New Studies Expand Clinical Role of DecisionDx-SCC in High-Risk cSCC

Castle Biosciences, Inc. announced today the publication of 2 studies expanding the evidence base for its DecisionDx-SCC gene expression profile (40-GEP) test in patients with National Comprehensive Cancer Network (NCCN) high-risk cutaneous squamous cell carcinoma (SCC).¹ DecisionDx-SCC is designed to stratify risk by evaluating tumor biology, providing individualized predictions of metastasis, response to adjuvant radiation therapy (ART), and now, local recurrence.²

Expanding Clinical Applications

The first study demonstrated that DecisionDx-SCC can predict local recurrence in NCCN high-risk SCC patients who have undergone Mohs resection. This represents a third validated application for the test, which was previously established as predictive for metastatic risk and likelihood of benefit from ART. According to investigators, this expanded utility may provide a more comprehensive view of patient-specific risk following surgery, potentially informing more precise treatment pathways.

In parallel, the second study surveyed clinicians on how they use DecisionDx-SCC results in management decisions. Findings showed that the test meaningfully influenced recommendations for ART and surveillance imaging, offering clinicians actionable data to escalate or de-escalate care in line with individualized risk.

Addressing Gaps in Current Risk Stratification

Although the majority of patients with NCCN high-risk SCC achieve favorable outcomes with Mohs surgery, a subset experiences recurrence or metastasis. Current staging systems, including the American Joint Committee on Cancer (AJCC) version 8 and Brigham and Women’s Hospital (BWH) T-staging, provide limited ability to stratify patients by recurrence or metastatic potential. As a result, clinicians often struggle to balance overtreatment of low-risk patients with undertreatment of those at highest risk.

By incorporating tumor biology, DecisionDx-SCC seeks to overcome these limitations and refine treatment recommendations. “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, MD, Mohs micrographic surgeon and clinical professor of dermatology at the NYU Grossman School of Medicine in New York, in the news release. “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.”¹

Study Outcomes

In the first study, 414 patients with NCCN high-risk SCC and negative margins following Mohs surgery were evaluated. DecisionDx-SCC significantly stratified both local recurrence and metastasis-free survival (MFS). Three-year local recurrence-free survival (LRFS) decreased across risk groups:

• 95.3% for Class 1 (low risk)
• 85.5% for Class 2A (higher risk)
• 71.4% for Class 2B (highest risk) (P=0.001)

Similarly, 3-year MFS declined across classes at 97.1%, 89.3%, and 57.1% respectively (P<0.001). In contrast, AJCC and BWH staging systems did not significantly stratify LRFS or MFS.

Multivariate analysis further demonstrated that DecisionDx-SCC Class 2A and 2B results, immunosuppression, and perineural invasion were all significant predictors of recurrence. The inclusion of DecisionDx-SCC results improved predictive accuracy when compared with clinicopathologic factors alone.

The clinician survey (n=244) provided complementary insights into how these test results affect decision-making. Most respondents recommended ART for patients with ≥20% recurrence or metastatic risk, while surveillance imaging was generally suggested at ≥10% risk. DecisionDx-SCC Class 2A and 2B results aligned closely with these thresholds, with clinicians identifying Class 2B results as a key driver in recommending ART.

Implications for Clinical Practice

Together, the company stated these findings suggest that DecisionDx-SCC may help clinicians more precisely identify NCCN high-risk SCC patients most likely to experience recurrence or metastasis. By distinguishing between patients who may benefit from escalated care—such as ART and enhanced surveillance—and those who may not, the test has the potential to reduce both overtreatment and undertreatment.

While additional real-world data and longer-term validation will further clarify its role, the growing body of evidence positions DecisionDx-SCC as a potentially valuable adjunct to existing clinicopathologic risk stratification tools. By providing biologically based, individualized risk assessments, the test may support more nuanced decision-making in post-surgical management of high-risk SCC.

References

1. New evidence published supporting use of DecisionDx-SCC test in guiding and improving treatment pathway decisions in NCCN high-risk cutaneous squamous cell carcinoma. News release. Castle Biosciences. August 25, 2025. Accessed August 25, 2025. https://ir.castlebiosciences.com/news/news-details/2025/New-Evidence-Published-Supporting-Use-of-DecisionDx-SCC-Test-in-Guiding-and-Improving-Treatment-Pathway-Decisions-in-NCCN-High-Risk-Cutaneous-Squamous-Cell-Carcinoma/default.aspx
2. FDA grants breakthrough device designation to Castle Biosciences’ DecisionDx-melanoma test. News release. Castle Biosciences. July 23, 2025. Accessed August 25, 2025. https://www.biospace.com/press-releases/fda-grants-breakthrough-device-designation-to-castle-biosciences-decisiondx-melanoma-test