DecisionDx-Melanoma Test Predicts Nodal Positivity in Cutaneous Melanoma

The DecisionDx-Melanoma integrated sentinel lymph node biopsy (i31-SLNB) algorithm accurately predicted a low risk of nodal positivity in patients with cutaneous melanoma, according to a presentation from the 2026 Society of Surgical Oncology (SSO) Annual Meeting.¹

The prospective, multicenter study, which enrolled 912 patients across 30 US centers, was conducted to validate the test's ability to identify patients who may safely consider forgoing a sentinel lymph node biopsy (SLNB) while maintaining favorable clinical outcomes.

DecisionDx Findings

According to findings presented at the conference, patients were predicted to have a less than 5% risk of SLN positivity by the i31-SLNB test and had an actual nodal positivity rate of 2.6%. This performance remained consistent with the NCCN Cutaneous Melanoma Guidelines, which recommend avoiding SLNB if the predicted positivity rate is below 5%. Of note, in those with a greater than 10% risk of SLN positivity, the rate was 21.4%.

In the T1b-T2a patient subgroup, where clinical uncertainty regarding surgical staging is often highest, the i31-SLNB test identified a cohort with an actual nodal positivity rate of 1.4% (1/74). Patients with high-risk i31-SLNB results had an 18.5% SLN positivity rate.

Furthermore, patients with a low-risk i31-SLNB result demonstrated a 97.8% 3-year recurrence-free survival (RFS) rate.

“This study of DecisionDx-Melanoma’s i31-SLNB result confirms that the test delivers clear and clinically meaningful separation between low- and high-risk patients in real-world practice,” said Timothy Beard, MD, FACS, lead author of the SSO presentation and surgeon at Summit Medical Group in Bend, Oregon.¹ “Importantly, patients identified as low risk not only had very low rates of nodal positivity but also demonstrated high [RFS] over 3 years. That level of prospective validation can give clinicians and patients greater confidence when deciding whether to proceed with or forgo sentinel lymph node biopsy.”

DECIDE Trial Details

Data for the i31-SLNB algorithm were derived from a prospective, multicenter analysis, including findings from the DECIDE study. The DECIDE study was a prospective, multicenter, observational registry designed to evaluate the association of the DecisionDx-Melanoma gene expression profile (GEP) with the use of SLNB and subsequent clinical outcomes.

An analysis published in the World Journal of Surgical Oncology focused on a cohort of 322 patients with T1 to T2 tumors.² To assess the impact on clinical decision-making, researchers used propensity score-matching to compare these patients with a non-overlapping cohort where the 31-GEP was not utilized. In this specific analysis, no patients with a predicted risk of less than 5% had a positive SLNB (n = 0/35). The incorporation of i31-SLNB into the clinical workflow resulted in an 18.5% reduction in the number of SLNB procedures performed (43.7% vs 62.2%; P <.001). Investigators noted that the test could have potentially reduced the number of unnecessary biopsies by 25.0% (n = 35/140).

Patient Demographics

Overall, the median patient age was 63 years, 50.9% were male, and 86.3% saw a surgical oncologist. The most common T stages were T1a in 40.7% and T1b in 40.7%, and the most common tumor location was the extremity in 48.1%. An ulceration was not present in 90.1% of patients, and 52.2% had a less than 5% predicted risk. A SLN status was not performed in 56.5%.

Safety

The study reports highlighted that SLNB is an invasive surgical staging procedure with a reported complication rate of approximately 11%. By identifying patients with an actual nodal positivity rate of 2.6%—well below the 5% guideline threshold—the i31-SLNB test provided a validated method to avoid unnecessary surgical procedures and their associated complications. The high RFS observed in patients who did not undergo the procedure confirmed that forgoing SLNB based on the integrated GEP results did not compromise short-term oncologic safety. The test was developed to provide more precise risk estimation than American Joint Committee on Cancer (AJCC) staging alone, supporting risk-aligned shared decision-making.

References

1. DecisionDx®-Melanoma’s i31-SLNB: report from the largest prospective multicenter study to date confirms 2.6% nodal positivity in patients predicted to have less than 5% risk. News release. Castle Biosciences. March 9, 2026. Accessed March 11, 2026. https://tinyurl.com/3mv2bbr8
2. Guenther JM, Ward A, Martin BJ, et al. A prospective, multicenter analysis of the integrated 31-gene expression profile test for sentinel lymph node biopsy (i31-GEP for SLNB) test demonstrates reduced number of unnecessary SLNBs in patients with cutaneous melanoma. World J Surg Oncol. 2025;23(1):5. doi:10.1186/s12957-024-03640-x