A 72-year-old man with a history of multiple nonmelanoma skin cancers presents with a 3 cm ulcerated, poorly differentiated squamous cell carcinoma on his right forearm. Despite two surgical excisions, the lesion has recurred and imaging now reveals involvement of regional lymph nodes. What is the most appropriate systemic therapy for this patient?

A. Cetuximab

B. Cemiplimab

C. 5-Fluorouracil

D. Vismodegib

E. Radiation therapy alone

Rationale:

Squamous cell carcinoma is the second most common cutaneous malignancy. Aggressive squamous cell carcinoma occurs in approximately 5% of patients with squamous cell carcinoma. It is prudent that dermatologists and surgeons recognize when surgery alone is not sufficient or appropriate. In this example, the patient has failed surgical treatment twice and has developed lymph node involvement necessitating escalation of therapy beyond surgical removal. 

Correct answer: B. Cemiplimab 

Cemiplimab is a PD-1 inhibitor approved for the treatment of locally advanced or metastatic SCC, particularly in patients who are not candidates for curative surgery or radiation. It has demonstrated efficacy in inducing durable responses in patients with advanced SCC. As an immune checkpoint inhibitor, Cemiplimab enhances anti-tumor immune activity. 

Incorrect answers:

A. Cetuximab is an EGFR inhibitor that can be used off-label for SCC but is not the first-line therapy for metastatic or locally advanced SCC. It has limited durability of response compared to PD-1 inhibitors like Cemiplimab.

C. 5-FU is a topical or systemic chemotherapeutic agent primarily used for superficial SCC or actinic keratoses. It is not effective for metastatic or locally advanced disease.

D. Vismodegib inhibits Smoothened and is considered a hedgehog pathway inhibitor. It is approved for advanced basal cell carcinoma, not SCC. It does not have a role in the management of squamous cell carcinoma.

E. Radiation therapy is useful for local control in SCC but is not sufficient as monotherapy for regional lymph node involvement or metastatic disease. It can be combined with systemic therapy in certain situations. 

Additional reading at Skin Cancer a Comprehensive Guide Chapter 47: Immunomodulators of Skin Cancers

References:

1. Mager L, Gardeen S, Carr DR, Shahwan KT. Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives. Clin Cosmet Investig Dermatol. 2023 Aug 9;16:2135-2142. doi: 10.2147/CCID.S381471. PMID: 37581012.