Managing Advanced Squamous Cell Carcinoma: A Guide for the Dermatology Clinician

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. Advanced cSCCs encompass locally advanced cSCC (laCSCC), including primary or recurrent tumors that are not amenable to curative surgery or radiation therapy, and metastatic (locoregional or distant) cSCCs (mCSCC). With the development of immunotherapies (eg, PD-1 inhibitors), there may be an enhanced opportunity to effectively treat advanced cSCC. We aim to review the current literature on therapeutic options and outline treatment strategies to optimize care for patients with advanced cSCC.

A comprehensive literature search was completed using the keywords "advanced cutaneous squamous cell carcinoma," "treatment," "surgery," "radiotherapy," "immunotherapy," "PD1-inhibitor," "cemiplimab," and "pembrolizumab". The authors reviewed all studies and included those which addressed the topic of the review.

Advanced cSCCs may not be amenable to surgery or radiotherapy due to size, location, and other aggressive features. Identifying advanced cSCCs and managing patients with multiple tumors and/or those with high tumor burden can be challenging and utilizing current evidence-based guidelines and staging systems can help selection of appropriate therapeutic options. Systemic immunotherapies such as cemiplimab and pembrolizumab have growing evidence for use as a first-line treatment for advanced cSCCs. It is important to understand the adverse event profile of these immunotherapies as utility may be limited by adverse events.

This is a review article and is limited by the information available in the published literature. In addition, comparison between studies is limited as varying methodologies were used.

Advanced cSCCs can be difficult to manage and involving a multidisciplinary team is essential. For laCSCCs and mCSCCs not amenable to surgery or radiotherapy, cemiplimab and pembrolizumab can be effective therapeutic options.