Castle Biosciences (CSTL) Status update summary

Clinical context and test overview

• DecisionDx-Melanoma is a 31-gene expression profile test for Stage I-III melanoma, providing independent risk stratification for sentinel lymph node positivity and recurrence, supplementing traditional clinicopathologic factors.

• The test outputs include i31-SLNB (sentinel lymph node positivity risk) and i31-ROR (recurrence risk), each integrating gene expression with relevant clinical variables.

• DecisionDx-Melanoma has been validated in multiple retrospective, prospective, and real-world studies, consistently demonstrating robust risk separation and prognostic value.

DECIDE study design and objectives

• The DECIDE trial is a prospective, multicenter clinical utility study evaluating the i31-SLNB result's ability to guide sentinel lymph node biopsy decisions.

• Primary objectives: confirm i31-SLNB's predictive performance, assess its real-world impact on biopsy decisions, and track recurrence outcomes in patients with <5% predicted nodal risk.

• Enrolled 912 patients, median age 65, with a broad range of melanoma thickness and clinical features, reflecting real-world practice.

Key findings and clinical impact

• The test stratified patients into <5%, 5–10%, and >10% risk groups, with node positivity rates of 2.6%, 7%, and 21.4% respectively for all-comers, and 1.4% vs. 18.5% in Stage IB low vs. high risk.

• The assay outperformed both NCCN guidelines and competing GEP tests, with a 2.6% false negative rate overall and 1.8% in T1/T2a, and a high true negative to false negative ratio.

• Low-risk patients who avoided sentinel node biopsy had a 97.8% three-year recurrence-free survival, supporting safe de-escalation of care.

• The test identified high-risk biology even in shallow lesions, enabling more precise management and potentially life-saving interventions.