Practice guidelines are crucial in improving the care and outcomes for patients with cSCC. The most recent National Comprehensive Cancer Network (NCCN) guidelines, updated in 2024, offer clinicians guidance on diagnostic considerations, risk assessment, and treatments. These guidelines also cover new information on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy. They are based on evidence and help determine the best treatment approaches for patients with different levels of severity.1
Due to the generally low probability of metastasis and death in patients with cSCC, accurate risk stratification is crucial. Proper risk stratification allows for the appropriate interventions for high-risk patients while avoiding overtreatment in low-risk patients, ultimately improving patient outcomes.1
Current methods for risk assessment in cSCC vary widely and rely on high-risk tumor characteristics and patient demographics, such as immune status, as defined by current staging systems. Despite these efforts, the positive predictive values for adverse outcomes remain low. Key risk factors for local recurrence, nodal or distant metastasis, and disease-specific death include perineural invasion, histological differentiation status, depth of invasion, and tumor size and location.2
The NCCN guidelines recommend tailoring the extent and intensity of intervention based on the presence and number of these risk factors. However, traditional risk assessment methods, which focus solely on clinical and histopathologic features, are limited in accurately identifying patients at high risk for metastatic disease.1
