Guideline Updates Refine Risk Stratification and Diagnosis in CSCC

Recent updates to the National Comprehensive Cancer Network (NCCN) guidelines for cutaneous squamous cell carcinoma (CSCC) introduce more refined risk stratification and emphasize improved diagnostic techniques, both of which can significantly influence treatment planning, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center.

Historically, CSCC tumors were categorized simply as low risk or high risk. However, Patel explains that this framework did not fully capture the varying degrees and types of risk patients face, such as recurrence, metastasis, or disease-specific mortality. The updated guidelines now divide high-risk tumors into high-risk and very-high-risk categories, enabling clinicians to better tailor treatment strategies.

Very-high-risk disease includes tumors with features associated with particularly poor outcomes, such as in-transit metastases, tumors larger than 4 cm, poor differentiation, and lymphovascular invasion. Identifying these features at diagnosis can prompt clinicians to consider treatments beyond surgery alone. In these cases, patients may benefit from neoadjuvant systemic therapy prior to surgery or adjuvant therapy after surgery, particularly when evidence suggests a substantial risk of recurrence or disease progression. Patel notes that specific criteria from clinical trials evaluating adjuvant therapy—such as those informing the approval of cemiplimab in high-risk settings—should also be considered when determining eligibility for additional treatment.

The guidelines also place greater emphasis on performing deeper biopsies when evaluating suspicious lesions. Patel explains that CSCC tumors are often heterogeneous, meaning the superficial portion of a lesion may not reflect its true aggressiveness. Superficial biopsies can therefore miss critical features such as depth of invasion, perineural invasion, or extension into subcutaneous fat—factors that can significantly increase tumor stage and risk classification.

Obtaining biopsy samples that extend into the dermis or deeper allows pathologists to accurately assess tumor thickness and other high-risk features, similar to staging considerations in melanoma. Without adequate sampling, clinicians may underestimate disease severity, leading to under-staging and potentially suboptimal treatment planning.

Together, improved risk stratification and more thorough biopsy practices help clinicians better identify patients who may require more aggressive, multidisciplinary care.