Study Shows Prognostic Value of 40-GEP in Advanced cSCC
Key Takeaways
The 40-GEP test improves metastatic risk stratification in cutaneous squamous cell carcinoma (cSCC) patients already classified as high or very-high risk per NCCN guidelines.
Stratification using both Brigham and Women's Hospital staging and 40-GEP significantly differentiates 3-year metastasis-free survival outcomes.
Researchers said the findings support the integration of molecular profiling in routine risk assessment and clinical decision-making for cSCC.
A new multi-institutional study indicates that a 40-gene expression profile (40-GEP) test with traditional staging enhances risk stratification for cutaneous squamous cell carcinoma (cSCC), even among patients already categorized as high- or very-high-risk using National Comprehensive Cancer Network® (NCCN) guidelines.
Researchers for the study evaluated 1,412 patients with primary cSCC from a combined cohort that included a previously published dataset and new cases from Brigham and Women’s Hospital and the Cleveland Clinic. All participants had at least one NCCN-defined high-risk feature such as tumor diameter ≥2 cm, poor differentiation, perineural invasion, or subcutaneous fat involvement. Patients who had previously received adjuvant radiation were excluded.
The study authors used Kaplan-Meier survival analysis and Cox regression to examine 3-year regional/distant metastasis-free survival (MFS), comparing standard Brigham and Women’s Hospital (BWH) T-staging with or without the addition of 40-GEP classifications (Class 1, 2A, or 2B).
The 40-GEP test stratified metastatic risk in both NCCN High-Risk and Very-High-Risk groups. Within the NCCN High-Risk group (n=842), adding 40-GEP to BWH T1/T2a staging showed significant variance in 3-year survival (97.4% in Class 1, 91.2% in Class 2A, and only 71.4% in Class 2B patients). In the Very-High-Risk cohort (n=506), Class 2B patients with high BWH stage had a lower 3-year survival of 46.8% vs. 81.6% in Class 1 patients with the same BWH stage.
“Incorporation of the 40-GEP with BWH T-staging significantly improved the accuracy of metastatic risk stratification in both NCCN High- and Very-High-Risk subgroups of patients,” the authors wrote. “Integrating the 40-GEP with BWH staging, even within NCCN High or Very-High-Risk profiles, refines risk stratification and supports more accurate clinical decisions, improving personalized care.”
Source: Ruiz E, Brito K, Kam E, et al. Metastasis-free survival prediction with the 40-gene expression profile test in patients with cutaneous squamous cell carcinoma risk stratified according to the National Comprehensive Cancer Network Guidelines®. Presented: National Comprehensive Cancer Network® (NCCN) Annual Conference; March 28-30, 2025; Orlando, FL.