QHow do you assess melanoma prognosis when sentinel lymph node biopsy (SLNB) results are negative?

Melanoma patients with a Breslow depth greater than 0.8 mm are eligible for a sentinel lymph node biopsy (SLNB). The SLNB procedure provides strong prognostic information regarding a patient’s risk for recurrence and mortality from melanoma. A positive node changes the overall AJCC staging for a patient. However, 88% of patients who receive an SLNB will have a negative result. So, what should physicians turn to for melanoma prognosis when the patient has a negative SLNB?

If you look at AJCC 5-year survival curves, patients with stage IIA and stage IIIA have similar 5-year survival outcomes. Current guidelines do not provide clear guidance for surveillance in Stage IB and IIA patients. The 31-GEP test for melanoma was developed to provide additional prognostic information that can be added to staging.

In a recent paper by Bailey et al., over 4,000 patients were prospectively tested and pulled from the SEER database. This paper aimed to establish the clinical validity of the 31-GEP class result. In a multivariate analysis, the following covariates were independent predictors of melanoma-specific survival (MSS): 31-GEP class 1B/2A, 31-GEP Class 2B, age, Breslow thickness, and positive SLNB. This paper demonstrates that a positive lymph node is a strong prognostic factor, but so is the 31-GEP result. Two-thirds of the patients who died in the landmark MSLT-1 trial were SLNB negative. There is a need for additional prognosis when a patient has a negative node, and this is where the 31-GEP test comes in.

The 31-GEP result, an independent prognostic factor, now provides patient-specific risk estimates. Based on a validated algorithm published by Jarell et al., the 31-GEP continuous score is integrated into an algorithm that gives clinicians patient-specific estimates for recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and MSS. These estimates become increasingly important in stage IB and IIA patients with a negative node because they do not qualify for drug therapy. In a recent poster from a prospective validation study, the 31-GEP test was able to separate risk in patients who are stage IB/IIA. Patients with an elevated 31-GEP score can be followed with closer surveillance, including imaging, while patients with a low-risk 31-GEP score can be safely followed by medical dermatologists since the risk of recurrence is relatively low.

References:

1. Society of Surgical Oncology. Clinical Recommendations. Society of Surgical Oncology website. https://surgonc.org/resources/clinical-recommendations/. Published 2024. Accessed March 12, 2025.
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4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 2.2025. National Comprehensive Cancer Network website. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1492. Published 2025. Accessed March 12, 2025.
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7. Jarell AD, Bailey CN, Martin BJ, Prieto P. The integrated 31-gene expression profile (i31-GEP) test for cutaneous melanoma outperforms a clinicopathologic-only nomogram at identifying patients who can safely forego sentinel lymph node biopsy. J Am Acad Dermatol. 2022;87(6):1234-1242. doi:10.1016/j.jaad.2022.08.015.
8. Dhillon S, Duarte-Bateman D, Fowler G, et al. Routine imaging guided by a 31-gene expression profile assay results in earlier detection of melanoma with decreased metastatic tumor burden compared to patients without surveillance imaging studies. Arch Dermatol Res. 2023;315(12):2295-2302. doi:10.1007/s00403-023-02613-6.