Publication of Data from Prospective, Multicenter Study Demonstrates Positive Survival Outcomes in Patients with Low-Risk Melanoma Who Avoided Sentinel Lymph Node Biopsy with Information from Castle Biosciences’ DecisionDx®-Melanoma Test

Rhea-AI Summary

Castle Biosciences (CSTL) has published significant results from their DECIDE study regarding their DecisionDx-Melanoma test in melanoma patients. The study demonstrates the test's ability to accurately identify patients with less than 5% risk of sentinel lymph node (SLN) positivity who can safely avoid sentinel lymph node biopsy (SLNB) surgery.

Key findings show that DecisionDx-Melanoma influenced 85% of SLNB decisions. In patients with low-risk test results (Class 1A), none who underwent SLNB had positive nodes (0/35 patients). Notably, all patients with Class 1A results remained recurrence-free after two years of median follow-up, regardless of whether they underwent SLNB.

The study validates the test's alignment with National Comprehensive Cancer Network guidelines, which recommend avoiding SLNB when SLN positivity risk is below 5%. This helps reduce unnecessary surgical procedures, complications, and associated costs while focusing surgical interventions on higher-risk patients.

Positive

• 100% recurrence-free survival in low-risk patients after two years
• Test influenced 85% of SLNB surgical decisions
• Perfect accuracy in predicting low-risk cases (0/35 positive nodes)
• Potential reduction in unnecessary surgical procedures and associated costs

Negative

• None.

Insights

Medical Oncologist

The publication of Castle Biosciences' DECIDE study represents significant clinical validation for their DecisionDx-Melanoma test in melanoma management. The most compelling finding is that 100% of patients with a low-risk (Class 1A) result remained recurrence-free at median two-year follow-up, regardless of whether they underwent SLNB.

This data addresses a critical clinical need: identifying which T1-T2 melanoma patients can safely forgo SLNB. Current NCCN guidelines recommend avoiding SLNB when risk of nodal positivity is 5%, but clinical factors alone often cannot reliably identify these patients. The DecisionDx test provides molecular evidence to support this decision, with the study showing zero positive nodes among low-risk patients who still elected to undergo SLNB.

The test's ability to influence 85% of SLNB decisions demonstrates strong physician confidence in the molecular data. From a patient perspective, avoiding unnecessary surgery eliminates risks including lymphedema, infection, and nerve damage, while reducing healthcare costs and surgical resource utilization.

The multi-center, prospective study design strengthens the evidence quality beyond retrospective analyses. While longer follow-up would further validate durability of outcomes, these results strongly support incorporating DecisionDx-Melanoma testing into clinical practice for guiding SLNB decisions in patients with T1-T2 melanoma.

Healthcare Equity Analyst

Castle's DecisionDx-Melanoma test has demonstrated compelling clinical utility that should drive increased adoption and expand its addressable market. The test addresses a significant inefficiency in melanoma care - the fact that 88% of sentinel lymph node biopsies return negative results, suggesting substantial overtreatment.

By accurately identifying patients who can safely avoid SLNB (with 100% recurrence-free survival in the low-risk group), the test delivers value to multiple stakeholders: patients avoid unnecessary surgery, physicians make more confident decisions (influencing 85% of SLNB decisions), and payers benefit from reduced procedure costs.

The publication in multiple peer-reviewed journals strengthens Castle's position with clinicians and could accelerate reimbursement discussions with payers. The test's alignment with NCCN guidelines (which suggest forgoing SLNB when risk is 5%) provides a clear clinical adoption pathway.

For Castle specifically, this validation reinforces their precision medicine approach in dermatological cancers. The strength of these results suggests the test could become standard of care in T1-T2 melanoma management, representing a significant growth opportunity for the company as adoption increases. The data validates Castle's investment in the prospective DECIDE study and could strengthen market confidence in their diagnostic platform and development pipeline.

Consistent with prior studies, published results from Castle’s DECIDE study show DecisionDx-Melanoma can both accurately identify patients with less than 5% risk of sentinel lymph node (SLN) positivity, who can safely consider forgoing the sentinel lymph node biopsy (SLNB) surgical procedure, and who are also unlikely to experience disease progression^1,2

As of the last follow-up, all of the patients in the third study analysis with a low-risk DecisionDx-Melanoma test result (Class 1A) were recurrence free, regardless of SLN status³

FRIENDSWOOD, Texas, April 03, 2025 (GLOBE NEWSWIRE) -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced the recent publication of two papers in the World Journal of Surgical Oncology and Cancer Medicine sharing reports from the prospective, multicenter DECIDE study demonstrating the significant impact of the Company’s DecisionDx-Melanoma test on SLNB decision-making for patients with melanoma.^3,4

SLNB is a surgical procedure commonly used to determine whether a patient’s melanoma has spread to nearby lymph nodes. While useful in the prognosis of patients for whom cancer is found in the lymph nodes, SLNB returns a surgical result that is negative for metastasis in approximately 88% of patients who undergo the procedure.⁵ Current National Comprehensive Cancer Network^® (NCCN) guidelines suggest forgoing SLNB when the likelihood of finding a positive SLN is less than 5%, considering SLNB when the risk is between 5-10% and offering the surgery when the likelihood of positivity is above 10%. Castle’s prospective, multicenter DECIDE study was designed to assess the performance of the DecisionDx-Melanoma test in guiding SLNB decisions in patients with T1-T2 tumors and following these patients’ long-term outcomes.

“Decision-making for patients whose staging-based risk falls within or around the 5-10% threshold (i.e., patients with T1-T2 tumors) can be challenging. Our study findings underscore the strength of the DecisionDx-Melanoma test to accurately identify patients with T1-T2 tumors who have a low risk of metastasis and can safely forgo SLNB, within guideline recommendations, without experiencing a melanoma recurrence,” said J. Michael Guenther, M.D., lead study author and surgeon at St. Elizabeth Physicians in Edgewood, Kentucky. “As evidenced by the study data, use of the test’s results can significantly reduce unnecessary SLNB procedures while decreasing complication rates and reducing costs associated with the procedure. This test helps enable clinicians to focus surgical procedures on patients more likely to have a positive node.”

The initial report from DECIDE, published in 2023, showed that DecisionDx-Melanoma test results influenced 85% of SLNB decisions, demonstrating the significant clinical value of the test to help guide risk-aligned patient care.²

The second report, recently published in the World Journal of Surgical Oncology, confirmed the performance of a low-risk DecisionDx-Melanoma result to predict SLN positivity rates of less than 5% in patients who elected to have an SLNB despite the test result. In the second report, no patient with a DecisionDx-Melanoma-predicted risk of SLN positivity of less than 5% who decided to have an SLNB procedure had a positive node (0/35 patients).⁴

The third report, published in Cancer Medicine, shares outcomes of patients in the DECIDE study with a low-risk DecisionDx-Melanoma test result (Class 1A), of which approximately half (51.5%) decided to forgo an SLNB and 48.5% proceeded with an SLNB despite the DecisionDx-Melanoma test result. Of clinical significance, all patients with a low-risk Class 1A test result were recurrence free (100% recurrence free survival, median follow-up = two years).³

“DecisionDx-Melanoma helps empower patients and clinicians to make more informed, risk-aligned decisions about whether to safely forgo or pursue an SLNB based on the patient’s personal risk of SLN positivity,” continued Guenther. “Importantly, decisions to forgo the procedure can be made with confidence when guided by a low-risk DecisionDx-Melanoma test result.”

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 December 31, 2024, DecisionDx-Melanoma has been ordered approximately 191,800 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 to help guide systemic therapy selection for patients with moderate-to-severe atopic dermatitis seeking biologic 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: (i) the ability of the DecisionDx-Melanoma test to (a) 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, (b) significantly reduce unnecessary SLNB procedures while decreasing complication rates and reducing costs associated with the procedure and (c) enable clinicians to focus surgical procedures on patients more likely to have a positive node; and (ii) DecisionDx-Melanoma’s significant clinical value of the test to help guide risk-aligned patient care. 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. Yamamoto M, Sickle-Santanello B, Beard T, et al. The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study. Curr Med Res Opin. 2023;39(3):417-423. doi:10.1080/03007995.2023.2165813
2. Kriza C, Martin B, Bailey CN, Bennett J. Integrating the melanoma 31-gene expression profile test with clinical and pathologic features can provide personalized precision estimates for sentinel lymph node positivity: an independent performance cohort. World J Surg Oncol. 2024;22(1):228. doi:10.1186/s12957-024-03512-4
3. 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
4. Guenther JM, Ward A, Martin B, et al. A prospective, multicenter analysis of the integrated 31-gene expression profile test for sentinel lymph node biopsy (i31-GEP for SLNB) test demonstrates reduced number of unnecessary SLNBs in patients with cutaneous melanoma. World J Surg Oncol. 2025 Jan 3;23(1):5. doi: 10.1186/s12957-024-03640-x
5. Chen J, Xu Y, Wang Y, et al. Prognostic role of sentinel lymph node biopsy for patients with cutaneous melanoma: A retrospective study of surveillance, epidemiology, and end-result population-based data. Oncotarget. 2016;7(29):45671-45677. doi:10.18632/oncotarget.10140
   

Investor Contact:
Camilla Zuckero
czuckero@castlebiosciences.com

Media Contact:
Allison Marshall
amarshall@castlebiosciences.com

Source: Castle Biosciences Inc.

FAQ

What are the success rates of Castle Biosciences' DecisionDx-Melanoma test in the DECIDE study?

The study showed 100% recurrence-free survival for patients with low-risk (Class 1A) results after two years median follow-up, and 0% positive nodes in patients who underwent SLNB despite low-risk results.

How does DecisionDx-Melanoma impact SLNB decision-making for CSTL?

The test influenced 85% of SLNB decisions, helping identify patients with <5% risk of SLN positivity who can safely avoid the surgical procedure.

What percentage of patients with low-risk DecisionDx-Melanoma results chose to skip SLNB?

51.5% of patients with low-risk (Class 1A) results chose to forgo SLNB, while 48.5% proceeded with the procedure despite the test results.

How does Castle Biosciences' melanoma test align with NCCN guidelines?

The test aligns with NCCN guidelines by identifying patients with <5% risk of SLN positivity who can safely forgo SLNB, supporting guideline recommendations for surgical decisions.