Management Approaches for High-Risk Cutaneous Squamous Cell Carcinoma with Perineural Invasion: An Updated Review.

Opinion statement: Cutaneous squamous cell carcinoma (cSCC) stands as the second most prevalent non-melanoma skin cancer worldwide, comprising approximately 20% of all cutaneous malignancies. Determining its precise incidence poses challenges; however, reports indicate a global increase in its prevalence. At the time of diagnosis, the majority of cSCCs are localized, resulting in favorable 5-year cure rates surpassing 90%. Nevertheless, a subset of patients (3-7%) encounters locally advanced or metastatic cSCC, leading to substantial morbidity and mortality. The risk of metastasis ranges from 0.1% to 9.9%, carrying an associated mortality risk of 2.8%. Factors influencing recurrence, metastasis, and disease-specific mortality underscore the significance of perineural invasion (PNI) as a key indicator. Patients with PNI may manifest clinical symptoms and/or radiologic signs of PNI, while the majority remain asymptomatic, and PNI is frequently identified upon histologic examination. Despite its lower frequency compared to other cancer types, PNI serves as a recognized adverse prognostic factor for cSCC. Surgery is the elective treatment for these patients, while the role of adjuvant radiotherapy (ART) is yet contentious and have not been conclusively assessed, particularly in clear surgical margin. Prospective comparative studies are required to comprehensively evaluate the benefit and the risks of ART for cSCC and PNI patients.