DecisionDx-SCC shows enhanced performance with the integration of select clinicopathologic risk factors, providing a more precise result to support risk-aligned patient management

DecisionDx-SCC's Class 1A (low risk) result demonstrated a 97.3% negative predictive value, supporting confidence in de-escalation decisions, while its Class 2B (highest risk) result identified patients most likely to benefit from adjuvant radiation therapy

FRIENDSWOOD, Texas, Sept. 9, 2026 /PRNewswire/ -- Castle Biosciences, Inc. (NASDAQ:CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of a multi-center study in the Journal of the American Academy of Dermatology (JAAD) validating the integrated DecisionDx-SCC test result (i40-GEP) for patients with high-risk cutaneous squamous cell carcinoma (SCC).¹

DecisionDx-SCC analyzes 40 genes to provide results related to prognosis and response to adjuvant radiation therapy (ART) based on an individual patient's tumor biology. The enhanced algorithm integrates the molecular data with five clinicopathologic risk factors (immunosuppression, tumor diameter, histological differentiation, perineural invasion and anatomic site) using optimized nested predictive models. This integrated approach provides a comprehensive assessment of metastatic risk, local recurrence risk and likelihood of benefit from ART. The study published in JAAD showed that the test results can shift or stratify patients across clinically actionable risk thresholds, supporting risk-aligned decisions regarding patient follow-up, surveillance imaging, multidisciplinary referral and ART.

"Managing high-risk SCC patients can be challenging because clinicopathologic staging isn't always precise enough to confidently tailor patients' treatment intensity to their individual level of risk," said lead study author Désirée Ratner, M.D., board-certified dermatologist and Mohs micrographic surgeon, and clinical professor of dermatology at NYU Grossman School of Medicine in New York. "The ability to more precisely distinguish which patients require less intensive management from those who would benefit from additional treatment can help reduce uncertainty for both patients and physicians. This study showed that the DecisionDx-SCC integrated test result, which evaluates patients' tumor biology in combination with their clinicopathologic risk factors, can provide improved, clinically actionable information to support informed discussions about the most appropriate, risk aligned management approach."

The study, titled "Validation of the integrated 40-gene expression profile (i40-GEP) which provides prognostic and adjuvant radiation benefit for high-risk cutaneous squamous cell carcinoma," evaluated the enhanced DecisionDx-SCC algorithm in an independent validation cohort of 572 patients with high-risk SCC.

Key study findings include:

DecisionDx-SCC significantly stratified patients by metastatic and local recurrence risk (p<0.0001 for both). In multivariable analysis, the test results provided significant predictive information beyond individual clinicopathologic risk factors for both outcomes.
Nearly half of patients in the cohort (44.6%) were classified by the i40-GEP test as Class 1A (low risk). This result demonstrated a 97.3% negative predictive value (NPV) and may support greater confidence when considering de-escalation of care in low-risk patients.
The refined algorithm classified 12.9% of patients as Class 2B (highest risk). These patients had a three-year metastasis-free survival rate of 66.2%, compared with 97.3% for patients with Class 1A (low risk) test results. In multivariable analysis, Class 2B patients were 10.7 times more likely to develop metastasis than Class 1A patients (p<0.001), demonstrating strong separation between the test's lowest- and highest-risk results.
In addition, the Class 2B result identified patients with a high likelihood of benefitting from ART. Patients with Class 2B test results who were treated with ART had an approximately 50% lower median metastatic progression rate at five years than those who did not receive ART. Class 2B ART-treated patients also showed significantly delayed disease progression with decreased acceleration of events compared to Class 2B patients who did not receive ART (p<0.01). No significant difference was observed between ART-treated and untreated patients with Class 2A (high risk) test results.
DecisionDx-SCC demonstrated greater accuracy in predicting metastatic risk than National Comprehensive Cancer Network (NCCN) risk groups and Brigham and Women's Hospital (BWH) staging.

"Continuous innovation at Castle means building on well-established tests as evidence and clinical needs evolve," said Rebecca Critchley-Thorne, Ph.D., vice president, research and development, at Castle Biosciences. "By preserving DecisionDx-SCC's established 40-gene foundation while refining its algorithm to integrate clinicopathologic factors, we can provide more precise, clinically actionable information while maintaining the test's core molecular profile. The study published in JAAD validates these refinements designed to increase confidence in lower-risk results, provide greater clarity for intermediate-risk patients and identify the highest-risk patients most likely to benefit from ART."

About DecisionDx-SCC

DecisionDx-SCC is a gene expression profile (GEP) test that integrates tumor biology and key clinicopathologic risk factors to deliver a refined, personalized risk assessment for patients with cutaneous squamous cell carcinoma (SCC) and one or more high-risk factors. The test provides a patient's individual risk of metastasis and local recurrence, as well as likelihood of benefit from adjuvant radiation therapy (ART). This clinically actionable information is designed to help guide risk-aligned management decisions, including surveillance, imaging, multidisciplinary consultation and consideration of ART.

DecisionDx-SCC has been clinically validated in a multicenter study of patients with localized high-risk cutaneous SCC, in which it was shown to be the strongest predictor of metastasis and local recurrence compared with individual clinicopathologic risk factors and to outperform traditional risk assessment systems. The study adds to a broader evidence base of 20 peer-reviewed publications supporting the test's clinical performance and role in informing individualized patient management. Learn more at DecisionDx-SCC Overview.

About Castle Biosciences

Castle Biosciences (NASDAQ:CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. With a primary focus in dermatologic and gastroenterological disease, we develop personalized, clinically actionable solutions that help improve disease management and patient outcomes.

We put people first—empowering patients and clinicians and informing care decisions through rigorous science and advanced molecular tests that support more confident treatment planning. To learn more, visit www.CastleBiosciences.com and connect with us on LinkedIn, Instagram, Facebook and X. 

DecisionDx-Melanoma, DecisionDx-CMSeq, i31-SLNB, i31-ROR, DecisionDx-SCC, MyPath Melanoma, AdvanceAD-Tx, TissueCypher, Esopredict, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the "safe harbor" created by those sections. These forward-looking statements include, but are not limited to, statements concerning the ability of DecisionDx-SCC to: (i) improve risk stratification and strengthen treatment guidance; (ii) provide more precise and actionable information; (iii) reduce uncertainty in the care journey and support greater confidence when considering de-escalation of management for lower-risk patients; (iv) provide clarity for intermediate-risk patients; (v) identify highest-risk patients who are most likely to benefit from ART; and (vi) inform personalized, risk-aligned decisions involving follow-up, surveillance imaging, multidisciplinary consultation and ART. The words "can," "designed," "may" and similar expressions are intended to identify forward intentions or expectations, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause actual results to differ from the forward-looking statements, including, without limitation: subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results obtained in these studies; actual application of our tests may not provide the aforementioned benefits to certain patients; and the risks set forth under the heading "Risk Factors" in our Annual Report on Form 10-K for the year ended Dec. 31, 2025, our subsequent Quarterly Reports on Form 10-Q and our other filings with the Securities and Exchange Commission. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update them, except as may be required by law.

Ratner D, Singh G, Rizzo JM, et al. Validation of the integrated 40-gene expression profile (i40-GEP) which provides prognostic and adjuvant radiation benefit for high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol. Published online August 24, 2026. Accessed August 25, 2026. https://www.jaad.org/article/S0190-9622(26)03397-9/fulltext

Investor Contact:

Camilla Zuckero

czuckero@castlebiosciences.com

Media Contact:

Allison Marshall

amarshall@castlebiosciences.com

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SOURCE Castle Biosciences, Inc.