The 40-Gene Expression Profile Test Identifies Patients with National Comprehensive Cancer Network High-Risk Cutaneous Squamous Cell Carcinoma at High Risk of Poor Outcomes to Inform Management Decisions

Main Article Content

Désirée Ratner
Sarah T. Arron
Yeon Joo Kim
Lenka V. Hurton
Elise Ng
Brian J. Martin
Jason M. Rizzo

Keywords

40-gene expression profile (40-GEP), GEP, high-risk, local recurrence, metastatic cSCC, prognostic testing, recurrence free survival, Cutaneous Squamous Cell Carcinoma

Abstract

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. 

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