Update of advanced cutaneous squamous cell carcinoma

Area of Science:

• Oncology
• Dermatology
• Immunology

Background:

• Cutaneous squamous cell carcinoma (cSCC) incidence is increasing, with a notable rise in immunocompromised individuals like organ-transplant recipients (OTR).
• While most cSCC cases are benign, a subset can progress to locally advanced or metastatic disease, posing significant clinical challenges.
• Accurate risk stratification is crucial for effective management, necessitating improved understanding of cSCC behavior.

Purpose of the Study:

• To highlight the increasing incidence of cSCC, particularly in immunocompromised populations.
• To emphasize the need for better discrimination between low- and high-risk cSCC for improved patient outcomes.
• To discuss current and emerging therapeutic strategies for advanced and metastatic cSCC.

Main Methods:

• Review of current literature on cSCC incidence, risk factors, and clinical behavior.
• Analysis of advancements in cSCC staging systems.
• Exploration of the potential role of genetic characterization in risk stratification.
• Overview of existing and novel treatment modalities for advanced cSCC.

Main Results:

• cSCC is increasingly diagnosed, with a significant proportion occurring in immunocompromised patients (e.g., OTR).
• Existing staging systems are being refined to better classify cSCC risk.
• Genetic characterization shows promise for distinguishing high-risk cSCC with metastatic potential.
• Anti-PD-1 antibodies demonstrate high response rates (up to 50%) in advanced/metastatic cSCC, though not currently suitable for OTR.

Conclusions:

• Understanding cSCC clinical behavior is vital for differentiating low- and high-risk cases.
• Genetic profiling is expected to play a key role in future risk stratification of cSCC.
• While advanced treatments like anti-PD-1 antibodies are effective, patient-specific considerations (e.g., immunosuppression) are critical for treatment selection.