Castle Biosciences, Inc. announced the publication of an expert consensus article in the Journal of Clinical and Aesthetic Dermatology (JCAD)related to the utility of its DecisionDx-SCC test in clinical decision-making regarding the use of ART. The consensus guidelines outline a recommended risk-based workflow that integrates DecisionDx-SCC and AJCC8 staging into current National Comprehensive Cancer Network® (NCCN) guidelines to improve precision in ART recommendations based on which patients are at the highest risk for metastasis and most likely to benefit from treatment. The expert panel convened in June 2023 to review validation and real-world data for the DecisionDx-SCC test and to discuss their experiences, rationales and scenarios in which they have used the test to improve risk stratification and more accurately identify SCC patients at high risk of metastasis who may benefit from ART.

The panel identified gaps in current clinical practice where the DecisionDx-SCC test has utility in guiding treatment decisions, including its use regarding: Escalation of care for lower-stage patients with high-risk tumors, De-escalation of care for patients for whom the risks of ART may outweigh the benefits, and Decision-making regarding elective radiation to the nodal basin. Based on these gaps, the panel developed risk-based clinical recommendations and a workflow for ART referral in patients with SCC, which can be viewed in the JCAD article. The workflow integrates DecisionDx-SCC testing, which analyzes a patient?s tumor biology to independently predict risk of nodal or distant metastasis, and AJCC8 staging, which is based on a patient?s clinicopathologic risk factors, into current NCCN guidelines with a goal of improving precision in ART recommendations in the SCC patient population.

Specific consensus recommendations and statements outlined in the article include the following: A DecisionDx-SCC Class 2A or 2B result, indicating a higher or highest risk of metastasis, in each AJCC8 tumor stage serves as a high- or very high-risk feature for consideration in recommending ART. The increased metastatic risk conferred by a Class 2A or 2B result in multivariate analysis (hazard ratio=2.3, p=0.013; and hazard ratio=6.9, p<0.001, respectively) is similar or higher than that conferred by other high-risk clinicopathologic features, including PNI and poor differentiation. Patients at the highest risk of metastasis, as indicated by a DecisionDx-SCC Class 2B test result, should be referred to radiation oncology with a recommendation for a multidisciplinary tumor board discussion.

In nuanced discussions where the risks associated with ART may outweigh the benefits, the additional information provided by the DecisionDx-SCC test can assist in personalized decision-making. The DecisionDx-SCC test can help radiation oncologists determine a more precise risk-benefit ratio for elective nodal radiation. The panel recommended stronger consideration of elective nodal radiation for a DecisionDx-SCC Class 2B tumor, given the dramatically increased risk of nodal metastasis.

Overall, the panel agreed the DecisionDx-SCC test provides independent risk stratification that, when combined with traditional staging and management guidelines, enhances the clinical picture, allowing clinicians to more accurately identify SCC patients who are most likely to benefit from ART, as well as lower-risk patients who would benefit less from treatment. In a validation study of the DecisionDx-SCC test by Wysong et al., metastatic risk prediction of AJCC8 and BWH staging systems was significantly improved when DecisionDx-SCC test results were included. As supported by the consensus article, the objective, independent risk stratification provided by the test can improve precision in multidisciplinary treatment recommendations, such as the use of ART, which could save the U.S. healthcare system hundreds of millions of dollars through more appropriate use of the treatment.