Landmark Study Shows Combination of Castle Biosciences' DecisionDx®-UM and PRAME Outperforms Gene Mutation Analysis in Predicting Survival Outcomes in Uveal Melanoma

Rhea-AI Summary

Castle Biosciences (Nasdaq: CSTL) reported new data from the largest prospective, multicenter study comparing NGS-based mutation analysis with the combination of DecisionDx-UM + PRAME for predicting outcomes in uveal melanoma (UM). Published Dec. 17, 2025, the COOG study analyzed 1,140 primary UM tumors and found that DecisionDx-UM + PRAME provided superior predictions of metastasis-free survival (MFS) and overall survival (OS) versus individual NGS mutation analysis. BAP1, SF3B1 and EIF1AX mutations lost independent predictive significance when DecisionDx-UM + PRAME were included in multivariate models. Castle offers DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq from one biopsy to support risk stratification and treatment planning.

Positive

• Study size: 1,140 primary UM tumors analyzed
• Clinical performance: DecisionDx-UM + PRAME outperformed NGS for MFS and OS
• Integrated offering: Three tests (DecisionDx-UM, PRAME, UMSeq) from one biopsy

Negative

• NGS prognostic value reduced: BAP1/SF3B1/EIF1AX lost independent significance in multivariate analysis

Key Figures

Primary UM tumors analyzed 1,140 tumors Prospective multicenter uveal melanoma study

Small early-stage tumors 131 tumors Subset of primary uveal melanoma tumors

Mutation clusters 7 clusters Recurrent genetic mutation clusters assessed by NGS

UM tests offered 3 tests DecisionDx-UM, DecisionDx-PRAME, DecisionDx-UMSeq from one biopsy

Market Reality Check

$39.60 Last Close

Volume Volume 309,691 is below the 20-day average of 464,542 (relative volume 0.67). low

Technical Price $39.05 is above the 200-day MA of $22.59 and 3.84% below the 52-week high.

Peers on Argus

CSTL was up 0.44% with peers mixed: FLGT slightly positive while CDNA, MYGN, PSNL and NEO were negative, indicating stock-specific strength rather than a broad sector move.

Common Catalyst Both CSTL and PSNL had publications highlighting advanced molecular testing in oncology, pointing to ongoing innovation in cancer diagnostics.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 12	Clinical validation data	Positive	+1.7%	Meta-analysis confirmed TissueCypher risk stratification superiority versus traditional methods.
Dec 09	Clinical practice endorsement	Positive	+0.4%	Expert panel endorsed DecisionDx-Melanoma as best-practice prognostic tool.
Nov 17	Corporate recognition	Positive	+1.5%	Fifth consecutive Top Workplaces award and multiple culture recognitions.
Nov 14	Clinical data update	Positive	-2.0%	New DecisionDx-Melanoma data improved SLNB decision-making and prognosis.
Nov 11	Conference participation	Neutral	+0.7%	Announcement of presentation at Piper Sandler healthcare conference.

Pattern Detected

Recent positive scientific and corporate news has typically produced modest, mostly positive single-day moves, with one notable divergence on favorable melanoma data.

Recent Company History

Over the last months, Castle Biosciences highlighted multiple data-driven milestones. On Nov 14, 2025, new DecisionDx-Melanoma data slightly coincided with a -1.96% move despite positive findings. Subsequent news on workplace awards, expert endorsement of DecisionDx-Melanoma, and a TissueCypher meta-analysis on Dec 12, 2025 all saw small positive reactions (up to 1.74%). Today’s uveal melanoma study continues this pattern of peer‑reviewed validation across the test portfolio.

Market Pulse Summary

This announcement highlights new prospective data in uveal melanoma showing the combination of DecisionDx‑UM and PRAME outperformed NGS‑based mutation analysis in predicting metastasis-free and overall survival across 1,140 tumors. It extends a string of peer‑reviewed validations across Castle’s portfolio. Investors may track future adoption trends for these tests, additional publications, and how this clinical evidence supports broader use of Castle’s three UM assays from a single biopsy sample.

Key Terms

next-generation sequencing (ngs) technical

"comparing next-generation sequencing (NGS)-based gene mutation analysis with the combination"

A laboratory technique that reads the sequence of DNA or RNA by processing millions of fragments at once, like scanning many pages of a book simultaneously instead of one at a time. It matters to investors because it accelerates and lowers the cost of genetic testing, drug discovery and diagnostics, expanding markets for biotech, diagnostics equipment and data services and enabling products that can change clinical care and revenue streams.

uveal melanoma medical

"predicting outcomes in patients with uveal melanoma (UM). The study, titled"

A cancer that starts in the uveal tract of the eye — the iris, ciliary body or choroid — growing like an unwanted patch in the eye’s colored and surrounding tissues. It matters to investors because its rarity and serious course mean that successful drugs, surgical techniques, or diagnostic tests can shift patient care, regulatory approvals, and revenue prospects for healthcare companies in the oncology and ophthalmology markets.

metastasis-free survival medical

"shows that the combination of DecisionDx-UM and PRAME delivers superior predictions of metastasis-free survival"

Metastasis-free survival is the length of time after treatment during which a patient shows no signs that cancer has spread to other parts of the body. For investors, it’s a key clinical measure of a drug’s effectiveness — like how long a repair keeps a leak from returning — because longer metastasis-free survival can improve chances of regulatory approval, support stronger sales forecasts, and reduce future treatment costs.

overall survival medical

"superior predictions of metastasis-free survival and overall survival compared to NGS-based"

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

gene expression medical

"with the combination of DecisionDx-UM and Preferentially Expressed Antigen in Melanoma (PRAME) gene expression for predicting"

Gene expression is the process by which a cell reads a gene’s instructions and produces the molecules—usually proteins—that do work in the body, like building structures or sending signals. Think of a gene as a recipe and expression as the act of cooking: whether and how much a dish gets made affects the final product. Investors care because changes in gene expression underlie diseases, treatment responses, biomarkers and drug targets, so they can influence clinical outcomes, regulatory decisions and commercial value.

multivariate analysis technical

"became non-significant and redundant when DecisionDx-UM + PRAME were included in multivariate analysis."

A statistical approach that examines several variables at once to see how they relate to each other and to an outcome, such as returns, risk, or sales. For investors it helps separate the influence of different factors—like market trends, company size, or interest rates—so you can identify which ones drive performance and make more informed forecasts and risk assessments. Think of it as tasting a stew to judge which ingredients matter most to the final flavor.

tumor microenvironment medical

"which provides a more comprehensive view of the tumor microenvironment. Conversely, targeted NGS"

The tumor microenvironment is the immediate area surrounding a cancer cell, made up of nearby cells, blood vessels, and support structures that influence how the cancer grows and spreads. It functions like a bustling neighborhood that can either help or hinder the tumor’s development. For investors, understanding changes in this environment can signal the effectiveness of treatments and potential shifts in a cancer-related market.

tumor cells medical

"measure gene activity from both tumor cells and surrounding immune cells, which provides"

Tumor cells are abnormal body cells that grow into a lump or mass and can crowd out healthy tissue or, in some cases, spread to other parts of the body—like weeds in a garden that multiply and overtake nearby plants. They matter to investors because treatments, tests, or devices aimed at detecting, shrinking or eliminating these cells drive clinical trial outcomes, regulatory approvals and revenue potential; progress or setbacks in that work can quickly change a healthcare company's valuation.

AI-generated analysis. Not financial advice.

FRIENDSWOOD, Texas, Dec. 17, 2025 (GLOBE NEWSWIRE) -- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced new data from the largest prospective, multicenter study to date comparing next-generation sequencing (NGS)-based gene mutation analysis with the combination of DecisionDx-UM and Preferentially Expressed Antigen in Melanoma (PRAME) gene expression for predicting outcomes in patients with uveal melanoma (UM). The study, titled “Early Genetic Evolution of Driver Mutations in Uveal Melanoma,” was conducted by the Collaborative Ocular Oncology Group (COOG) and recently published in Nature Communications.

"The recently published COOG2 study validated that combining DecisionDx-UM test results and PRAME gene expression data provides more precise metastatic risk prediction for patients with UM than either test used independently," said J. William Harbour, M.D., ocular oncologist, and professor and chair of the Department of Ophthalmology at UT Southwestern Medical Center in Dallas.¹ "Our latest research builds on these findings and shows that the combination of DecisionDx-UM and PRAME delivers superior predictions of metastasis-free survival and overall survival compared to NGS-based mutation analysis. While gene mutation analysis remains valuable for other purposes, such as confirming tumor sampling quality and identifying patients for appropriate clinical trials, the DecisionDx-UM + PRAME combination offers the most comprehensive risk stratification available to guide more informed treatment pathway decisions for patients with UM.”

UM is a rare but aggressive eye cancer with a high risk of metastasis, often leading to fatal outcomes. Notably, UM tumors are most likely to spread when they are still small, making them difficult to distinguish from benign lesions during early detection. This study aimed to better understand the genetic changes that drive the progression from benign nevi to malignant melanoma at the molecular level. Researchers analyzed 1,140 primary UM tumors, including 131 small, early-stage tumors, using NGS to assess seven clusters of recurrent genetic mutations. They then compared the predictive accuracy of these mutations with the combined DecisionDx-UM + PRAME result in assessing metastatic risk.

Key findings of the study include:

• DecisionDx-UM + PRAME, when used together, provide superior predictions of both metastasis-free survival (MFS) and overall survival (OS) when compared to individual gene mutation analysis using NGS.
• While the BAP1, SF3B1 and EIF1AX gene mutations were individually associated with high, medium and low metastatic risk (respectively), their ability to predict both MFS and OS became non-significant and redundant when DecisionDx-UM + PRAME were included in multivariate analysis.
• The study authors attribute the superior performance of DecisionDx-UM + PRAME to DecisionDx-UM’s ability to measure gene activity from both tumor cells and surrounding immune cells, which provides a more comprehensive view of the tumor microenvironment. Conversely, targeted NGS analyzes DNA mutations in tumor cells alone. By capturing this broader biological context, DecisionDx-UM is designed to offer a more accurate assessment of a tumor’s potential to metastasize.
  

Castle currently offers three tests for patients with UM – DecisionDx-UM, DecisionDx^®-PRAME and DecisionDx^®-UMSeq, an NGS-based test – all from a single biopsy sample. Together, these tests provide the most comprehensive molecular insights currently available on the market for patients with UM, supporting precise risk assessment and informed treatment planning.

About the Collaborative Ocular Oncology Group
The Collaborative Ocular Oncology Group (COOG) is the largest collaborative working group in North America of ocular and medical oncologists specialized in the treatment of patients with intraocular cancers, currently focusing on uveal melanoma. The COOG comprises more than 25 leading academic and private ocular oncology centers of excellence and has been continually funded by the National Cancer Institute for over a decade. The COOG has conducted two large multicenter prospective studies of prognostic biomarkers in uveal melanoma, the first and only such studies ever conducted in this cancer, and is planning a major expansion into adjuvant and metastatic clinic trials in patients with uveal melanoma.

About DecisionDx-UM
DecisionDx-UM is a gene expression profile (GEP) test that uses a patient’s tumor biology to predict their personalized risk of metastasis from uveal melanoma, a rare and aggressive eye cancer. By stratifying patients into low-, intermediate- or high-risk groups, the test helps guide personalized care decisions, including surveillance intensity, medical oncology referral and clinical trial consideration. Since 2009, DecisionDx-UM has been widely adopted as the standard of care in the U.S. and is included in the American Joint Committee on Cancer (AJCC) Staging Manual and the National Comprehensive Cancer Network (NCCN) Guidelines. The test is supported by more than 25 peer-reviewed publications involving more than 5,000 patients, representing the largest evidence base of any prognostic test for uveal melanoma. Today, nearly 80% of newly diagnosed patients undergo DecisionDx-UM testing. 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, 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 clinical utility and performance of our diagnostic tests, including DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq; the ability of the DecisionDx-UM + PRAME combination test to guide more informed, risk-aligned management decisions through the precise risk-stratification of patients with UM; and the potential increased risk stratification from including PRAME gene expression information to a patient’s DecisionDx-UM test result. The words “believe,” “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 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. Harbour JW, Correa ZM, Schefler AC, et al. 15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1). J Clin Oncol. 2024;42(28):3319-3329. doi:10.1200/JCO.24.00447
   

Investor Contact:
Camilla Zuckero
czuckero@castlebiosciences.com

Media Contact:
Allison Marshall
amarshall@castlebiosciences.com

FAQ

What did Castle Biosciences (CSTL) announce on December 17, 2025 about DecisionDx-UM and PRAME?

Castle announced COOG study data showing DecisionDx-UM + PRAME outperformed NGS mutation analysis for predicting MFS and OS in uveal melanoma.

How many tumor samples were analyzed in the COOG study cited by Castle Biosciences (CSTL)?

Researchers analyzed 1,140 primary uveal melanoma tumors, including 131 small early-stage tumors.

What is the clinical implication of DecisionDx-UM + PRAME outperforming NGS for CSTL investors?

The data support DecisionDx-UM + PRAME as a more precise risk stratification tool, potentially increasing clinical adoption of Castle’s molecular testing suite.

Does Castle Biosciences (CSTL) still offer NGS testing after the COOG study results?

Yes; Castle continues to offer DecisionDx-UMSeq (NGS) alongside DecisionDx-UM and DecisionDx-PRAME from a single biopsy sample.

Which gene mutations were compared with DecisionDx-UM + PRAME in the study referenced by Castle (CSTL)?

The study evaluated recurrent mutations including BAP1, SF3B1 and EIF1AX and seven mutation clusters.