Castle Biosciences Expands DecisionDx-SCC Test to Predict Local Recurrence in High-Risk Skin Cancer Patients

Author: Benzinga Newsdesk | August 25, 2025 07:14am

Castle Biosciences, Inc. (NASDAQ:CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of two new studies related to its DecisionDx-SCC test, adding to its validated uses for patients with high-risk cutaneous squamous cell carcinoma (SCC).1,2 DecisionDx-SCC is a gene expression profile test (40-GEP) designed to use a patient's tumor biology to predict individual risk of metastasis as well as response to adjuvant radiation therapy (ART).

The first study represents an expanded clinical use milestone, demonstrating that DecisionDx-SCC predicts local recurrence in patients classified as high-risk by National Comprehensive Cancer Network (NCCN) guidelines who have undergone Mohs resection, thereby adding a third use to the test's existing capabilities.¹ The test has now been shown to predict individual risk of metastasis, response to ART and individual risk of local recurrence, providing comprehensive results to support tailored post-surgical management and treatment pathway recommendations for patients with SCC. The second study shares results from a clinician survey, affirming the impact of the test's results in guiding these recommendations, specifically the use of ART and surveillance imaging, by providing actionable decision points based on individual patient risk.2

"These new data indicate that DecisionDx-SCC test results provide individualized risk predictions that doctors can use to guide risk-aligned escalation or de-escalation of care in their NCCN high-risk SCC patients," said Désirée Ratner, M.D., Mohs micrographic surgeon and clinical professor of dermatology at the NYU Grossman School of Medicine in New York. "The ability of the test to reliably identify those patients with NCCN high-risk SCC at risk of developing local recurrence or metastasis is not only practice-changing for physicians who treat SCC, but also life-changing for their patients."

While most patients with NCCN high-risk SCC can be treated successfully with Mohs surgery, a subset of these patients will experience local recurrence and/or metastasis. Current staging systems, including American Joint Committee on Cancer (AJCC) version 8 staging and Brigham and Women's Hospital (BWH) T-staging, inadequately identify which patients are at highest risk for poor outcomes, creating a critical clinical need for better risk stratification tools. This limitation makes it challenging for clinicians to determine optimal treatment strategies, leading to over-treatment of low-risk patients and under-treatment of high-risk patients who may benefit from escalated approaches such as ART or enhanced post-surgical surveillance. These two new studies contribute to growing evidence that DecisionDx-SCC has the potential to address this clinical gap by enabling risk-aligned treatment decisions based on a patient's individual tumor biology rather than population-based staging criteria alone.

Key highlights of the studies include the following:

• Among 414 NCCN high-risk SCC patients with negative margins following Mohs surgery, DecisionDx-SCC significantly stratified both local recurrence and metastatic risk. Three-year survival rates decreased progressively across risk classes: local recurrence-free survival (LRFS) was 95.3% (Class 1, low risk) vs. 85.5% (Class 2A, higher risk) vs. 71.4% (Class 2B, highest risk), P=0.001; metastasis-free survival (MFS) was 97.1% vs. 89.3% vs. 57.1%, P<0.001.
• In contrast, BWH and AJCC staging systems failed to significantly stratify LRFS (log-rank, P=0.6) and MFS (log-rank, P=0.8).1
• DecisionDx-SCC test results (Class 2A and 2B), immunosuppression and perineural invasion were significant predictors of local recurrence, with hazard ratios of 2.6, 5.3, 2.3 and 3.7, respectively (all P<0.05). When combined with these two clinicopathologic factors which have a well-established association to a high risk of metastasis, DecisionDx-SCC demonstrated significant improvement in predictive accuracy compared to the clinicopathologic factors alone (likelihood ratio: 21.65 vs. 12.27).¹
• The 244 clinicians surveyed in the second study most often recommended ART for patients with ≥20% risk of local recurrence or metastasis, and surveillance imaging for patients with ≥10% risk of metastasis.2
• Accordingly, DecisionDx-SCC Class 2A results accurately predicted risk above the 10% threshold where most clinicians would recommend surveillance imaging and consider ART, while Class 2B results predicted risk above the 20% threshold where most clinicians would recommend proceeding with ART.1,2
• Clinicians who use DecisionDx-SCC reported a Class 2B test result to be among the most important risk factors they consider when making management decisions for ART.2

Together, these studies provide compelling support for the use of DecisionDx-SCC in clinical practice to precisely identify NCCN high-risk patients above and below established risk thresholds, enabling clinicians to better align treatment strategies with individual patient risk and potentially improving outcomes within established NCCN treatment pathways.

Posted In: CSTL