Systematic Review and Meta-Analysis Confirms TissueCypher® Outperforms Traditional Pathology or Clinical Factors Alone to Identify Patients at Increased Risk of Developing Esophageal Cancer

Rhea-AI Summary

Castle Biosciences (Nasdaq: CSTL) announced a December 12, 2025 systematic review and meta-analysis in Journal of Clinical Gastroenterology showing the TissueCypher Barrett’s Esophagus test provides validated risk stratification versus pathology or clinical factors alone.

The SRMA pooled six published studies and found high-risk TissueCypher results were 6.7x more likely to progress to high-grade dysplasia or esophageal adenocarcinoma within five years (p<0.0001). Annual progression rates were 5.6% for high-risk and 2.8% for high/intermediate-risk, both above a 1.7% LGD benchmark.

Positive

• 6.7x higher five-year progression risk for high-risk results
• High-risk 5.6% annual progression rate
• High/intermediate-risk 2.8% annual progression rate
• Meta-analysis pooled six published studies confirming consistency

Negative

• None.

News Market Reaction

+1.74%

1 alert

+1.74% News Effect

On the day this news was published, CSTL gained 1.74%, reflecting a mild positive market reaction.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Studies included: 6 studies Progression risk increase: 6.7 times Follow-up period: 5 years +4 more

7 metrics

Studies included 6 studies Systematic review and meta-analysis of TissueCypher performance

Progression risk increase 6.7 times High-risk vs low-risk TissueCypher results over five years

Follow-up period 5 years Progression to HGD or EAC comparison window

Statistical significance p<0.0001 Difference in progression risk between high- and low-risk results

Annual progression (high/intermediate) 2.8% per year Patients with high or intermediate TissueCypher risk results

Annual progression (high risk) 5.6% per year Patients with high-risk TissueCypher results

LGD benchmark rate 1.7% per year Typical annual progression rate reported for LGD patients

Market Reality Check

Price: $42.84 Vol: Volume 510,365 is 1.09x t...

normal vol

$42.84 Last Close

Volume Volume 510,365 is 1.09x the 20-day average of 468,205 shares ahead of this news. normal

Technical Shares at $37.97 were trading above the 200-day MA of $22.35, and about 6.5% below the 52-week high.

Peers on Argus

Pre-news moves in key diagnostics peers were mixed, with FLGT and PSNL down whil...

Pre-news moves in key diagnostics peers were mixed, with FLGT and PSNL down while CDNA and MYGN were up. NEO also declined, suggesting no unified sector trend around this announcement.

Historical Context

5 past events · Latest: Dec 09 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 09	Clinical endorsement	Positive	+0.4%	Expert panel endorsed DecisionDx-Melanoma as best-practice prognostic tool.
Nov 17	Workplace award	Positive	+1.5%	Fifth consecutive Houston Chronicle Top Workplaces recognition and multiple culture awards.
Nov 14	Clinical data update	Positive	-2.0%	New data showed DecisionDx-Melanoma improved SLNB decisions and prognostic accuracy.
Nov 11	Conference participation	Positive	+0.7%	Management scheduled to present company overview at Piper Sandler healthcare conference.
Nov 03	Earnings and guidance	Positive	+1.9%	Q3 2025 results beat prior guidance with raised full‑year outlook and strong test volumes.

Pattern Detected

Recent fundamentally positive news has generally seen modestly positive price alignment, with one notable divergence on clinical data.

Recent Company History

Over the last six weeks, Castle Biosciences reported multiple positive developments, including Q3 2025 revenue of $83.0 million with raised full‑year guidance, new clinical data reinforcing DecisionDx‑Melanoma utility, and expert endorsement of that test as best practice. The company also highlighted workplace culture recognition and conference participation. Price reactions were mostly small positive moves, with one negative reaction to favorable melanoma data. Today’s Barrett’s esophagus SRMA publication extends the pattern of clinical-validation news for the company’s test portfolio.

Market Pulse Summary

This announcement details a systematic review and meta-analysis of 6 studies validating TissueCypher...

Analysis

This announcement details a systematic review and meta-analysis of 6 studies validating TissueCypher for Barrett’s esophagus, showing high-risk results confer a 6.7-fold higher progression risk and annual rates up to 5.6% versus a 1.7% LGD benchmark. It extends Castle’s pattern of data-driven support for its test portfolio. Investors may track future adoption metrics, reimbursement developments, and additional outcomes data to gauge how this evidence translates into volumes and revenue alongside recent earnings momentum.

Key Terms

systematic review and meta-analysis, risk stratification, Barrett’s esophagus, high-grade dysplasia, +4 more

8 terms

systematic review and meta-analysis medical

"announced the publication of a new systematic review and meta-analysis (SRMA)"

A systematic review and meta-analysis gathers all credible studies on a specific clinical or scientific question, checks their quality, and then pools the numerical results to produce a single best estimate of the effect. For investors, this provides a clearer, more reliable picture of whether a medicine, device, or strategy actually works and how large the benefit or risk is—think of it as averaging many product reviews after removing poor-quality or irrelevant ones.

risk stratification medical

"demonstrating that the TissueCypher Barrett’s Esophagus test provides clinically validated risk stratification"

Grouping people, projects or assets by their likelihood of a negative outcome—such as disease progression, regulatory problems, loan default or product failure—so decisions can be tailored to each group's risk level. Like sorting mail by urgency, risk stratification helps investors gauge which opportunities are safer or more speculative, adjust expected returns, prioritize resources, and estimate how likely different financial or regulatory outcomes are.

Barrett’s esophagus medical

"for patients with Barrett’s esophagus (BE). The findings confirm"

A condition in which the normal lining of the lower esophagus is replaced by tissue more like the intestine, often from long-term acid reflux. It matters to investors because it increases the chance of developing esophageal cancer, driving demand for screening tests, medical procedures and drug development; like a warning light on a car, it signals greater need for medical care and possible regulatory activity that can affect healthcare company revenues.

high-grade dysplasia medical

"greater risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma"

High-grade dysplasia is a severe abnormal change in cells of a tissue that looks much closer to cancer than normal cells and carries a high risk of becoming invasive cancer if not treated. For investors, it matters because diagnosis, treatment, or clinical trial results involving high-grade dysplasia can directly affect regulatory decisions, projected medical costs, market demand for therapies, and the commercial outlook for companies developing diagnostics or treatments—much like spotting deep cracks in a building that require urgent repair.

esophageal adenocarcinoma medical

"progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC)"

Esophageal adenocarcinoma is a form of cancer that begins in the gland-like cells lining the lower part of the esophagus, the tube that carries food to the stomach. It matters to investors because it is often aggressive and has limited treatment options, so advances, trial results, regulatory approvals, or changes in insurance coverage for new tests and therapies can materially affect the prospects and valuations of companies working on diagnostics, drugs, or procedures—like a bridge repair changing traffic for nearby businesses.

histologic assessment medical

"shows that the test outperforms histologic assessment in identifying patients"

Histologic assessment is the microscopic examination of tissue samples to see how cells and structures look and respond to disease or treatment, much like a mechanic inspecting engine parts to find wear or damage. For investors, these findings help show whether a drug or medical device is working, safe, or causing harm, and they can influence clinical trial outcomes, regulatory decisions, and future revenue prospects.

non-dysplastic BE medical

"across patients with non-dysplastic BE (NDBE), indefinite for dysplasia (IND)"

A non-dysplastic Barrett’s esophagus is a change in the lining of the esophagus where cells look abnormal under the microscope but show no precancerous (dysplastic) changes. It matters to investors because it defines a large, monitored patient group that typically needs regular check-ups and diagnostic tests — like a stretched warranty period — influencing demand for surveillance endoscopy, diagnostic tools, drugs, and follow-up care without immediate surgical or oncologic intervention.

low-grade dysplasia medical

"indefinite for dysplasia (IND) and low-grade dysplasia (LGD), and shows"

Low-grade dysplasia describes a cluster of cells that look abnormal under a microscope but are not cancer; think of them as slightly cracked tiles that signal wear and a chance of bigger damage over time. For investors, its presence matters because it raises the likelihood of future disease progression, influences clinical trial outcomes and regulatory decisions, and drives demand for monitoring, treatments, or diagnostic tools tied to related healthcare markets.

AI-generated analysis. Not financial advice.

Across multiple published studies, the test consistently identifies high-risk patients whose progression rates exceed guideline-based actionable thresholds for intensified care

FRIENDSWOOD, Texas, Dec. 12, 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 systematic review and meta-analysis (SRMA) demonstrating that the TissueCypher^® Barrett’s Esophagus test provides clinically validated risk stratification for patients with Barrett’s esophagus (BE). The findings confirm that TissueCypher can outperform traditional pathology or clinical factors alone to identify patients at increased risk of developing esophageal cancer.

The paper, titled “The Tissue Systems Pathology Test Predicts Risk of Progression in Patients With Barrett’s Esophagus: Systematic Review and Meta-Analysis,” was published in the Journal of Clinical Gastroenterology. The analysis consolidated data from six previously published studies and found that TissueCypher consistently identifies patients at greater risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), a key step toward enabling personalized, risk-aligned patient management aimed at preventing cancer.

“Our findings provide strong evidence that TissueCypher delivers meaningful risk stratification for patients with Barrett’s esophagus,” said Caitlin C. Houghton, M.D., board-certified foregut surgeon at Keck Medicine of USC in Los Angeles, California, and lead author of the study. “By identifying which patients are truly at high risk for progression to esophageal cancer — and which are not — TissueCypher can help physicians personalize care, flagging those who may benefit from earlier intervention and providing confidence in continuing routine surveillance for those at low risk.”

SRMAs represent rigorous, high-quality evidence for clinical validation because they synthesize findings across multiple studies to provide overall estimates of performance. The results of this SRMA represent the most comprehensive validation of the TissueCypher test to date, reinforcing its value as an evidence-based tool for risk stratification in BE. The study demonstrates TissueCypher’s predictive performance across patients with non-dysplastic BE (NDBE), indefinite for dysplasia (IND) and low-grade dysplasia (LGD), and shows that the test outperforms histologic assessment in identifying patients at greatest risk of progression.

Key findings of the SRMA indicate TissueCypher can help physicians:

• Identify patients at highest risk: Across six published studies, patients with high-risk TissueCypher results were 6.7 times more likely to progress to HGD or EAC within five years than those with low-risk results (p<0.0001).
• Guide care with confidence: Patients with high or intermediate-risk results had an annual progression rate of 2.8%, and those with high-risk results had a rate of 5.6% per year, both above the 1.7% annual progression rate typically reported for patients with LGD, a clinical benchmark for therapeutic intervention.

By integrating data across multiple studies, this analysis confirms that TissueCypher provides consistent, reproducible performance and supports its potential to help physicians deliver risk-aligned care, identifying patients most likely to progress and tailoring management strategies that can improve outcomes while reducing unnecessary procedures.

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 to high-grade dysplasia or esophageal adenocarcinoma. 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 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-driven 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 www.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, 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 provide risk insights beyond pathology or clinical factors alone and enable more personalized surveillance and treatment strategies for BE patients that may help prevent cancer, including supporting earlier intervention for those at higher risk for progression to esophageal cancer, reducing unnecessary procedures for those at lower risk of progression, and supporting risk-aligned management of patients with a finding of indefinite for dysplasia. The words “believe,” “may,” “can” 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 our Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, each as 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.

Investor Contact:
Camilla Zuckero
czuckero@castlebiosciences.com

Media Contact:
Allison Marshall
amarshall@castlebiosciences.com

Source: Castle Biosciences, Inc.

FAQ

What did Castle Biosciences announce about TissueCypher on December 12, 2025 (CSTL)?

Castle Biosciences announced a SRMA showing TissueCypher outperforms pathology or clinical factors alone in predicting progression to HGD or EAC.

How much greater was progression risk for high-risk TissueCypher results in the SRMA (CSTL)?

Patients with high-risk TissueCypher results were 6.7 times more likely to progress to HGD or EAC within five years (p<0.0001).

What annual progression rates did the SRMA report for TissueCypher high-risk and intermediate/high-risk groups (CSTL)?

The SRMA reported an annual progression rate of 5.6% for high-risk results and 2.8% for high or intermediate-risk results.

How many studies were included in the TissueCypher meta-analysis published December 12, 2025 (CSTL)?

The systematic review and meta-analysis consolidated data from six previously published studies.

Does the SRMA suggest TissueCypher can change clinical management for Barrett’s esophagus patients (CSTL)?

The SRMA indicates TissueCypher can help personalize care by identifying patients likely to progress who may need earlier intervention and those who may continue routine surveillance.