New Study Shows Castle Biosciences’ DecisionDx®-Melanoma Test Outperforms Staging and CP-GEP in Identifying Patients at Low Risk of Sentinel Lymph Node Positivity

Rhea-AI Summary

Castle Biosciences (Nasdaq: CSTL) has published a new study showing their DecisionDx-Melanoma test surpasses both AJCC staging and CP-GEP in identifying low-risk melanoma patients. The test achieved a 2.8% sentinel lymph node positivity rate, significantly below the NCCN guidelines' 5% threshold for avoiding sentinel lymph node biopsy (SLNB) surgery.

The study, published in Cancer Diagnosis & Prognosis, analyzed T1-T2 melanoma tumors across multiple validation studies. While patients classified as low risk by CP-GEP showed a 6.2% SLN positivity rate, DecisionDx-Melanoma demonstrated superior performance at 2.8%. This improvement is particularly significant as over 90% of T1-T2 tumor patients who undergo SLNB receive negative results.

The findings support using DecisionDx-Melanoma to guide SLNB decisions, especially for patients with thin tumors where surgical complications may outweigh benefits. The test provides personalized risk assessment for sentinel lymph node positivity and recurrence, enabling more informed melanoma management decisions.

Positive

• DecisionDx-Melanoma test shows superior performance with only 2.8% false positive rate vs competitor's 6.2%
• Test outperforms both current standard AJCC staging and competing CP-GEP test in identifying low-risk patients
• Strong validation through multiple prospective and retrospective studies
• Product helps reduce unnecessary surgeries, potentially increasing adoption and market share
• Test results show high accuracy in identifying low-risk patients, strengthening product's clinical value proposition

Negative

• None.

Insights

Medical Diagnostics Expert

Castle's DecisionDx-Melanoma test shows superior performance in identifying low-risk melanoma patients who can safely avoid unnecessary surgical procedures.

The newly published study in Cancer Diagnosis & Prognosis provides compelling evidence that Castle Biosciences' DecisionDx-Melanoma test significantly outperforms both traditional AJCC staging and the competing CP-GEP genomic test in identifying patients at low risk for sentinel lymph node (SLN) positivity.

The most clinically significant finding is that patients classified as low risk by DecisionDx-Melanoma demonstrated only a 2.8% SLN positivity rate, substantially below the 5% threshold established by NCCN guidelines for safely forgoing sentinel lymph node biopsy (SLNB). In striking contrast, the competing CP-GEP test identified patients as "low risk" who actually had a 6.2% SLN positivity rate - exceeding the safety threshold.

This distinction has substantial clinical implications. SLNB is a surgical procedure with potential complications, and the ability to confidently identify truly low-risk patients means fewer unnecessary surgeries. This is particularly relevant for T1-T2 melanoma patients, who constitute the majority of newly diagnosed cases, where over 90% of these patients currently receive negative SLNB results.

The test's validation across multiple prospective and retrospective studies provides robust evidence supporting its performance. The data reinforces DecisionDx-Melanoma as a valuable clinical decision support tool that can help clinicians and patients make more informed, risk-aligned melanoma management decisions - potentially improving both clinical outcomes and healthcare resource utilization.

Financial Analyst

Castle Biosciences strengthens competitive position with clinical data showing DecisionDx-Melanoma outperforms both standard staging and competing genomic tests.

The publication of this comparative study represents a significant competitive advantage for Castle Biosciences in the precision oncology diagnostics market. By demonstrating that DecisionDx-Melanoma identifies patients with less than a 5% risk of SLN positivity with greater accuracy than both traditional staging methods and a competing genomic test, the company reinforces its product's clinical utility and differentiation.

This performance differentiation is particularly valuable in the substantial melanoma diagnostics market. With approximately 100,000 invasive melanoma cases diagnosed annually in the US, and the majority being T1-T2 tumors, the potential addressable market for this test is considerable. The data showing superior risk stratification supports the test's value proposition to clinicians, patients, and payers alike.

The study aligns with healthcare's focus on reducing unnecessary procedures. Given that over 90% of patients with T1-T2 tumors who undergo SLNB receive negative results, a test that accurately identifies low-risk patients can help reduce surgical procedures and their associated costs and complications. This value proposition resonates with current healthcare priorities of improving patient outcomes while optimizing resource utilization.

This publication builds upon Castle Biosciences' existing clinical validation portfolio, with DecisionDx-Melanoma having been validated in multiple prospective and retrospective studies. The continued strengthening of the clinical evidence supporting the test reinforces its potential role as a standard component of melanoma management, potentially driving increased clinical adoption.

Patients identified as low risk by DecisionDx-Melanoma had a 2.8% sentinel lymph node (SLN) positivity rate, well below the National Comprehensive Cancer Network® (NCCN) guidelines’ 5% threshold to forgo sentinel lymph node biopsy (SLNB) surgery

FRIENDSWOOD, Texas, April 30, 2025 (GLOBE NEWSWIRE) -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of a new study in Cancer Diagnosis & Prognosis demonstrating that DecisionDx-Melanoma outperforms both American Joint Committee on Cancer (AJCC) staging and the CP-GEP test (clinicopathological and gene expression profiling model) in identifying patients at low risk of SLN positivity who may consider forgoing SLNB surgery.¹

“When relying on genomic testing to guide critical decisions about procedures like SLNB, a test must demonstrate exceptional accuracy in identifying patients with minimal risk of metastasis," said Peter A. Prieto, M.D., MPH, lead author and triple board-certified surgical oncologist at the University of Rochester Medical Center. "Our study confirms that DecisionDx-Melanoma achieves this by providing significant risk stratification, outperforming the standard of care (i.e., AJCC staging) and the CP-GEP genomic test.”

SLNB helps determine whether melanoma has spread to nearby lymph nodes. Current NCCN guidelines recommend forgoing SLNB if the risk of a positive node is below 5%, considering it at 5-10% and offering if a patient’s risk exceeds 10%. The majority of newly diagnosed melanomas are T1–T2 tumors, yet more than 90% of patients who undergo SLNB in this population receive negative results.²^,³ Further, in patients with thin tumors, the risk of procedural complications outweighs the likelihood of a positive node, underscoring the need for better tools to identify low-risk patients who can safely avoid the surgery.⁴

DecisionDx-Melanoma has been validated in multiple prospective and retrospective studies to provide significant risk stratification independent of clinicopathological features such as age and Breslow thickness.^5-8 The test provides personalized results on a patient’s likelihood of sentinel lymph node positivity and risk of recurrence, helping clinicians and patients make more informed, risk-aligned melanoma management decisions.

The new study provides an analysis of the accuracy of the CP-GEP and DecisionDx-Melanoma tests in identifying patients with less than a 5% risk of SLN positivity, in T1-T2 tumors specifically, across five CP-GEP and four DecisionDx-Melanoma validation studies. Using a weighted average across all studies, patients classified as low risk by CP-GEP had an SLN positivity rate of 6.2%, exceeding the 5% NCCN threshold for ruling out SLNB. In contrast, patients identified as low risk by DecisionDx-Melanoma had a 2.8% SLN positivity rate, a significant improvement over AJCC staging. Overall, CP-GEP did not perform as well as staging alone, while DecisionDx-Melanoma outperformed staging, providing further confirmation of its ability to improve clinical decision-making and ultimately, outcomes.

“This study underscores the value of using DecisionDx-Melanoma test results to help guide improved SLNB decisions,” said Matthew Goldberg, M.D., senior vice president, medical, of Castle Biosciences. “Further, it strengthens our recent prospective study findings, which show that patients with low-risk DecisionDx-Melanoma results (less than 5% likelihood of SLN positivity) who forgo SLNB surgery maintain high recurrence-free survival rates, providing clinicians and patients with greater confidence in treatment decisions guided by our test.”⁹

About DecisionDx^®-Melanoma
DecisionDx-Melanoma is a gene expression profile risk stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient’s individual risk of sentinel lymph node positivity and a patient's personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma’s clinical value is supported by more than 50 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through March 31, 2025, DecisionDx-Melanoma has been ordered more than 200,000 times for patients diagnosed with cutaneous melanoma. Learn more at www.CastleBiosciences.com.

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 these and other diseases with high clinical need, including its test in development for use in patients diagnosed with moderate-to-severe atopic dermatitis who are seeking systemic treatment. To learn more, please visit www.CastleBiosciences.com and connect with us on LinkedIn, Facebook, X and Instagram. 

DecisionDx-Melanoma, DecisionDx-CMSeq, i31-SLNB, i31-ROR, 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-Melanoma test to (i) provide significant risk stratification and outperform the standard of care and the CP-GEP genomic test, (ii) accurately identify patients with less than 5% risk of SLN positivity, who can safely consider forgoing the SLNB surgical procedure, and who are also unlikely to experience disease progression, (iii) enhance clinical decision-making and (iv) deliver risk-aligned patient care and provide clinicians and patients with greater confidence in treatment decisions. The words “believe,” “can,” “could,” “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 results obtained in these studies, including with respect to the discussion of our tests 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, 2024 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. Prieto PA, Ferris LK, Guenther MJ. Comparing Two Gene Expression Profile Tests to Standard of Care for Identifying Patients With Cutaneous Melanoma at Low Risk of Sentinel Lymph Node Positivity. Cancer Diagn Progn. 2025;5(3):261-267. doi: 10.21873/cdp.10438
2. Chen ML, de Vere Hunt IJ, John EM, Weinstock MA, Swetter SM, Linos E. Differences in Thickness-Specific Incidence and Factors Associated With Cutaneous Melanoma in the US From 2010 to 2018 [published correction appears in JAMA Oncol. 2022 Oct 1;8(10):1518. doi: 10.1001/jamaoncol.2022.4054.]. JAMA Oncol. 2022;8(5):755-759. doi:10.1001/jamaoncol.2022.0134
3. Le ELH, Lamping E, Helmkamp L, et al. Analysis of Time Between Skin Lesion and Lymph Node Biopsies and Lymph Node Metastasis in Patients With Melanoma. JAMA Netw Open. 2023;6(5):e2311472. Published 2023 May 1. doi:10.1001/jamanetworkopen.2023.11472
4. Moody JA, Ali RF, Carbone AC, Singh S, Hardwicke JT. Complications of sentinel lymph node biopsy for melanoma - A systematic review of the literature. Eur J Surg Oncol. 2017;43(2):270-277. doi:10.1016/j.ejso.2016.06.407
5. Bailey CN, Martin BJ, Petkov VI, et al. 31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration. JCO Precis. Oncol. 2023; 7. doi: 10.1200/PO.23.00044
6. Hsueh EC, DeBloom JR, Lee JH, et al. Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma. JCO Precis. Oncol. 2021; 5. doi: 10.1200/PO.20.00119
7. Gerami P, Cook RW, Wilkinson J, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. 2015;21(1):175-183. doi:10.1158/1078-0432.CCR-13-3316
8. Gerami P, Cook RW, Russell MC, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. 2015;72(5):780-5.e3. doi:10.1016/j.jaad.2015.01.009
9. Guenther JM, Ward A, Martin BJ, et al. A Prospective, Multicenter Analysis of Recurrence-Free Survival After Sentinel Lymph Node Biopsy Decisions Influenced by the 31-GEP. Cancer Med. 2025;14(7):e70839. doi:10.1002/cam4.70839
   

Investor Contact:
Camilla Zuckero
czuckero@castlebiosciences.com

Media Contact:
Allison Marshall
amarshall@castlebiosciences.com

Source: Castle Biosciences Inc.

FAQ

How accurate is Castle Biosciences' DecisionDx-Melanoma test for sentinel lymph node positivity?

According to the 2025 study, DecisionDx-Melanoma shows a 2.8% sentinel lymph node positivity rate in low-risk patients, performing better than both AJCC staging and CP-GEP test, and well below the NCCN's 5% threshold for avoiding SLNB surgery.

What are the benefits of Castle Biosciences (CSTL) DecisionDx-Melanoma test over traditional staging?

DecisionDx-Melanoma outperforms traditional AJCC staging by providing personalized risk assessment for sentinel lymph node positivity and recurrence risk, helping patients potentially avoid unnecessary SLNB surgery when identified as low-risk.

How does CSTL's DecisionDx-Melanoma compare to CP-GEP test for melanoma patients?

DecisionDx-Melanoma (2.8% positivity rate) significantly outperforms CP-GEP (6.2% positivity rate) in identifying low-risk melanoma patients, with CP-GEP performing worse than standard staging alone.

What percentage of T1-T2 melanoma patients could avoid SLNB surgery with DecisionDx-Melanoma?

While over 90% of T1-T2 melanoma patients currently receive negative SLNB results, DecisionDx-Melanoma can identify patients with less than 5% risk, helping them safely avoid unnecessary surgery.

What is the clinical impact of Castle Biosciences' 2025 melanoma test study?

The study validates DecisionDx-Melanoma's ability to accurately identify low-risk patients who can safely avoid SLNB surgery, potentially reducing unnecessary procedures while maintaining high recurrence-free survival rates.