The i31-SLNB Identifies Patients with Cutaneous Melanoma Who Have Less than 5% Risk of SLN Positivity while the CP-GEP does not

Introduction: Sentinel lymph node biopsy (SLNB) is a prognostic procedure that can help guide surveillance and treatment management plans for patients with cutaneous melanoma. However, up to 88% of SLNBs are negative, suggesting that most patients may not require SLNB. The National Comprehensive Cancer Network guidelines recommend that patients with <5% risk of SLN positivity should avoid SLNB, whereas those with a risk of 5-10% should be considered for SLNB, and those with a risk of >10% should be offered SLNB. This study compared the performance of two gene expression profile (GEP) tests designed to identify patients with low risk (<5% risk) of SLN positivity: the i31-SLNB and CP-GEP. Methods: SLN false-negative rates were analyzed for the i31-SLNB using data from Whitman et al. (JCO PO 2021; T1-T4: n=1,258) and for the CP-GEP using publicly available data from Sondak et al. (Society for Melanoma Research 2024; T1-T3: n=1,686). Only patients who had an SLNB were included in the analysis. False negative rate (FNR) is calculated as 1-NPV. Results: The i31-SLNB had an FNR = 3.9% in patients classified as low risk (n=233) which is below the 5% guideline cut point for avoiding an SLNB. The CP-GEP had an FNR = 7.1% in patients classified as low risk (n=624) which is above the 5% guideline cut point for avoiding an SLNB. Comparing FNRs in T1b tumors showed that the i31-SLNB had an FNR = 2.8% compared with 5.1% for the CP-GEP. Similar results were seen among T2a tumors, with the i31-SLNB having an FNR = 4.3% compared with an FNR = 7.3% for the CP-GEP. Conclusions: The i31-SLNB accurately identifies patients with a risk of SLN positivity below the NCCN guideline of 5% risk threshold for avoiding SLNB, with a false-negative rate nearly 50% lower than that of CP-GEP. Conversely, patients identified as low risk by CP-GEP had SLN positivity rates over 5%, suggesting it is not sufficient for informing clinical decisions regarding SLNB.