Castle Biosciences has announced new data validating the clinical utility of its DecisionDx-UM test for uveal melanoma (UM) patients, with findings presented at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting in Salt Lake City.
The study represents the first independent validation of the recently published Collaborative Ocular Oncology Group Study No. 2 (COOG2.1) and examined a real-world cohort of 1,297 patients with uveal melanoma, a rare but aggressive form of eye cancer.
"This real-world validation of the landmark COOG2.1 study both confirms the long-term performance of the DecisionDx-UM test and affirms the clinical value of PRAME as an adjunct biomarker that may further refine a patient's metastatic risk when combined with the DecisionDx-UM class result," said Rebecca Critchley-Thorne, Ph.D., vice-president of research and development at Castle Biosciences.
Enhanced Risk Stratification with PRAME Biomarker
The research specifically examined how adding Preferentially Expressed Antigen in Melanoma (PRAME) gene expression information to the DecisionDx-UM test result can further refine metastatic risk prediction. The findings demonstrate that co-reporting of DecisionDx-UM class and PRAME status provides additional insights into a patient's likelihood of metastasis.
The study validated that subdividing Class 1 and Class 2 tumors based on PRAME positive (+) versus negative (-) status offers more precise risk stratification. This approach enables clinicians to develop more tailored surveillance strategies and personalized treatment plans for patients with uveal melanoma.
The research was conducted through an ongoing collaboration with the National Cancer Institute's Surveillance, Epidemiology and End Results (NCI SEER) Program, which enabled linkage of UM patient records with their corresponding DecisionDx-UM and PRAME test results.
Clinical Significance of DecisionDx-UM
DecisionDx-UM is Castle Biosciences' 15-gene expression profile (GEP) test that uses an individual patient's tumor biology to predict individual risk of metastasis in patients with uveal melanoma. The test has become the standard of care in the management of newly diagnosed UM in the majority of ocular oncology practices in the United States.
Since 2009, the American Joint Committee on Cancer (AJCC) Staging Manual for UM has specifically identified the GEP test as a prognostic factor recommended for collection as part of clinical care. Additionally, the National Comprehensive Cancer Network (NCCN) guidelines for UM include the DecisionDx-UM test result as a prognostic method for determining metastasis risk.
The test has been validated in prospective, multi-center studies and has demonstrated superior prediction of metastasis compared to other prognostic factors, such as chromosome 3 status, mutational status, AJCC stage, and cell type. Currently, approximately 80% of patients diagnosed with UM in the United States receive the DecisionDx-UM test as part of their diagnostic workup.
Implications for Patient Care
This enhanced approach to risk stratification is designed to equip clinicians with more precise information to help guide surveillance strategies and enable more personalized treatment planning. The ultimate goal is to improve outcomes for patients with uveal melanoma by identifying those who may benefit from enhanced surveillance and management strategies.
"By combining the DecisionDx-UM class result with PRAME status, we can provide clinicians with a more comprehensive risk assessment tool," explained Dr. Critchley-Thorne. "This allows for more informed decision-making regarding follow-up care and potential interventions."
About Castle Biosciences
Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company focused on improving health through innovative tests that guide patient care. The company's current portfolio includes tests for skin cancers, Barrett's esophagus, and uveal melanoma.
In addition to its established diagnostic tests, Castle Biosciences has active research and development programs for tests in other diseases with high clinical need, including a test in development to help guide systemic therapy selection for patients with moderate-to-severe atopic dermatitis seeking biologic treatment.
The validation of DecisionDx-UM with PRAME biomarker represents an important advancement in the company's mission to transform disease management through precision diagnostics that prioritize patient outcomes.
