European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention – Update 2026

Invasive cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers in white populations, accounting for 20% of all cutaneous malignancies. A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS)-Dermatology Venereology, and the European Organization of Research and Treatment of Cancer (EORTC), was formed to update guideline recommendations on CSCC (previous version 2023), based on current literature and expert consensus. Part 1 of the guidelines addresses diagnostics and prevention in immunocompetent as well as immunosuppressed patients. CSCC may be classified as easy-to-treat (vast majority) or difficult-to-treat, common primary CSCC, and is further defined as low risk or higher risk depending on the risk of recurrence or metastasis. A new classification of five groups of difficult-to-treat CSCC (DTT-CSCC) is proposed, published in 2025 by EADO experts and reflecting the commonly encountered clinical challenges. Difficult-to-treat (DTT) CSCC includes DTT-common CSCC groups 1 and 2 (which correspond to a subgroup of common CSCC that are complex to treat due to tumor and/or patient characteristics or multiplicity), DTT-CSCC group 3 corresponding to locally advanced CSCC, and DTT-CSCC groups 4 and 5 corresponding to CSCC with locoregional or distant metastases, respectively. The first step of diagnostics is based on clinical and dermatoscopic features, and is always confirmed by histopathology. The presence of risk factors characterizes higher risk CSCC, and the more risk factors, the higher the risk. After the histological diagnosis of CSCC has been established, the second step includes staging procedures, such as physical examination and, when indicated, imaging. In the third and final step, the clinical, histologic and radiologic findings are incorporated into staging systems. The more widely used staging systems are the American Joint Committee on Cancer 8th edition (AJCC8) and the Brigham and Women’s Hospital (BWH) systems. Prevention strategies include oral nicotinamide and sun protection measures.