DecisionDx-SCC Improves Risk Stratification in High-Risk CSCC

New evidence published in a pair of studies supports the use of a gene expression profile test, DecisionDx-SCC, in guiding and improving treatment pathway decisions for patients with high-risk cutaneous squamous cell carcinoma (cSCC).¹

The findings, published in 2 studies in Skin: the Journal of Cutaneous Medicine, demonstrate the test's ability to provide individualized risk predictions for local recurrence and metastasis, outperforming conventional staging systems. The test's actionable results align with clinical thresholds for recommending adjuvant radiation therapy and surveillance imaging, offering a valuable tool for clinicians aiming to optimize patient care and avoid both over- and under-treatment.

“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 and investigator on one of the studies, in a press 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.”

The gene expression profile test analyzes the gene expression of 40 specific genes to provide a patient-specific risk score. This score stratifies patients into three risk classes: Class 1 (low risk), Class 2A (higher risk), and Class 2B (highest risk). This stratification provides a more nuanced approach to risk assessment than traditional anatomical staging systems like the American Joint Committee on Cancer (AJCC) version 8 and the Brigham and Women's Hospital (BWH) T-staging system. The studies suggest that reliance on these older systems may lead to suboptimal treatment decisions, as they can misclassify a significant number of patients, potentially leading to unnecessary aggressive therapy or inadequate management.

One of the studies specifically evaluated the test's performance in predicting local recurrence and metastasis in patients who had undergone Mohs micrographic surgery.² The results showed a clear correlation between the test's risk classes and patient outcomes. Patients in Class 1 had a significantly lower risk of recurrence and metastasis, while those in Class 2B exhibited a progressively higher risk and a corresponding decrease in disease-free survival. This finding is particularly notable as it adds the prediction of local recurrence to the test's established ability to predict metastatic risk, providing clinicians with a more comprehensive tool for postsurgical risk assessment.

A separate clinician survey study further supported the clinical utility of the test.³ The survey, which polled clinicians on their treatment recommendations, found a strong alignment between the test's risk scores and thresholds for two critical treatment decisions: adjuvant radiation therapy (ART) and surveillance imaging. Clinicians reported that they were most likely to recommend ART for patients with a risk of local recurrence or metastasis of 20% or higher. They also indicated a threshold of 10% or higher for recommending intensive surveillance imaging. The gene expression profile test’s Class 2A and Class 2B results correlated directly with these established clinical thresholds, providing objective, data-driven support for treatment planning.

The test’s ability to pinpoint high-risk patients allows for the targeted application of ART, which is associated with significant morbidity, to only those patients most likely to benefit. Conversely, it helps identify patients who may be safely managed with less aggressive surveillance, reducing the burden of care and potential side effects from unnecessary treatment.

By providing an objective, molecular-based risk assessment, the test empowers clinicians to make more informed decisions regarding the intensity of treatment and follow-up care.

FAQs

What is DecisionDx-SCC and how does it improve risk stratification for patients with high-risk cutaneous squamous cell carcinoma (cSCC)?

DecisionDx-SCC is a gene expression profile test designed to provide individualized risk predictions for local recurrence and metastasis in patients with high-risk cSCC. It analyzes the expression of 40 specific genes to generate a patient-specific risk score, stratifying patients into 3 classes: Class 1 (low risk), Class 2A (moderate risk), and Class 2B (highest risk). This molecular-based approach offers a more nuanced risk assessment compared to traditional anatomical staging systems like AJCC version 8 and BWH T-staging, which can sometimes misclassify patients. By providing more precise risk predictions, DecisionDx-SCC helps clinicians optimize treatment pathway decisions, avoiding both over- and under-treatment.

How does DecisionDx-SCC compare to conventional staging systems for cSCC?

Traditional systems can lead to suboptimal treatment decisions by misclassifying a notable number of patients, potentially resulting in unnecessary aggressive therapy or inadequate management. In contrast, DecisionDx-SCC provides individualized risk predictions that are more accurate, allowing for risk-aligned escalation or deescalation of care. The test's ability to reliably identify patients at risk of local recurrence or metastasis is considered practice-changing for physicians and life-changing for patients.

What specific outcomes does DecisionDx-SCC predict, and how does this benefit postsurgical assessment?

DecisionDx-SCC predicts both local recurrence and metastatic risk in patients, including those who have undergone Mohs micrographic surgery. Studies have shown a clear correlation between the test's risk classes and patient outcomes: Class 1 patients have a significantly lower risk of recurrence and metastasis, while Class 2B patients exhibit a progressively higher risk and a corresponding decrease in disease-free survival. This comprehensive predictive capability, which includes the prediction of local recurrence in addition to metastatic risk, provides clinicians with a more robust tool for post-surgical risk assessment, aiding in more informed management decisions.

What are the benefits of using DecisionDx-SCC for guiding adjuvant radiation therapy (ART) decisions?

The DecisionDx-SCC test helps clinicians make more targeted decisions regarding adjuvant radiation therapy (ART). ART is associated with significant morbidity, and the test's ability to pinpoint high-risk patients (specifically those in Class 2A and Class 2B, who meet or exceed the 20% risk threshold for ART) ensures that this aggressive therapy is applied only to those most likely to benefit. Conversely, it helps identify patients who may be safely managed with less aggressive surveillance, thereby reducing the burden of care and potential side effects from unnecessary ART. This ensures that treatment is aligned with the patient's actual risk profile.

This article was generated with assistance from Google Gemini and NotebookLM. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

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 26, 2025. https://tinyurl.com/338cafyu

2. Ratner D, Arron ST, Kim YJ, et al. The 40-Gene Expression Profile Test Identifies Patients with National Comprehensive Cancer Network High-Risk Cutaneous Squamous Cell Carcinoma at High Risk of Poor Outcomes to Inform Management Decisions. J of Skin. 2025;9(4):2426-2443. doi:10.25251/mvr2rn83

3. Shah M, Zakria D, Rogers JH, et al. Actionable Risk Thresholds for Adjuvant Radiation Therapy and Surveillance Imaging in High-Risk Cutaneous Squamous Cell Carcinoma. J of Skin. 2025;9(4):2444-2461. doi:10.25251/83v2hr07