Prospective, Multi-center Study Published in Future Oncology Demonstrates DecisionDx®-Melanoma’s i31-SLNB Result Outperforms Staging Criteria in Identifying Patients with Cutaneous Melanoma Below the 5% NCCN Threshold for Forgoing SLNB

Rhea-AI Summary

Castle Biosciences (Nasdaq: CSTL) published a prospective multicenter study in Future Oncology showing DecisionDx-Melanoma’s i31-SLNB identifies patients below the NCCN 5% threshold for forgoing SLNB. Key results: 2.6% observed SLN positivity overall for 5% predicted patients; in T1b–T2a; 97.8% three-year RFS in low-risk patients. The i31-SLNB produced TN:FN ratios of 55:1 (T1–T2a) and 73:1 (T1b–T2a), exceeding the 19:1 guideline benchmark. A webcast will be held March 23, 2026, to discuss the data.

Positive

• Observed 2.6% SLN positivity for patients predicted <5% risk
• Observed 1.4% SLN positivity in T1b–T2a patients predicted <5% risk
• 97.8% three‑year recurrence‑free survival for low‑risk patients
• TN:FN ratio 73:1 in T1b–T2a, exceeding 19:1 benchmark
• TN:FN ratio 55:1 in T1–T2a, exceeding guideline benchmark

Negative

• Only 430 of 912 enrolled patients underwent sentinel lymph node biopsy
• 482 of 912 patients did not receive SLNB, limiting nodal-confirmation sample size

News Market Reaction – CSTL

+0.95%

1 alert

+0.95% News Effect

On the day this news was published, CSTL gained 0.95%, reflecting a mild positive market reaction.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Nodal positivity (low-risk): 2.6% Three-year RFS: 97.8% High-risk SLN positivity: 21.4% +5 more

8 metrics

Nodal positivity (low-risk) 2.6% Patients predicted <5% SLN risk by i31-SLNB

Three-year RFS 97.8% Low-risk i31-SLNB patients with ≥2 years follow-up

High-risk SLN positivity 21.4% Patients with >10% predicted SLN risk by i31-SLNB

Study enrollment 912 patients Prospective multicenter cutaneous melanoma study

SLNB performed 430 patients Patients undergoing sentinel lymph node biopsy

TN:FN ratio T1–T2a 55:1 i31-SLNB performance vs 19:1 NCCN benchmark

TN:FN T1b–T2a 73:1 i31-SLNB clinically important early-stage subgroup

CP-GEP TN:FN 15:1 Previously reported CP-GEP in T1–T2 disease

Market Reality Check

Price: $25.90 Vol: Volume 387,604 vs 20-day ...

normal vol

$25.90 Last Close

Volume Volume 387,604 vs 20-day average 454,451 (relative volume 0.85) suggests no outsized trading reaction pre-news. normal

Technical Shares at $25.32 are trading below the 200-day MA of $27.34, and remain 42.82% under the 52-week high.

Peers on Argus

CSTL was down 3.1% while only one peer (PSNL) appeared in momentum scans, moving...

1 Up

CSTL was down 3.1% while only one peer (PSNL) appeared in momentum scans, moving up, and other key peers showed mixed moves. This points to stock-specific dynamics rather than a coordinated sector move.

Historical Context

5 past events · Latest: Mar 09 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Mar 09	Clinical study data	Positive	-0.4%	Prospective multicenter study confirming i31-SLNB accurately predicts low SLN risk.
Mar 04	Conference presentation	Positive	-0.9%	Upcoming SSO 2026 data on i31-SLNB helping identify T1b–T2a patients avoiding SLNB.
Mar 03	HQ expansion	Positive	+2.2%	Announcement of new Friendswood headquarters supporting growth and operations.
Feb 26	Earnings results	Positive	-7.3%	Full-year 2025 revenue of <b>$344.2M</b> exceeding guidance with strong test volume growth.
Feb 19	Clinical validation	Positive	-6.8%	AdvanceAD-Tx™ study showing JAK responder profile linked to deeper, faster responses.

Pattern Detected

Recent history shows frequent sell-offs on otherwise positive operational, clinical, and earnings updates, indicating a pattern of divergence between news tone and short-term price reaction.

Recent Company History

Over the last month, Castle Biosciences has reported several positive developments: prospective multicenter data validating DecisionDx-Melanoma’s i31-SLNB (Mar 9), new data presentations at SSO 2026 (Mar 4), a new Friendswood headquarters opening (Mar 24, 2026 event), strong $344.2M 2025 revenue beating guidance, and favorable AdvanceAD-Tx™ validation results. Yet, four of these five items saw negative next-day reactions, suggesting investors often fade good news and may be sensitive to valuation or profit-taking.

Market Pulse Summary

This announcement presents robust prospective, multicenter evidence that DecisionDx-Melanoma’s i31-S...

Analysis

This announcement presents robust prospective, multicenter evidence that DecisionDx-Melanoma’s i31-SLNB refines sentinel lymph node biopsy decisions in cutaneous melanoma. Low-risk patients showed only 2.6% nodal positivity and 97.8% three-year recurrence-free survival, with TN:FN ratios up to 73:1 in key early-stage subgroups. In context of Castle’s recent stream of positive clinical and operational news, investors may focus on how broader guideline adoption, utilization trends, and future data updates influence the long-term impact of this test.

Key Terms

sentinel lymph node biopsy, slnb, gene expression profile, breslow thickness, +4 more

8 terms

sentinel lymph node biopsy medical

"threshold for forgoing sentinel lymph node biopsy (SLNB) and outperforms"

A sentinel lymph node biopsy is a surgical procedure that removes and tests the first lymph node(s) that drain fluid from a tumor to see if cancer has spread. Think of it as checking the first security checkpoint after a breach; a negative result often means less extensive surgery and lower treatment costs, while a positive result can change therapy, prognosis, regulatory decisions and market demand for related diagnostics and treatments, making it important to investors.

slnb medical

"threshold for forgoing SLNB when the likelihood of SLN positivity is less than 5%"

A sentinel lymph node biopsy is a surgical test that removes and examines the first lymph node(s) likely to receive cancer cells from a tumor, like checking the first bucket under a leaking pipe to see whether the problem has spread. Investors care because SLNB results shape treatment decisions, clinical trial endpoints and regulatory outcomes for cancer drugs and devices, so those findings can materially affect a company’s clinical prospects and market value.

gene expression profile medical

"other predictive gene expression profile (GEP) tests, (i.e., CP-GEP)"

A gene expression profile is a snapshot of which genes in a cell or tissue are switched on and how strongly they are producing their products, like a theater marquee showing which plays are running and how popular each is. For investors, these profiles matter because they can indicate whether a drug or diagnostic is likely to work, reveal which patient groups will benefit, and reduce development time and risk—factors that influence a biotech company’s value and commercial prospects.

breslow thickness medical

"factors, including Breslow thickness, ulceration, mitotic rate and age,"

Breslow thickness is a pathologist’s measurement of how deep a melanoma tumor has grown into the skin, reported in millimeters. It matters to investors because deeper tumors predict worse outcomes, influence treatment choices, determine clinical trial eligibility and regulatory decisions, and therefore can affect demand for therapies, diagnostic tools and reimbursement — like measuring the depth of a crack to judge how costly a repair will be.

mitotic rate medical

"including Breslow thickness, ulceration, mitotic rate and age, to generate"

Mitotic rate is a measure of how quickly cells in a tissue sample are dividing, reported by a pathologist after counting dividing cells under a microscope. For investors, it signals how aggressive a tumor or disease may be—like measuring how fast weeds are spreading in a garden—and can influence prognosis, treatment choices, clinical trial outcomes and the commercial value of therapies or diagnostic tests.

recurrence-free survival medical

"2.6% nodal positivity and 97.8% three-year recurrence-free survival (RFS)"

Recurrence-free survival is the length of time after a treatment during which a patient shows no return of disease. It’s used in clinical trials to measure how well a therapy prevents the illness from coming back — think of it like the time a repaired roof stays leak-free. For investors, longer recurrence-free survival suggests a treatment is more effective, which can improve chances of regulatory approval, commercial uptake, and long-term revenue.

true-negative technical

"reports true-negative to false-negative (TN:FN) ratios comparing the standard"

A true-negative is a correct result from a medical or diagnostic test that indicates a condition is absent when it really is absent. For investors, high rates of true-negatives mean a test or product reliably avoids false alarms, which reduces unnecessary costs, improves regulatory and market confidence, and signals that a diagnostic tool or screening program is behaving as advertised—like a smoke detector that stays silent when there’s no fire.

false-negative technical

"reports true-negative to false-negative (TN:FN) ratios comparing the standard"

A false-negative occurs when a test or analysis reports that a condition is absent when it is actually present — like a smoke detector that fails to sound during a fire. In finance and regulation, false-negatives can mean clinical trials, safety screens, or market analyses miss a real effect or risk; for investors that can lead to undervaluing an asset, missed investment opportunities, or unexpected regulatory surprises that move a company’s stock.

AI-generated analysis. Not financial advice.

Among all patients studied, 2.6% nodal positivity and 97.8% three-year recurrence-free survival (RFS) was observed in those predicted to have less than 5% risk of a positive sentinel lymph node (SLN) by DecisionDx-Melanoma’s i31-SLNB

Only 1.4% SLN positivity was observed in patients with T1b–T2a tumors predicted to have less than 5% risk

The Company will host a webcast on Monday, March 23, at 4:30pm Eastern Time to discuss data from the publication

FRIENDSWOOD, Texas, March 13, 2026 (GLOBE NEWSWIRE) -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of results from the largest prospective, multicenter study to date evaluating DecisionDx-Melanoma’s integrated sentinel lymph node biopsy (i31-SLNB) test result.¹ The paper, available in Future Oncology, confirms that DecisionDx-Melanoma’s i31-SLNB identifies patients below the 5% National Comprehensive Cancer Network^® (NCCN) threshold for forgoing sentinel lymph node biopsy (SLNB) and outperforms traditional staging criteria and other predictive gene expression profile (GEP) tests.

“What makes these findings meaningful is the clear separation between low- and high-risk patients using DecisionDx-Melanoma’s i31-SLNB,” said J. Michael Guenther, M.D., co-author and surgical oncologist at St. Elizabeth Physicians in Edgewood, Kentucky. “When a patient’s predicted risk is below 5%, the observed precision of the i31-SLNB gives us great confidence that forgoing SLNB is appropriate, while still maintaining excellent outcomes for our patients. Conversely, patients predicted to have a greater than 10% likelihood of a positive SLN by the i31-SLNB had an actual SLN positivity rate of 21.4% — more than eight times higher than those predicted to have a low likelihood of a positive SLN.”

Current NCCN Cutaneous Melanoma (CM) Guidelines recommend forgoing SLNB when the likelihood of SLN positivity is less than 5%, considering SLNB when risk is between 5–10% and offering the procedure when risk exceeds 10%. DecisionDx-Melanoma’s i31-SLNB integrates the independently validated 31-GEP score with established clinicopathologic factors, including Breslow thickness, ulceration, mitotic rate and age, to generate a personalized likelihood of SLN positivity that supports decision-making aligned with these guideline thresholds.

In this prospective, multicenter study of 912 patients with T1–T4 cutaneous melanoma enrolled across 30 U.S. centers, 430 patients underwent SLNB and 482 did not, allowing for evaluation of both nodal positivity and recurrence outcomes.

Among patients who underwent SLNB:

• Patients with less than 5% predicted risk of SLN positivity by DecisionDx-Melanoma’s i31-SLNB had an actual SLN positivity rate of 2.6%.
• Patients with greater than 10% predicted risk had an SLN positivity rate of 21.4%, an 8.2-fold greater likelihood.
  
  

In early-stage disease where SLNB decision-making is often most nuanced:

• Among patients with T1–T2a tumors, SLN positivity was only 1.8% in those with an i31-SLNB less than 5% predicted risk.
• In contrast, SLN positivity was 16.7% in those with greater than 10% predicted risk by i31-SLNB, a 9.3-fold greater likelihood.
  
  

All patients with a low-risk i31-SLNB result (less than predicted 5% risk) who had at least two years of follow up (or a recurrence) demonstrated a 97.8% three-year RFS rate, indicating a very low risk of recurrence.

Beyond nodal positivity rates, the study also evaluated performance relative to established guideline benchmarks and other predictive tests. Table 3 from the manuscript (available here) reports true-negative to false-negative (TN:FN) ratios comparing the standard established by NCCN guidelines which uses American Joint Committee on Cancer (AJCC) staging criteria, DecisionDx-Melanoma’s i31-SLNB and other predictive gene expression profile tests, (i.e., CP-GEP), across tumor stages.

A TN:FN ratio of 19:1 corresponds to a 5% miss rate, meaning that for every 19 true-negative SLNBs, one positive SLNB would have been missed, consistent with NCCN guideline thresholds. Ratios greater than 19:1 indicate performance exceeding AJCC/NCCN guidance, while ratios below 19:1 indicate higher miss rates.

In this study, the i31-SLNB demonstrated a TN:FN ratio of 55:1 in T1–T2a patients and 73:1 in the clinically important T1b–T2a subgroup, exceeding the 19:1 guideline benchmark. By comparison, previously reported data for other predictive GEP tests, including CP-GEP in T1–T2 disease, have shown lower TN:FN ratios (15:1). These findings highlight the ability of the i31-SLNB to more precisely identify patients at low risk of SLN positivity while minimizing missed positive nodes, particularly in early-stage tumors where accurate identification below the 5% threshold is critical to avoid unnecessary procedures.

Overall, the published data confirm that DecisionDx-Melanoma’s i31-SLNB can identify patients at sufficiently low risk of nodal positivity to safely forgo SLNB, reducing unnecessary procedures, procedure-related complications and healthcare costs while supporting risk-aligned management.

Webcast Details
The live webcast will take place on March 23, 2026, at 4:30 p.m. Eastern Time and can be accessed here: https://events.q4inc.com/attendee/394408771, or via the webcast link on the Investor Relations page of the Company’s website: https://ir.castlebiosciences.com/overview/default.aspx. A replay of the webcast will be available following its conclusion.

Speaker details:
J. Michael Guenther, M.D., surgical oncologist, St. Elizabeth Physicians, Edgewood, Kentucky

• John Wayne Institute – Fellowship (Santa Monica, CA)
• University of Cincinnati – Residency (Cincinnati, OH)
• University of Michigan Medical School (Ann Arbor, MI)
• American Board of Surgery: General
  
  

There will be a brief Question and Answer session following prepared remarks.

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 220,000 times since launch, and has been shown to be associated with improved patient survival. Learn more at https://castlebiosciences.com/tests/prognostic/decisiondx-melanoma/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, 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) generate a personalized likelihood of SLN positivity to support risk-aligned shared decision-making consistent with NCCN guideline thresholds; and (ii) reduce unnecessary procedures, procedure-related complications and healthcare costs. The words “designed,” “may”, “can”, 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.

1. Beard T, Guenther JM, Leong SP, et al. The integrated 31-gene expression profile test identifies low-risk patients with cutaneous melanoma who can forego the SLNB procedure: results from a prospective, multicenter trial. Future Oncol. Published online [March 13, 2026]. doi: https://doi.org/10.1080/14796694.2026.2640227

Investor and Media Contact:
Camilla Zuckero
281-906-3868
czuckero@castlebiosciences.com

Source: Castle Biosciences, Inc.

FAQ

What were the key DecisionDx-Melanoma i31-SLNB results published March 13, 2026 for CSTL?

The study reported 2.6% observed SLN positivity for patients predicted <5% risk and 97.8% three-year RFS for low-risk patients. According to the company, results came from a 912-patient prospective, multicenter cohort across 30 U.S. centers.

How did i31-SLNB perform in early-stage T1b–T2a melanomas in the CSTL study?

In T1b–T2a tumors, observed SLN positivity was 1.4% for patients predicted under 5% risk, indicating low nodal positivity. According to the company, the test achieved a TN:FN ratio of 73:1 in this subgroup versus the 19:1 guideline.

What TN:FN ratios did DecisionDx-Melanoma i31-SLNB achieve compared to NCCN thresholds for CSTL?

The i31-SLNB produced TN:FN ratios of 55:1 (T1–T2a) and 73:1 (T1b–T2a), both above the 19:1 guideline benchmark. According to the company, ratios above 19:1 indicate performance exceeding AJCC/NCCN guidance.

Will Castle Biosciences (CSTL) discuss the Future Oncology publication, and when is the webcast?

Yes. A live webcast will occur on March 23, 2026 at 4:30 p.m. ET to review the published data and host Q&A. According to the company, a replay will be available after the event on its investor site.

How does i31-SLNB compare to other predictive GEP tests like CP-GEP in the CSTL study?

The i31-SLNB showed higher TN:FN ratios versus previously reported CP-GEP (e.g., 55:1 vs 15:1 in T1–T2), indicating fewer missed positives. According to the company, this suggests improved low‑risk identification and fewer unnecessary SLNB procedures.