Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma

OBJECTIVE: Over 50% of newly diagnosed cutaneous squamous cell carcinoma (cSCC) lesions occur in the head and neck (cSCC‐HN), and metastasis to nodal basins in this region further complicates surgical and adjuvant treatment. The current study addressed whether the 40‐gene expression profile (40‐GEP) test can predict metastatic risk in cSCC‐HN with improved accuracy and provide independent prognostic value to complement current risk assessment methods. STUDY DESIGN: Multicenter, retrospective cohort study. METHODS: Formalin‐fixed paraffin‐embedded primary tumor tissue and associated clinical data from patients with cSCC‐HN (n = 278) were collected from 33 independent centers. Samples were analyzed via the 40‐GEP test. Cases were staged per American Joint Committee on Cancer, Eighth Edition (AJCC8) and Brigham and Women's Hospital (BWH) criteria after comprehensive medical record and pathology report review. Metastasis‐free survival (MFS) rates were determined, and risk factors were analyzed via Cox regression. RESULTS: The 40‐GEP test classified the cohort into low (Class 1, n = 126; 45.3%), moderate (Class 2A, n = 134; 48.2%), and high (Class 2B, n = 18; 6.5%) metastatic risk at 3 years postdiagnosis. Regional/distant metastasis occurred in 54 patients (19.4%). MFS rates were 92.1% (Class 1), 76.1% (Class 2A), and 44.4% (Class 2B; p < .0001). Multivariate analysis of 40‐GEP results with AJCC8 or BWH tumor stage, or clinicopathologic risk factors, demonstrated independent prognostic value of the 40‐GEP test (p < .03). Accuracy of predicting metastatic risk was also improved using 40‐GEP classification (p < .02). CONCLUSIONS: Improved metastatic risk stratification through the 40‐GEP test could complement cSCC‐HN risk assessment for better‐informed decision‐making for treatment and surveillance and ultimately improve patient outcomes. LEVEL OF EVIDENCE: 3