DecisionDx-SCC Test Helps Predict Outcomes in High-Risk Skin Cancer

New research suggests that a diagnostic test called DecisionDx-SCC may help doctors more accurately guide treatment for patients with high-risk cutaneous squamous cell carcinoma, the second most common form of skin cancer, according to a news release from Castle Biosciences, Inc.

The company announced the publication of two studies validating the test’s use in predicting which patients are most likely to experience local recurrence or metastasis after surgery. The findings could help physicians make more personalized treatment decisions, particularly for patients considered high-risk under National Comprehensive Cancer Network (NCCN) guidelines.

DecisionDx-SCC is a gene expression profile test that examines the activity of 40 genes within a patient’s tumor. By analyzing tumor biology rather than relying only on traditional staging, the test assigns patients into one of three categories: Class 1 (low risk), Class 2A (higher risk), or Class 2B (highest risk).

Previous research has shown that the test can predict which patients are more likely to develop metastasis or respond to adjuvant radiation therapy. The new data expand its use to also predicting local recurrence after surgery. This means the test now provides doctors with three key pieces of information: likelihood of recurrence, risk of spread and potential benefit from adjuvant radiation therapy.

DecisionDx-SCC Test Helps Identify Which Patients with High-Risk Skin Cancer May Benefit From More or Less Treatment

Although most high-risk squamous cell carcinoma cases can be successfully treated with Mohs surgery, some patients still face recurrence or spread of disease. Current staging systems, such as the American Joint Committee on Cancer and Brigham and Women’s Hospital systems, are limited in their ability to predict which patients fall into that group. This makes treatment decisions challenging; some patients may receive unnecessary additional therapy, while others at higher risk may not get the extra care they need.

“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 squamous cell carcinoma patients,” said Dr. Désirée Ratner, a Mohs micrographic surgeon and clinical professor of dermatology at NYU Grossman School of Medicine. “The ability of the test to reliably identify those patients at risk of developing local recurrence or metastasis is not only practice-changing for physicians who treat squamous cell carcinoma, but also life-changing for their patients.”

DecisionDx-SCC More Accurately Predicts Recurrence and Spread in High-Risk Skin Cancer

In one study of 414 patients with high-risk squamous cell carcinoma who had undergone Mohs surgery, DecisionDx-SCC significantly outperformed current staging systems in predicting both recurrence and metastasis. For example:

• Three-year local recurrence-free survival was 95.3% for Class 1, 85.5% for Class 2A and 71.4% for Class 2B patients.
• Metastasis-free survival rates showed a similar trend, with 97.1% for Class 1, 89.3% for Class 2A and 57.1% for Class 2B.
• Traditional staging systems did not significantly distinguish between these outcomes.

The second study surveyed 244 clinicians and found that DecisionDx-SCC results aligned with their treatment thresholds. Most recommended adjuvant radiation therapy when a patient’s recurrence or metastasis risk was 20% or higher, and surveillance imaging when risk was at least 10%. The test’s Class 2A and 2B results corresponded closely to these thresholds, supporting its role in guiding care.

“Together, these studies provide compelling support for the use of DecisionDx-SCC in clinical practice to precisely identify high-risk patients above and below established thresholds,” Castle Biosciences stated in its release. “This enables clinicians to better align treatment strategies with individual patient risk and potentially improve outcomes.”

Overall, DecisionDx-SCC focuses on tumor biology rather than population averages and aims to close a gap in current staging methods and improve decision-making for both doctors and patients.

Reference

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, by Castle Biosciences, Inc. News release; Aug. 25, 2025.

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