Castle Biosciences, Inc. announced the publication of a new multi-center performance study of its DecisionDx-SCC risk stratification test. The study, published in Dermatology and Therapy and available here, analyzed the independent performance of DecisionDx-SCC from risk factors and traditional staging systems (i.e., Brigham and Women?s Hospital (BWH) and American Joint Committee on Cancer Staging Manual 8th Edition (AJCC8) staging), and demonstrated significantly improved predictive accuracy when the test?s results were integrated with the staging systems and National Comprehensive Cancer Network® (NCCN) guidelines to guide risk-appropriate treatment pathway decisions that can improve patient outcomes. The DecisionDx-SCC test was developed and validated to improve the accuracy of metastatic risk prediction for patients with high-risk SCC, classifying patients as low (Class 1), higher (Class 2A) or highest risk (Class 2B) of regional or distant metastasis within three years based on the gene expression profile of their tumor.

The data in this study support use of the test?s results in the clinical management of high-risk SCCs as they can provide impactful risk-stratification to guide risk-appropriate treatment pathway decisions, such as the use of nodal assessment (i.e., imaging) and adjuvant radiation therapy (ART). The goal of this study was to present an independent validation of the DecisionDx-SCC test in a novel performance cohort (n=534) and then merge it with the test?s initial independent validation cohort (n=420) to evaluate the performance of the test in providing independent prognostic value to risk classification systems, individual clinicopathologic risk factors and clinically relevant patient populations.1-2 In the study, DecisionDx-SCC demonstrated statistically significant risk-stratification of patients with high-risk SCC (p<0.001); 3-year metastasis-free survival rates were 94.1%, 81.1% and 56.8% for patients with Class 1, Class 2A and Class 2B test results, respectively. The entire population had 3-year metastasis-free survival of 87.5%.

DecisionDx-SCC also provided significant and clinically actionable risk stratification in various patient subgroups, including NCCN high and very high-risk, lower-stage BWH tumors and Medicare-eligible patients, further stratifying risk to help guide important treatment decisions for these patients. Generally, treatment pathways for patients with SCC are based on population-based estimates of risk, informed by guidelines and traditional staging systems (AJCC8 and BWH) which use various clinicopathological risk factors to predict a patient?s risk of metastasis. Multivariate analyses demonstrated that DecisionDx-SCC Class 2A and 2B test results were independent and significant predictors of metastasis when evaluated in the context of NCCN risk stratification, AJCC8 and BWH staging, and various clinicopathologic risk factors, such as immunosuppression, poor differentiation and tumor thickness (>6mm) (p<0.001).

Importantly, integrating DecisionDx-SCC with individual clinicopathologic risk factors or risk classification systems (AJCC8 and BWH) significantly improved the accuracy for prediction of metastatic events (ANOVA for model deviance, p<0.0001 for all models). These data support the use of DecisionDx-SCC test results, informed by a patient?s tumor biology, to guide personalised patient treatment decisions aligned to a patient?s risk of metastasis over three years. These decisions could include risk-aligned reductions in treatment intensity for patients with low risk (Class 1) test results and intensified treatment, such as consideration of ART, for patients at a higher risk of experiencing metastasis (Class 2A and 2B).