Evaluating the Clinical Efficacy, Utility, and Role of the 40-Gene Expression Profiling Test in Assessing Prognosis of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel
November 2026 | Volume 25 | Issue 11 | 1051 | Copyright © November 2026
Published online October 30, 2026
Joshua Burshtein MDa, Angela Rosenberg DOb, Sarah T. Arron MD PhDc, Brooke Bartley MDb, David Cotter MD PhDd, Seemal R. Desai MDe,f, Lauren DeBusk MDb, Aaron Farberg MDg, Harrison P. Nguyen MD MBA MPHh,i,j, Todd Schlesinger MDk, l, Milaan Shah MDm, Danny Zakria MD MBAn, Nathalie Zeitouni MDo,p, Darrell Rigel MD MSbq
aDepartment of Dermatology, University of Illinois Chicago, Chicago, IL
bDepartment of Dermatology, UT Southwestern Medical Center, Dallas, TX
cPremier Aesthetic Dermatology, San Carlos, CA; dLas Vegas Dermatology, Las Vegas, NV; eUniversity of Texas Southwestern
Medical Center, Dallas, TX; fInnovative Dermatology, Plano, TX; gBare Dermatology, University of North Texas Health Science Center,
Baylor Scott & White Health, Dallas, TX; hHarrison Dermatology & Research Group, Houston, TX; iTilman J Fertitta Family
College of Medicine, University of Houston, Houston, TX; jDepartment of Dermatology, Baylor College of Medicine, Houston, TX;
kClinical Research Center of the Carolinas, Charleston, SC; lDepartment of Dermatology, the George Washington University School
of Medicine and Health Sciences; mDepartment of Dermatology, Medical University of South Carolina, Charleston, SC;
nDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; oMedical Dermatology Specialists, Phoenix, AZ;
pUniversity of Arizona College of Medicine, Phoenix, AZ; qDepartment of Dermatology, NYU Grossman School of Medicine, New York, NY
Abstract
Background: The 40-gene expression profiling (40-GEP) test has been validated to identify patients at highest risk for nodal or distant metastasis, as well as those most likely to benefit from adjuvant radiation therapy (ART). The purpose of this expert consensus panel was to review the published literature on the clinical efficacy, utility, and role of the 40-GEP test in providing prognostic information for high-risk cSCC.
Methods: A comprehensive literature search was completed using a combination of keywords "40-gene expression profiling," "cutaneous squamous cell carcinoma," "prognosis," "clinical efficacy," and "clinical utility". A panel of 8 dermatologists with significant expertise in management of cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement, and a strength of recommendation was assigned.
Results: The literature search produced 55 articles. Screening resulted in 18 articles that met criteria. The panel unanimously "voted to adopt 8 consensus statements and recommendations: 5 with strength "A", 2 with strength "B", and 1 with strength "C.
Conclusion: The 40-GEP test augments staging accuracy by improving metastatic and local recurrence risk stratification beyond traditional staging systems. It also has clinical utility in informing decisions regarding adjuvant radiation therapy and guiding broader management strategies.
INTRODUCTION
Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer, and its incidence and prevalence are rising.1,2 Traditional treatment methods include surgical interventions (ie, wide local excision and Mohs micrographic surgery), though for select patients other interventions may be more appropriate or required (ie, radiation therapy, immunotherapy).3 cSCC has the potential to develop into metastatic disease, with approximately 4% of patients experiencing locoregional or distant recurrence and may lead to death.4-6 Therefore, patients with higher risk of poor outcomes from cSCC may benefit from more intensive management.
Identifying those at risk of recurrence and metastasis has been based on several staging systems available for cSCC, which include the American Joint Committee on Cancer 8th edition (AJCC8) and the Brigham and Women’s Hospital (BWH) staging system. The National Comprehensive Cancer Network (NCCN) is a guideline framework incorporating staging systems that provides risk stratification for cSCC. Each of these systems has a distinctive method of classifying cSCC as high-risk, which is based on a combination of various clinicopathologic features.7-10 Given the differences in these approaches, there remains a lack of uniformity for the classification and management of high-risk cSCCs following surgical excision with clear margins.10-12
