ESMO E-Learning: Cutaneous Squamous Cell Carcinomas (CSCC)

This E-Learning module provides in depth information about the epidemiology of cutaneous squamous cell carcinomas (CSCC), the role of different treatment modalities (surgery, radiotherapy, systemic treatment) in the management of these patients and elaborate a future outlook in terms of research of such a small patient population, but with great medical needs.

The author states that surgery is generally curative for patients with high-stage CSCC, including those with early nodal disease, but it is not an option for a small subset of patients.

Previously, these patients were treated with chemotherapy and off-label EGFR inhibitors. Response rates averaged 20% between agents, with low durability and high recurrence risk.

PD-1 inhibitors have shown efficacy in patients with CSCC ineligible for surgery, mainly due to the high tumour mutational burden associated with CSCC. Currently, cemiplimab is the only approved agent for unresectable CSCC in Europe. Response rates are around 40% to 50%, with high durability and lasting control. Both cemiplimab and pembrolizumab are approved in the US.

Checkpoint inhibitors stimulate the immune system, which can be a problem for some patients, such as immunosuppressed patients. The author advises that eligibility for immunotherapy should be evaluated on a case-by-case basis with a need for multicentre studies in immunocompromised patients.

Immune-related adverse events (irAEs) can happen at any time and can affect any organ system. Corticosteroids are the cornerstone of management, along with treatment holidays and drug discontinuation in more severe cases. Non-thyroid endocrine irAEs are usually permanent and affect about 1% of patients.

Future research agenda in CSCC encompasses strategies with combination of PD1 inhibitors with irradiation, targeted agents, such as cetuximab, lenvatinib, intralesional agents like oncolytic viruses, with CTLA-4 antibodies, etc. The author also emphasizes about high medical need particularly for patients with PD1-refractory CSCC.