-line treatment: clinical trials, an EGFR inhibitor (cetuximab) combined with anti-PD-1 immunotherapy, or chemotherapy or radiotherapy.
The decision on adjuvant cemiplimab for CSCC at high risk of recurrence after surgery and radiotherapy should be discussed in a multidisciplinary tumour board.
Multidisciplinary board decisions are mandatory for all patients with advanced CSCC, weighing the risk of toxicity, age, frailty and comorbidities, including immunosuppression.
Patients should take part in informed, shared decision-making and receive the best supportive care for symptom control and quality of life.
The frequency of follow-up visits and investigations for new CSCC should be set according to the underlying risk characteristics.
Study population
This document is a guideline and did not enrol patients. Target population: immunocompetent and immunosuppressed patients with invasive cutaneous squamous cell carcinoma (cSCC), from common primary tumours to locally advanced disease, regional metastases and distant metastases.
Endpoints
Recommendations on treatment, supportive care and follow-up; no clinical endpoint defined.
Safety and side effects
For all patients with advanced disease, decisions should be made in a multidisciplinary tumour board, taking into account the risk of toxicity, age, frailty and comorbidities, including immunosuppression.
Clinical significance and place in guidelines
The latest European cSCC guideline, which brings adjuvant cemiplimab after C-POST into tumour board decisions for high-risk patients after surgery and radiotherapy and considers anti-PD-1 therapy first line for advanced disease. Part 1 of the same update (diagnostics and prevention) introduces the “easy-to-treat” and “difficult-to-treat” categories and five difficult-to-treat groups, considers histological confirmation always necessary and AJCC8 and BWH the most widely used staging systems, and lists oral nicotinamide and sun protection among the ways of prevention.
Limitations
The abstract does not report levels of evidence, grades of recommendation or details of surgical margins and doses, and the recommendations on this card are taken from the abstract of Part 2; check the full text. Some recommendations rest on expert consensus.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.