Gene Expression Test Refines Melanoma Biopsy Decision-Making

Clinicians need decision-support tools that more precisely estimate the likelihood of sentinel lymph node involvement, helping avoid unnecessary operations while identifying those who may benefit from surgery. A newly published prospective study reports that an integrated 31-gene expression profile–based result more accurately stratifies sentinel lymph node positivity risk and may help identify patients who can safely forgo biopsy.

DecisionDx-Melanoma’s integrated sentinel lymph node biopsy result, i31-SLNB, from Castle Biosciences combines a 31-gene expression profile (31-GEP) score with select clinicopathologic variables to generate a personalized probability of sentinel lymph node (SLN) positivity. The test analyzes tumor biology in patients with stage I–III cutaneous melanoma and also provides a separate risk estimate for recurrence and/or metastasis. This information is designed to guide SLNB consideration, follow-up intensity, imaging, and referrals.

In a prospective, multicenter cohort published in Dermatology and Therapy, investigators compared i31-SLNB with the Melanoma Institute Australia (MIA) clinicopathologic-only nomogram in 912 patients considering SLNB within the DECIDE study. The analysis used National Comprehensive Cancer Network (NCCN) decision thresholds for SLN positivity: less than 5% to avoid SLNB, 5–10% to consider SLNB, and more than 10% to offer SLNB. Outcomes were evaluated by observed SLN positivity within each risk stratum and by overall discriminative performance.

Patients classified as low risk by i31-SLNB had a 2.6% observed SLN positivity rate, below the 5% NCCN threshold. By comparison, patients classified as low risk by the MIA nomogram had a 5.8% observed positivity rate, meaning the nomogram did not identify a subgroup below the 5% threshold. In discordant cases, patients deemed low risk by i31-SLNB but higher risk by MIA had a 2.8% observed positivity rate, while those deemed low risk by MIA but higher risk by i31-SLNB had an 11.5% positivity rate. Overall, i31-SLNB showed stronger discrimination than the MIA nomogram, with an area under the curve (AUC) of 0.74 versus 0.61 (p=0.001).

Given that up to 88% of SLNB procedures are negative and approximately 15% of patients experience surgery-associated complications, the study highlights the need for more accurate preoperative risk assessment. The findings add to prospective evidence that integrating tumor biology with clinicopathologic features improves identification of both low‑ and high‑risk patients. Earlier multicenter work cited in the company's announcement similarly showed the approach outperforming a clinicopathologic-only nomogram.

“Many clinicians are familiar with nomograms that estimate risk of sentinel lymph node positivity using clinicopathologic features alone, yet current guidelines acknowledge limitations in their performance at lower risk thresholds,” said Rohit Sharma, M.D., FACS, lead author of the study and surgical oncologist at Marshfield Clinic Health System in Marshfield, Wisconsin.

“Because of this, accurately identifying which patients are unlikely to have sentinel lymph node involvement remains an important challenge in melanoma care. The study findings demonstrate that incorporating tumor biology through DecisionDx-Melanoma's i31-SLNB test result can improve risk assessment, helping clinicians better distinguish which patients with melanoma may safely avoid SLNB and which should consider having the surgery.” 

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