Research Summary:
Sentinel lymph node biopsy (SLNB) is a standard procedure for staging and management in patients with cutaneous melanoma, aimed at assessing the presence of metastasis in regional lymph nodes. However, SLNB is associated with potential risks and high costs, necessitating accurate patient selection. The National Comprehensive Cancer Network (NCCN) guidelines recommend SLNB for patients with a SLN positivity risk greater than 10 percent, advise that SLNB be considered for those with a 5 to 10 percent risk, and advise against it for patients with a less than five-percent risk. Besides low (Class 1A), intermediate (Class 1B/2A), and high (Class 2B) 31-gene expression profile (GEP) risk class, the DecisionDx-Melanoma report now additionally provides an integrated SLN positivity percentage risk score (i31-SLNB) determined via a neural network algorithm combining the patient’s 31-GEP score with select clinicopathologic features, thus potentially refining the selection process for SLNB.
Guenther et al1 conducted the prospective, multicenter DecisionDx-Melanoma Impact on Sentinel Lymph Node Biopsy Decision and Clinical Outcomes (DECIDE) study to evaluate the accuracy and clinical utility of the i31-SLNB algorithm in predicting SLN positivity among patients with T1 to T2 cutaneous melanoma. The study evaluated whether considering the i31-SLNB test result could improve patient selection for SLNB and reduce the number of unnecessary procedures while maintaining diagnostic accuracy.
A total of 322 patients from multiple centers were enrolled and underwent the i31-SLNB test to assess their risk of SLN positivity. The inclusion criteria required patients to have newly diagnosed invasive cutaneous melanoma and to be considering SLNB. Patients with T1a tumors were included if they had at least one high-risk feature, such as mitotic rate of 2/mm2 or greater, lymphovascular invasion, or absence of tumor-infiltrating lymphocytes. Patients with T1b to T2 tumors were also included. Exclusion criteria included stage III to IV melanoma at diagnosis, history of a prior diagnosis at the same location as current primary melanoma, and having already undergone SLNB; patients were also excluded if the clinician ordered the 31-GEP test for a reason exclusively other than guidance for SLNB decision-making.2
Median patient age was 63 years, and 50.9 percent of patients were male. Most patients had T1a or T1b tumors (both n=131, 40.7%). Fifty-one patients (15.8%) had T2a tumors, and nine (2.8%) had T2b tumors. Of the 322 included patients, 140 (43.5%) underwent SLNB, of whom nine (6.4%) had a positive SLN.
A comparison between the DECIDE study cohort and a propensity score–matched historical cohort where the i31-SLNB was not utilized for SLNB decision-making showed an 18.5-percent reduction in SLNB procedures with i31-SLNB testing (43.7% vs. 62.2%; p<0.001). This reduction indicates that incorporating the i31-SLNB into clinical decision-making might decrease unnecessary SLNB procedures while maintaining patient safety.
Researchers found that none of the patients predicted to have a <5% risk of SLN positivity by the i31-SLNB (n=35) had a positive SLN, indicating that patients identified as <5% risk by the i31-SLNB test did not have nodal metastases and therefore might not require SLNB. Furthermore, use of i31-SLNB testing could have prevented SLNBs in a total of 35 T1 to T2 tumors, without missing a positive SLN; this correlated to a 32.4-percent decrease in SLNB rates in T1a tumors, a 28.4-percent decrease in T1b tumors, a 12.9-percent reduction in T2a tumors, and a 12.5-percent reduction in T2b tumors.
This study expanded upon initial findings from the DECIDE study, demonstrating the prognostic utility of the i31-SLNB test in clinical SLNB decision-making. Reducing the amount of unnecessary SLNB procedures would benefit both patients and clinicians. Avoiding SLNB in patients with a low risk of SLN positivity would allow them to avoid complications, such as infections and seroma, and healthcare-related costs associated with the procedure. Tumor tissue from the initial biopsy is utilized in 31-GEP testing, meaning that patients do not face additional risks. Additionally, 31-GEP testing for SLNB guidance could potentially lower costs for healthcare payors.
Study limitations included the number of patients with available SLNB results and the lack of a separate prospectively enrolled cohort to compare SLNB procedure rates. Patient preference for or against SLNB was the major factor in SLNB decision-making, which might have introduced variability, but this reflects real-world SLNB decision-making processes.
The study results indicate that the i31-SLNB test effectively identifies patients with cutaneous melanoma with low (<5%) risk of SLN positivity who can safely forgo an SLNB. By combining tumor biology with clinicopathologic factors, the i31-SLNB test can help refine SLNB decision-making, reducing unnecessary procedures while maintaining diagnostic accuracy and ensuring that high-risk patients receive appropriate surgical management.
References
- 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.
- Yamamoto M, Sickle-Santanello B, Beard T, et al. The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study. Curr Med Res Opin. 2023;39(3):417–423.