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Introduction: Validate use of the 40-gene expression profile (GEP) to identify patients with National Comprehensive Cancer Network (NCCN) high-risk (HR) cutaneous squamous cell carcinoma (cSCC) who are at increased risk for local recurrence (LR) and metastasis, despite negative margins after surgical resection. Methods: NCCN HR cSCC patients with definitive negative margin Mohs surgery (n=414) from a previously published cohort were analyzed for risk prediction of local recurrence-free survival (LRFS) and metastasis-free survival (MFS) using Kaplan-Meier analysis with log-rank test. Multivariable Cox regression models were used to assess the effects of 40-GEP and NCCN HR clinicopathologic risk factors on LRFS. Results: The 40-GEP stratified NCCN HR patients, with low risk Class 1 patients having a higher 3-year LRFS and MFS than Class 2A or Class 2B patients (LRFS: 95.3% vs. 85.5% vs. 71.4%, P=0.001; MFS: 97.1% vs. 89.3% vs. 57.1%, P<0.001). BWH and AJCC staging systems were unable to stratify LRFS and MFS. Class 2A, Class 2B, PNI, and immunosuppression were identified as significant predictors of LR risk. Conclusions: In NCCN HR patients, 40-GEP testing stratifies LRFS and MFS and is therefore a significant predictor for both LR and metastasis above actionable pathway thresholds, enabling improved treatment decision-making for a patient subgroup who were previously challenging to reliably identify.
Ratner et al. (Wed,) studied this question.
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