SPECIAL COMMENTARYAdvanced cutaneous squamous cell carcinoma: how is it defined and what new therapeutic approaches are available?Soura, Efthymiaa; Gagari, Elenib; Stratigos, AlexanderaAuthor Information aMelanoma and Skin Cancer Center bOral Disease Unit, 1st Department of Dermatology-Venereology, National and Kapodistrian University of Athens Medical School, ‘Andreas Sygros’ Hospital, Athens, Greece Correspondence to Alexander Stratigos, MD, 1st Department of Dermatology – Venereology, Andreas Sygros Hospital, 5 I. Dragoumi Str, 16 121, Athens, Greece. Tel: +302107265100; fax: +302107258476; e-mail: [email protected] Current Opinion in Oncology: September 2019 - Volume 31 - Issue 5 - p 461-468 doi: 10.1097/CCO.0000000000000566 Buy Metrics Abstract Purpose of review Despite the overall excellent survival rates in patients with cutaneous squamous cell carcinoma (cSCC), advanced cutaneous SCCs are associated with high patient morbidity and mortality. Therefore, important unmet clinical needs persist: identifying high risk patients and choosing optimal treatment approaches. Recent findings In recent years, a better understanding of the biology of cSCC and its clinical progression have led to improved staging systems and new promising treatments for advanced disease. Such treatments include PD1 inhibitors, such as cemiplimab, which was recently approved for the treatment of cutaneous SCC, and pembrolizumab whose efficacy in the treatment cSCC is still being investigated. Other treatments, such as epidermal growth factor receptor inhibitors have also been used in the treatment of cSCC with moderate success. Several clinical and histological risk factors are considered key in estimating the risk or recurrence or metastasis in cSCCs and, therefore, influence the appropriate treatment choice and patient monitoring. Summary The present study reviews the current definition of advanced cSCC and discusses the new systemic approaches, including checkpoint inhibitors. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.