Using GEP Results to Guide SLNB and Imaging in Stage I-II Melanoma

In this episode of Expert Perspectives "Using GEP Results to Guide SLNB and Imaging in Stage I-II Melanoma," Dr. Singh turns to the practical question of where GEP testing changes care in his own practice.

Dr. Singh says he finds GEP testing most helpful in patients with stage I and stage II melanoma. Many stage I patients are not eligible for sentinel lymph node biopsy. Others decline the procedure for reasons that include fear of surgery. When a stage I patient returns a high-risk GEP result, he will likely offer a sentinel lymph node biopsy that otherwise would not be performed. He acknowledges this may surprise some clinicians, but reminds them that about a quarter of melanoma deaths occur in early-stage disease.

Stage II patients with a negative node biopsy concern him even more. He notes this group accounts for about two-thirds of US melanoma deaths. When these patients have a Class 2A or Class 2B GEP result, he will likely pursue additional imaging. Imaging often detects disease before it becomes clinically evident, and patients whose spread is caught earlier tend to fare significantly better. He cites data showing that about 25% of Class 2 patients eventually develop metastasis, a signal strong enough to warrant closer follow-up.

Dr. Singh then discusses prospective evidence on the integrated 31-GEP algorithm. He describes a 2025 paper by Dr. Guenther and colleagues showing the 31-GEP score was the most accurate predictor of nodal melanoma. In T1 and T2 tumors, it was independently the strongest predictor of metastasis. The score correlated more closely with outcomes than Breslow depth or ulceration. For thin melanomas, he calls the i31-GEP test critical because it uncovers bad actors hiding within a seemingly favorable cohort. He describes these tumors as a wolf in sheep's clothing, and says finding them can significantly improve survival.

In "Interpreting GEP Results in Melanoma: Limitations and Patient-Centered Care," Dr. Singh will address when GEP testing adds little value and how to keep results in proportion to each patient's goals and health.