A Comprehensive Narrative Review of the Challenges Surrounding Cutaneous SCC

Area of Science:

• Dermatology
• Oncology

Background:

• Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer (NMSC), predominantly affecting the head and neck.
• Increasing NMSC diagnoses present diagnostic and therapeutic challenges, particularly for high-risk cSCC.
• Metastasis occurs in approximately 5% of cSCC cases, with head and neck cSCC having a poor prognosis post-metastasis.

Purpose of the Study:

• To review risk factors for cSCC development.
• To outline criteria for defining high-risk cSCC.
• To examine treatment approaches for cSCC based on risk stratification.

Main Methods:

• Review of current literature on cSCC risk factors, classification, and treatment.
• Analysis of established staging systems (AJCC8, BWH) and their limitations.
• Exploration of emerging tools like gene expression profiling (GEP).

Main Results:

• High-risk cSCC is often larger, deeper, and involves perineural or vascular structures.
• Current staging systems have limitations in accounting for patient-specific factors.
• Adjuvant radiation therapy (ART) and systemic therapies (immune checkpoint inhibitors, EGFR inhibitors) are used for high-risk cSCC.

Conclusions:

• A standardized definition and approach for high-risk cSCC are needed.
• Individualized treatment decisions incorporating patient factors beyond conventional staging are crucial.
• Molecular tools like GEP show promise for improving prognostic accuracy and guiding treatment for high-risk cSCC, but require further validation.