Non-Excisional Treatment of Multiple Cutaneous Squamous Cell Carcinomas: A Narrative Review of Emerging Modalities and Clinical Outcomes

Cutaneous squamous cell carcinoma (cSCC) is a common and potentially aggressive non-melanoma skin cancer. While surgery is the standard of care, it is often unsuitable for patients with multiple lesions, high surgical risk, or tumors in anatomically sensitive locations. This narrative review synthesizes data from 12 clinical reports, case series, and trials evaluating non-excisional therapies for cSCC, including immunotherapy, photodynamic therapy (PDT), and epidermal growth factor receptor (EGFR) inhibitors. Cemiplimab, a PD-1 checkpoint inhibitor, was the most frequently used systemic agent and demonstrated disease control in both elderly and immunocompromised patients, with clearance rates as high as 100% and recurrence rates of 0% in several cases. PDT showed promise in pediatric patients and those with genetic conditions such as xeroderma pigmentosum and epidermodysplasia verruciformis. EGFR inhibitors like gefitinib and cetuximab were studied in patients with unresectable or metastatic cSCC, showing modest efficacy and greater toxicity. Across all modalities, adverse effects were generally mild and manageable, with fatigue and skin reactions being most common. Despite these promising results, studies were limited by small sample sizes, lack of comparators, and variable follow-up durations. This review highlights that non-surgical strategies can offer viable, function-preserving, and cosmetically favorable options for select cSCC patients and supports further exploration through controlled prospective trials.