DecisionDx®-Melanoma's i31-SLNB Outperforms MIA Nomogram in Identifying Patients Who May Safely Forgo Sentinel Lymph Node Biopsy

Newly published prospective study shows DecisionDx-Melanoma's i31-SLNB test result more accurately identifies patients at low and high risk of sentinel lymph node (SLN) positivity than the Melanoma Institute Australia (MIA) nomogram

Patients classified as low risk by the i31-SLNB result had a 2.6% observed SLN positivity rate, falling well below the National Comprehensive Cancer Network (NCCN) 5% threshold used to consider avoiding sentinel lymph node biopsy (SLNB), compared with a 5.8% observed positivity rate for the MIA nomogram

FRIENDSWOOD, Texas, June 25, 2026 /PRNewswire/ -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of a prospective, multicenter study in Dermatology and Therapy demonstrating that DecisionDx-Melanoma's integrated sentinel lymph node biopsy test result (i31-SLNB) outperforms the MIA nomogram in identifying patients at low and high risk of SLN positivity, supporting more informed SLNB decision-making for patients with cutaneous melanoma (CM). 1 This is the second multicenter study showing that the i31-SLNB result outperforms the MIA nomogram in assessing SLN positivity risk. 2

"Many clinicians are familiar with nomograms that estimate risk of sentinel lymph node positivity using clinicopathologic features alone, yet current guidelines acknowledge limitations in their performance at lower risk thresholds," said Rohit Sharma, M.D., FACS, lead author of the study and surgical oncologist at Marshfield Clinic Health System in Marshfield, Wisconsin. "Because of this, accurately identifying which patients are unlikely to have sentinel lymph node involvement remains an important challenge in melanoma care. The study findings demonstrate that incorporating tumor biology through DecisionDx-Melanoma's i31-SLNB test result can improve risk assessment, helping clinicians better distinguish which patients with melanoma may safely avoid SLNB and which should consider having the surgery."

Key findings from the study include:

SLNB plays an important role in melanoma staging by helping determine whether melanoma has spread to nearby lymph nodes. However, up to 88% of SLNB procedures are negative and approximately 15% of patients experience surgery-associated complications. Current NCCN CM Guidelines recommend avoiding SLNB when the likelihood of SLN positivity is less than 5%, considering the procedure when risk is between 5% and 10%, and offering SLNB when risk exceeds 10%. These thresholds create a need for tools that can more accurately identify patients who may safely avoid the procedure while appropriately identifying those at higher risk.

The study, titled "Comparing the i31-SLNB and the MIA Nomogram for Sentinel Lymph Node Biopsy Positivity Prediction in Cutaneous Melanoma: A Prospective Cohort Analysis," evaluated 912 patients considering SLNB enrolled in the multicenter DECIDE study and directly compared the performance of DecisionDx-Melanoma's i31-SLNB result, which integrates the 31-gene expression profile (31-GEP) score with clinicopathologic factors, with the MIA nomogram, which estimates SLN positivity risk using clinicopathologic factors alone.

The study found that patients undergoing SLNB classified as low risk by the i31-SLNB (less than 5% predicted risk of SLN positivity) had an observed SLN positivity rate of 2.6%, showing concordance with predicted results. Patients predicted to have less than 5% risk of SLN positivity by the MIA nomogram had an observed positivity rate of 5.8%, showing discordance with predicted results; the MIA nomogram failed to identify patients below the 5% NCCN threshold used to consider avoiding SLNB.

The study also examined patients whose risk predictions were discordant between the two approaches. Among patients classified as low risk (less than 5%) by the i31-SLNB but higher risk (greater than or equal to 5%) by the MIA nomogram, the observed SLN positivity rate was only 2.8%. Conversely, among patients classified as low risk by the MIA nomogram but higher risk by the i31-SLNB, the observed positivity rate was 11.5%, demonstrating that the i31-SLNB again outperformed the MIA nomogram.

Overall, the i31-SLNB result demonstrated greater discriminative performance than the clinicopathologic-only MIA nomogram (AUC=0.74 vs. 0.61; p=0.001), indicating improved accuracy in identifying patients at both low and high risk of SLN positivity.

These findings are consistent with previously published evidence, including Zakria et al, 2022, a retrospective, multicenter study that also showed DecisionDx-Melanoma outperformed the MIA nomogram. 2 They also add to the growing body of prospective evidence supporting the use of DecisionDx-Melanoma to inform SLNB decision-making and further demonstrate the value of integrating tumor biology with clinicopathologic factors to improve risk assessment and support more informed, risk-aligned care for patients with CM. 3-6

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile (GEP) test designed to analyze tumor biology to deliver a personalized risk assessment for patients with stage I–III cutaneous melanoma, enhancing risk stratification beyond American Joint Committee on Cancer (AJCC) staging alone. By combining molecular insights with select clinicopathologic features, the test provides two distinct outputs: a personalized risk of sentinel lymph node (SLN) positivity and a personalized risk of recurrence and/or metastasis. This clinically actionable information is designed to help guide risk-aligned patient management decisions, including SLN biopsy consideration, follow-up intensity, imaging and referrals.

DecisionDx-Melanoma is supported by more than 50 peer-reviewed publications, including prospective studies and meta-analyses, and was developed in collaboration with more than 100 leading U.S. institutions. The test has been clinically validated in more than 10,000 patient samples, ordered more than 240,000 times since launch, and has been shown to be associated with improved patient survival. 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. 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-Melanoma's i31-SLNB test to (i) accurately identify patients at low and high risk of SLN positivity and support more informed SLNB decision-making for patients with cutaneous melanoma; (ii) help clinicians distinguish which patients with melanoma may safely avoid SLNB and which are more likely to benefit from the procedure; (iii) generate a personalized likelihood of SLN positivity to support risk-aligned shared decision-making consistent with NCCN guideline thresholds; and (iv) improve risk assessment and support more informed, risk-aligned care for patients with CM. The words "designed," "may," "can," "supporting," "helping," "intended to" and similar expressions are intended to identify forward 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 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 certain 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, 2025, and our subsequent Quarterly Reports on Form 10-Q, each as filed or to be filed with the SEC, 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.

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SOURCE Castle Biosciences, Inc.