Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients

Dermatology and Therapy
Open Access

Clinical Summary

View source

What was studied

A multicenter performance study across 58 sites assessed whether a 40‑gene expression profile (40‑GEP) stratifies risk of regional or distant metastasis in high‑risk cutaneous squamous cell carcinoma, including subgroups (NCCN high/very‑high risk, BWH T1/T2a, and patients >65 years). The cohort included 897 patients; Kaplan–Meier and nested Cox models compared clinicopathologic systems alone versus with 40‑GEP added.

Key findings

Metastatic risk differed across 40‑GEP Classes 1, 2A, and 2B (p<0.0001), and adding 40‑GEP to clinicopathologic factors or staging systems (BWH, AJCC8, NCCN) improved prediction accuracy for metastasis (ANOVA p<0.0001 for all models).

Clinical implications

In high‑risk cSCC, integrating 40‑GEP results with BWH/AJCC8/NCCN staging improves metastatic risk stratification, supporting more risk‑aligned management decisions.