Implications of a prognostic 40-gene expression profile (40-GEP) test for high-risk cutaneous squamous cell carcinoma (cSCC) on staging-based risk assessment and adjuvant therapy trial design.

Abstract

e22091 Background: Deaths due to cSCC are expected to exceed melanoma-specific deaths. With the demonstration of effective therapies for advanced cSCC, and as treatment of patients in the adjuvant setting is considered, accurate prognosis is critical. For improved identification of ‘high-risk’ patients, with biologically aggressive disease capable of metastasis, a prognostic 40-gene expression profile (40-GEP) test was validated using an independent cohort of patients with high-risk cSCC and known clinical outcomes. The test identified three groups with increasing metastasis risk profiles: Class 1 (low risk), Class 2A (high risk), and Class 2B (highest risk) having metastasis rates of 8.9%, 20.4%, and 60%, respectively. Multivariable analysis demonstrated prognostic efficacy of the 40-GEP test alone and in combination with clinicopathological staging systems. This study evaluated risk stratification with concurrent consideration of the 40-GEP result and the Brigham and Women’s Hospital (BWH) stage. The primary objective was evaluation of the potential impact of the 40-GEP on adjuvant clinical trial design. Methods: To determine if a 40-GEP Class 2B result could optimize clinical trial accrual, metastasis rates of BWH high-risk T stage patients (T2b-T3) alone and in combination with 40-GEP results from the validation cohort were used for two-arm trial sample size calculations. Results: Metastasis rates for cases with T2b-T3 tumors increased from 35.1% to 71.4% when selecting for T2b-T3 cases with a 40-GEP Class 2B result. To provide 80% power to detect hazard ratio of 0.6 with 3 years of follow-up (alpha = 0.05), in line with improvement rates by addition of radiation to surgery, 434 T2b-T3 patients are required for randomization. However, sample size could be reduced by 51% to 214 patients by focusing enrollment on T2b-T3 patients with a 40-GEP Class 2B result. Conclusions: These results support the incorporation of the 40-GEP test into selection processes for patients with T2b-T3 tumors who are at the highest risk for metastasis and appropriate for adjuvant clinical trials.