Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically...

Area of Science:

• Oncology
• Genomics
• Biomarkers

Background:

• Cutaneous squamous cell carcinoma (cSCC) risk stratification is crucial for patient management.
• The 40-gene expression profile (40-GEP) test is a validated tool for assessing metastasis risk in cSCC.
• High-risk clinicopathologic features necessitate accurate risk stratification.

Purpose of the Study:

• To evaluate the 40-GEP test's risk stratification performance in a large cSCC cohort.
• To assess 40-GEP performance in specific subgroups, including NCCN high/very-high risk and early-stage tumors.
• To determine if 40-GEP improves risk prediction accuracy compared to existing systems.

Main Methods:

• Multicenter study involving 897 patients with cSCC.
• Kaplan-Meier analysis to assess 40-GEP Class 1, 2A, and 2B risk profiles.
• Nested Cox regression models to compare clinicopathologic systems with and without 40-GEP integration.

Main Results:

• 40-GEP Class 1, 2A, and 2B groups showed significantly different metastatic risk profiles (p < 0.0001).
• Integration of 40-GEP significantly improved the accuracy of predicting metastatic events across various risk classification systems (p < 0.0001).
• Improved predictive accuracy was observed when combining 40-GEP with NCCN and AJCC staging systems.

Conclusions:

• The 40-GEP test provides accurate and independent stratification of metastatic risk in cSCC.
• Integrating 40-GEP enhances the predictive accuracy of existing risk classification systems.
• The 40-GEP test facilitates more personalized and risk-aligned patient management decisions by incorporating tumor biology.