New Decision Modeling Study Demonstrates TissueCypher® Significantly Improves Risk-Aligned Management for Patients with Barrett's Esophagus

Decision modeling study shows use of TissueCypher can nearly double appropriate escalation of care for patients with non-dysplastic Barrett's esophagus who later progress to cancer, while substantially reducing overuse of procedures in patients who do not progress

FRIENDSWOOD, Texas, Sept. 15, 2026 /PRNewswire/ -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced the publication of a new decision modeling study showing that the TissueCypher® Barrett's Esophagus test (TSP-9) can help better align Barrett's esophagus (BE) management with a patient's individual risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). In the study, simulated use of TissueCypher significantly increased appropriate management aligned with known progression outcomes across patients with non-dysplastic BE (NDBE), indefinite for dysplasia (IND) and low-grade dysplasia (LGD). The study, titled "Clinical utility of the tissue systems pathology test for risk-aligned management of Barrett's esophagus: a decision modeling study," will be published in the Annals of Gastroenterology.¹

"The central challenge in managing patients with non-dysplastic Barrett's esophagus is that use of standard histology and clinical factors alone does not reliably distinguish the patients who are likely to progress from the many who will not," said Lucas C. Duits, M.D., Ph.D., gastroenterologist at Amsterdam University Medical Centers and co-first author of the study. "That gap is exactly the problem TissueCypher was designed to address. These findings show that incorporating TissueCypher into clinical decision-making can help us identify the higher-risk patients earlier, when closer surveillance or endoscopic eradication therapy may have the greatest opportunity to change the course of their disease."

BE is a pre-malignant condition that can progress to EAC, a cancer with poor long-term survival. Despite widespread endoscopic surveillance programs and the availability of endoscopic eradication therapy (EET) to effectively treat dysplasia and early cancer, EAC incidence and mortality have remained largely unchanged. A key challenge is that standard histology and clinical factors alone cannot accurately identify which patients with BE are at high risk of progression, particularly those with NDBE. Although patients with NDBE are typically considered to be at lower risk of progression, they make up approximately 89% of patients in the U.S. undergoing surveillance for BE, and roughly half of patients who progress to cancer were initially diagnosed with NDBE.

"Overuse of surveillance endoscopy is a real and recognized problem in Barrett's management, and this study shows that better risk stratification may help reduce it," added Duits. "By identifying patients at lower risk of progression, TissueCypher can support shared decision-making between clinicians and patients, helping avoid unnecessary procedures while preserving appropriate escalation for patients who are more likely to progress."

The study, led by co-first authors Lucas C. Duits, M.D., Ph.D., and Amir M. Khoshiwal, M.D., Ph.D., of Amsterdam University Medical Centers, together with collaborators at the University of Pittsburgh, Cleveland Clinic, Geisinger Medical Center and the University of Pennsylvania, used a clinical decision-tree model to simulate patient management with and without guidance from TissueCypher test results. The analysis pooled data from 699 patients across five published clinical validation studies, each with known progression or non-progression outcomes.

Key Findings

• Across all of the patients with BE in the study (NDBE, IND and LGD), incorporating TissueCypher results into management decisions would have significantly increased the percentage of patients receiving appropriate management from 59.8% to 75.3% (P<0.001).
• Among all progressors to HGD or EAC, modeling indicated that TissueCypher-guided management would have increased the percentage of patients who received appropriate escalation to short-interval surveillance or EET from 50.5% to 66.3% (P=0.008), representing a 31.9% reduction in undertreatment. Across all non-progressors, TissueCypher would have delivered a 41.7% reduction in overtreatment (P<0.001).
• The impact of TissueCypher-guided management was most pronounced in patients with NDBE who later progressed to HGD or EAC, a group often missed by the current standard of care. In these patients, use of TissueCypher would have nearly doubled the percentage of patients appropriately escalated to short-interval surveillance or EET from 30.4% to 56.9% (P=0.001). Among patients with NDBE who did not progress, appropriate management would have also improved significantly from 71.0% to 84.5% (P<0.001), reflecting a meaningful reduction in unnecessary procedures.
• In patients with IND or LGD, TissueCypher-guided management would have significantly increased appropriate management for non-progressors from 53.0% to 70.8% (P<0.001), without leading to undertreatment of patients who progressed to HGD/EAC.

In this modeling study, clinical utility was consistently demonstrated across clinically relevant NDBE subgroups, including patients with both short-segment BE (considered clinically lower risk) and long-segment BE, highlighting the broad applicability of the TissueCypher test. Together, these findings underscore TissueCypher's ability to support more individualized BE management by helping clinicians escalate care for patients at higher risk of progression while avoiding unnecessary procedures for those at lower risk.

About TissueCypher Barrett's Esophagus Test
TissueCypher is a precision medicine test designed and extensively validated to predict a patient's personalized risk of progression from Barrett's esophagus (BE) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Indicated for patients with non-dysplastic BE, indefinite for dysplasia or with low-grade dysplasia, TissueCypher's five-year risk assessment is designed to help physicians tailor care to each patient's risk of developing HGD or EAC.

Backed by more than 17 peer-reviewed publications and studied in biopsies from more than 8,000 patients, TissueCypher has been shown to be the strongest independent predictor of progression compared with traditional histopathological risk assessment. Using an AI-derived spatialomics approach, the test identifies molecular signatures that often precede the development of dysplasia, which can enable earlier identification, treatment, and management of patients at increased risk of cancer. TissueCypher is designed to integrate seamlessly into routine endoscopic practice by analyzing standard esophageal pinch biopsies, delivering actionable insights without requiring additional procedures. Learn more at CastleBiosciences.com/TissueCypher.

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: TissueCypher's ability to (i) support more individualized BE management and (ii) help clinicians escalate care for patients at higher risk of progression while avoiding unnecessary procedures for those at lower risk. The words "believe," "can," "may," "would" 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, 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. Duits LC, Khoshiwal AM, Davison JM, et al. Clinical utility of the tissue systems pathology test for risk aligned management of Barrett's esophagus: a decision modeling study. Ann Gastroenterol. 2026. doi:10.20524/aog.2026.1100

Investor Contact:
Camilla Zuckero 
[email protected]

Media Contact:
Allison Marshall
[email protected]

SOURCE Castle Biosciences, Inc.