The consensus guidelines were drafted by a multidisciplinary panel of radiation oncologists and dermatologists/Mohs micrographic surgeons with expertise in cutaneous squamous cell carcinoma (SCC) management; they provide a recommended framework for using DecisionDx-SCC testing with American Joint Committee on Cancer 8^th Edition (AJCC8) staging to guide decisions regarding the use of adjuvant radiation therapy (ART) in patients with high-risk SCC to control disease progression¹

Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of an expert consensus article in the Journal of Clinical and Aesthetic Dermatology (JCAD) related to the utility of its DecisionDx-SCC test in clinical decision-making regarding the use of ART.² The consensus guidelines outline a recommended risk-based workflow that integrates DecisionDx-SCC and AJCC8 staging into current National Comprehensive Cancer Network® (NCCN) guidelines to improve precision in ART recommendations based on which patients are at the highest risk for metastasis and most likely to benefit from treatment.

“ART is recommended by evidence-based guidelines to reduce the risk of recurrence in patients with high-risk SCC,” said Ramesh Gopal, M.D., Ph.D., lead author, radiation oncologist and associate professor of radiation oncology at the New Mexico Comprehensive Cancer Center in Albuquerque, New Mexico. “While the presence of perineural invasion (PNI) will typically trigger a conversation about whether to consider ART, the guidelines vary in their interpretation of which SCC patients should be considered for the treatment, which can carry a risk of side-effects for the patient and costs for our healthcare system.”

The expert panel convened in June 2023 to review validation and real-world data for the DecisionDx-SCC test and to discuss their experiences, rationales and scenarios in which they have used the test to improve risk stratification and more accurately identify SCC patients at high risk of metastasis who may benefit from ART. The panel identified gaps in current clinical practice where the DecisionDx-SCC test has utility in guiding treatment decisions, including its use regarding:

• Escalation of care for lower-stage patients with high-risk tumors,
• De-escalation of care for patients for whom the risks of ART may outweigh the benefits, and
• Decision-making regarding elective radiation to the nodal basin.

Based on these gaps, the panel developed risk-based clinical recommendations and a workflow for ART referral in patients with SCC, which can be viewed in the JCAD article. The workflow integrates DecisionDx-SCC testing, which analyzes a patient’s tumor biology to independently predict risk of nodal or distant metastasis, and AJCC8 staging, which is based on a patient’s clinicopathologic risk factors, into current NCCN guidelines with a goal of improving precision in ART recommendations in the SCC patient population.

“As a panel, we agreed that the process used today to route SCC patients for ART can be improved, and DecisionDx-SCC can be a determining factor in the next step for management of high-risk SCC,” added Gaurav Singh, M.D., MPH, consensus panel member, and board-certified dermatologist, Mohs surgeon and assistant professor of dermatology in Wisconsin. “The test provides independent risk-stratification that can augment existing risk prediction systems, including AJCC8 and Brigham and Women’s Hospital (BWH) staging, to inform these important decisions with greater accuracy and ensure ART is brought to patients with the highest risk of disease progression who are most likely to benefit from treatment. DecisionDx-SCC can also help validate the decision to avoid radiation in seemingly high-risk tumors that are in fact low risk based on genetic profile.”

Specific consensus recommendations and statements outlined in the article include the following:

• A DecisionDx-SCC Class 2A or 2B result, indicating a higher or highest risk of metastasis, in each AJCC8 tumor stage serves as a high- or very high-risk feature for consideration in recommending ART.
  • The increased metastatic risk conferred by a Class 2A or 2B result in multivariate analysis (hazard ratio=2.3, p=0.013; and hazard ratio=6.9, p<0.001, respectively) is similar or higher than that conferred by other high-risk clinicopathologic features, including PNI and poor differentiation.
• Patients at the highest risk of metastasis, as indicated by a DecisionDx-SCC Class 2B test result, should be referred to radiation oncology with a recommendation for a multidisciplinary tumor board discussion.
• In nuanced discussions where the risks associated with ART may outweigh the benefits, the additional information provided by the DecisionDx-SCC test can assist in personalized decision-making.
• The DecisionDx-SCC test can help radiation oncologists determine a more precise risk-benefit ratio for elective nodal radiation.
  • The panel recommended stronger consideration of elective nodal radiation for a DecisionDx-SCC Class 2B tumor, given the dramatically increased risk of nodal metastasis.

Overall, the panel agreed the DecisionDx-SCC test provides independent risk stratification that, when combined with traditional staging and management guidelines, enhances the clinical picture, allowing clinicians to more accurately identify SCC patients who are most likely to benefit from ART, as well as lower-risk patients who would benefit less from treatment. In a validation study of the DecisionDx-SCC test by Wysong et al., metastatic risk prediction of AJCC8 and BWH staging systems was significantly improved when DecisionDx-SCC test results were included.³ As supported by the consensus article, the objective, independent risk stratification provided by the test can improve precision in multidisciplinary treatment recommendations, such as the use of ART, which could save the U.S. healthcare system hundreds of millions of dollars through more appropriate use of the treatment.⁴

About DecisionDx®-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), Class 2A (higher) or Class 2B (highest) risk category, predicts individual metastatic risk to inform risk-appropriate management. Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

About Castle Biosciences

Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. The Company aims to transform disease management by keeping people first: patients, clinicians, employees and investors.

Castle’s current portfolio consists of tests for skin cancers, Barrett’s esophagus, mental health conditions and uveal melanoma. Additionally, the Company has active research and development programs for tests in other diseases with high clinical need, including its test in development to help guide systemic therapy selection for patients with moderate-to-severe atopic dermatitis, psoriasis and related conditions. To learn more, please visit www.CastleBiosciences.com and connect with us on LinkedIn, Facebook, X and Instagram.

DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-SCC, MyPath Melanoma, DiffDx-Melanoma, TissueCypher, IDgenetix, 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 the DecisionDx-SCC test to (i) improve risk stratification and more accurately identify SCC patients at high risk of metastasis who may benefit from ART, (ii) provide independent risk stratification that, when combined with traditional staging and management guidelines, allows clinicians to more accurately identify SCC patients who are most likely to benefit from ART, as well as lower-risk patients who would benefit less from treatment and (iii) save our healthcare system hundreds of millions of dollars through more appropriate use of ART. The words “can,” “potential” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, 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 our actual results to differ materially from those in 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 recommendations and guidelines presented in this report, including with respect to the discussion of DecisionDx-Melanoma in this press release; actual application of our tests may not provide the aforementioned benefits to patients; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, and in our other filings with the SEC. 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 any forward-looking statements, except as may be required by law.

1. The authors of the consensus report and members of the multidisciplinary panel include the following physicians: Ramesh Gopal, M.D., Ph.D., a radiation oncologist and Associate Professor of Radiation Oncology at the New Mexico Comprehensive Cancer Center, in Albuquerque, New Mexico; Michael Marquardt, M.D., MPH, a radiation oncologist at Hall-Perrine Cancer Center, in Cedar Rapids, Iowa; Gaurav Singh, M.D., MPH, a board-certified dermatologist and Mohs surgeon in Wisconsin; Stanislav N. Tolkachjov, M.D., a board-certified dermatologist and Mohs micrographic and reconstructive surgeon at Epiphany Dermatology in Lewisville, Texas, Clinical Assistant Professor at the Department of Dermatology at University of Texas at Southwestern in Dallas, Texas, Clinical Associate Professor at the Texas A&M School of Medicine in Dallas, Texas, and a core faculty for the dermatology residency at Baylor University Medical Center in Dallas, Texas; Sarah T. Arron, M.D., Ph.D., a board-certified dermatologist and Mohs micrographic and reconstructive surgeon at Peninsula Dermatology Medical Group in Burlingame, California.
2. Gopal R, Marquardt M, Singh G, et al. Integrating 40-GEP Testing to Improve Clinical Recommendations for Adjuvant Radiation for Cutaneous Squamous Cell Carcinoma: Multidisciplinary Consensus Guidelines. J Clin Aesthet Dermatol. 2024;17(3 Suppl 2):S3–S8.
3. Wysong A, Newman JG, Covington KR, et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2021;84(2):361–369.
4. Somani SK, Ibrahim SF, Tassavor M, et al. Use of the 40-gene expression profile (40-gep) test in Medicare-eligible patients diagnosed with cutaneous squamous cell carcinoma (cSCC) to guide adjuvant radiation therapy (ART) decisions leads to a significant reduction in healthcare costs. J Clin Aesthet Dermatol. 2024;17(1):41–44.

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