INTRODUCTION
Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer, and its incidence is rising.1,2 The majority of cSCC are cured by surgical interventions (ie, wide local excision and Mohs micrographic surgery), though there is a substantial number of patients who develop locoregional or distant recurrence (4%) and who will die from the cancer (0.5%).3-5 High-risk features for metastasis include immunosuppression, perineural invasion (PNI), recurrence, poor differentiation, and extracapsular invasion on histology, and more recently, the 40-gene expression profile (40-GEP Class 2A and Class 2B).6-8 Those with a high risk of worse outcomes may benefit from more intensive management, including adjuvant radiation therapy (ART), which has demonstrated efficacy in reducing local recurrence (LR) and locoregional recurrence (LRR) following clear margin surgery.9,10
Commonly used staging systems from the American Joint Committee on Cancer (AJCC) 8th edition, Brigham and Women's Hospital (BWH), and the National Comprehensive Cancer Network (NCCN) all have distinctive ways of classifying cSCC as high-risk based on clinicopathologic features.11-14 However, these staging systems have limited accuracy, and no system is consistently used by physicians.15 These differences in approaches and limited predictive accuracy lead to a lack of uniformity in the management of high-risk cSCCs following surgical excision with clear margins.14,16,17 With this lack of agreement on which staging system or risk factors should be used to guide care, the literature has reported that predicting which patients with cSCC may benefit from ART is unclear.9,16 Current NCCN guidelines differentiate between low-risk, highrisk, and very high-risk factors to help identify the cSCC that carry a significant risk of poor outcomes. Both high-risk and very high-risk diseases have established management workflows that include consideration of ART among other interventions.
Despite the clear benefits of ART in certain patient populations, no predictive clinical or pathological factors have been identified to guide who is likely to benefit from ART. Further, the benefits of ART should be weighed against the risks related to ART, including erythema, acute erosive dermatitis, cellulitis, depigmentation, and telangiectasias.
Commonly used staging systems from the American Joint Committee on Cancer (AJCC) 8th edition, Brigham and Women's Hospital (BWH), and the National Comprehensive Cancer Network (NCCN) all have distinctive ways of classifying cSCC as high-risk based on clinicopathologic features.11-14 However, these staging systems have limited accuracy, and no system is consistently used by physicians.15 These differences in approaches and limited predictive accuracy lead to a lack of uniformity in the management of high-risk cSCCs following surgical excision with clear margins.14,16,17 With this lack of agreement on which staging system or risk factors should be used to guide care, the literature has reported that predicting which patients with cSCC may benefit from ART is unclear.9,16 Current NCCN guidelines differentiate between low-risk, highrisk, and very high-risk factors to help identify the cSCC that carry a significant risk of poor outcomes. Both high-risk and very high-risk diseases have established management workflows that include consideration of ART among other interventions.
Despite the clear benefits of ART in certain patient populations, no predictive clinical or pathological factors have been identified to guide who is likely to benefit from ART. Further, the benefits of ART should be weighed against the risks related to ART, including erythema, acute erosive dermatitis, cellulitis, depigmentation, and telangiectasias.
