AT A GLANCE

New evidence shows DecisionDx-SCC outperforms AJCC and BWH staging in predicting recurrence and metastasis in high-risk cutaneous SCC, enabling more precise, risk-aligned treatment strategies.

Two newly published studies expand the evidence base for DecisionDx®-SCC, a 40-gene expression profile (40-GEP) assay designed to refine risk stratification in patients with high-risk cutaneous squamous cell carcinoma (SCC). Current staging systems, including AJCC-8 and Brigham and Women’s Hospital (BWH) classifications, often fail to reliably distinguish which patients face a higher likelihood of local recurrence or metastasis, leaving clinicians with limited tools to balance escalation versus de-escalation of care.

The first study evaluated 414 patients with NCCN high-risk SCC who underwent Mohs resection with negative margins. DecisionDx-SCC stratified patients into distinct recurrence- and metastasis-free survival categories, with marked differences across risk groups: 3-year local recurrence-free survival was 95.3% for Class 1 (low risk), 85.5% for Class 2A (higher risk), and 71.4% for Class 2B (highest risk). Similarly, metastasis-free survival rates were 97.1%, 89.3%, and 57.1%, respectively. Neither AJCC nor BWH staging achieved comparable prognostic discrimination. Moreover, the test provided incremental predictive accuracy when combined with established clinicopathologic risk factors, such as immunosuppression and perineural invasion.

The second study, a survey of 244 clinicians, confirmed that DecisionDx-SCC results influence treatment decisions. Most clinicians recommended adjuvant radiation therapy (ART) when risk exceeded 20% and surveillance imaging at the 10% threshold—benchmarks that align closely with Class 2A and 2B results. Physicians reported that Class 2B findings were among the most important factors driving ART recommendations.

Together, these findings position DecisionDx-SCC as a clinically actionable tool that integrates tumor biology into risk assessment. By moving beyond population-based staging, the test may improve risk-aligned management strategies, reduce unnecessary interventions in low-risk patients, and ensure timely escalation of care for those at greatest risk of recurrence or metastasis.