From 31-GEP Risk Stratification to Melanoma Outcomes

This video is Part 4 of a 4-part expert series designed to strengthen clinician confidence in the use of the 31-gene expression profiling (31-GEP) test for prognostic assessment in cutaneous melanoma. Across the series, David Cotter, MD, PhD, addresses common questions and hesitations around molecular prognostic testing to support more consistent and effective integration of 31-GEP into routine dermatologic practice.

Expert consensus statement

Patients who have received 31-GEP testing have improved melanoma-specific survival (MSS) and overall survival (OS) in comparison to patients who have not received 31-GEP testing.

This consensus statement comes from the expert panel publication “31-Gene Expression Profiling for Cutaneous Melanoma: An Expert Consensus Panel” and serves as the foundation for this discussion.

Can a prognostic test improve outcomes?

The concept that a prognostic test could contribute to improved survival may initially seem surprising. Unlike a medication, surgical intervention, or imaging modality, 31-GEP testing does not directly treat melanoma. Instead, it provides additional prognostic information that may inform subsequent clinical decisions.

Dr Cotter explains that this distinction is central to understanding the survival data. By identifying patients at higher risk of poor outcomes, 31-GEP testing may prompt clinicians to intensify follow-up or pursue additional interventions. Conversely, identifying patients at lower risk may help clinicians avoid procedures or surveillance that are unlikely to provide sufficient benefit.

This raises what Dr Cotter describes as a key clinical question: Does testing actually change patient outcomes?

Real-world survival data

Dr Cotter highlights real-world data generated through collaboration with the National Cancer Institute using the Surveillance, Epidemiology, and End Results (SEER) database. The analysis matched patients who underwent 31-GEP testing with patients who did not, accounting for factors including T stage, age, Breslow depth, and socioeconomic status.

In the initial analysis, patients with a class 2B 31-GEP result were nearly 7 times more likely to die from melanoma than those with a class 1A result. This comparison, among patients who underwent testing, demonstrates the ability of 31-GEP to further stratify melanoma-specific risk.

The investigators then examined a different question: whether outcomes differed between patients who received 31-GEP testing and those who did not. After matching the groups for factors including T stage, age, Breslow depth, and socioeconomic status, patients who underwent 31-GEP testing had a hazard ratio for melanoma-specific death of 0.71, corresponding to a 29% lower risk compared with untested patients.

Dr Cotter also discusses an updated 2025 analysis incorporating additional patients and follow-up. In the updated data, class 2B patients had approximately 4 times the risk of melanoma-specific death compared with class 1A patients, while the hazard ratio for melanoma-specific death among 31-GEP–tested patients compared with untested patients was 0.68, corresponding to a 32% lower risk.

Dr Cotter notes that the change in risk estimates between analyses could reflect greater statistical refinement as additional patients and events accrue. He also raises another possibility: Clinical management may be changing as evidence supporting risk-directed melanoma care continues to accumulate. Advances in adjuvant therapy, greater familiarity with 31-GEP testing, and increased use of surveillance strategies among patients identified as high risk may all contribute to the outcomes observed in contemporary practice.

From risk stratification to clinical action

For prognostic information to affect outcomes, it must ultimately inform what happens next. Dr Cotter points to clinical utility data examining surveillance imaging among patients at increased risk.

In a study of more than 600 patients, investigators evaluated routine surveillance with CT and brain MRI, performed approximately every 6 months, to identify recurrence before patients became symptomatic. Among high-risk patients identified through GEP testing, routine imaging was associated with earlier detection of metastases and lower tumor burden when checkpoint inhibitor therapy was initiated.

Survival also differed between groups: 76.3% of GEP-tested patients undergoing routine imaging were alive at the end of the study compared with 50% of patients who underwent imaging reactively after recurrence became clinically apparent.

These findings illustrate the potential downstream value of more precise risk stratification. Identifying patients at increased risk may allow clinicians to intensify surveillance and detect metastatic disease at an earlier, potentially more manageable point in its course.

Refining sentinel lymph node biopsy decisions

Risk stratification may also help inform decisions surrounding sentinel lymph node biopsy (SLNB). Population-level estimates can leave uncertainty about which patients with thinner melanomas are most likely to benefit from the procedure.

Dr Cotter notes that across melanomas measuring less than 1 mm, the population-level likelihood of a positive sentinel lymph node is approximately 5.3%. This creates a difficult balance: Routinely performing SLNB in this population exposes many patients with node-negative disease to an invasive procedure and its associated costs, while not performing SLNB may miss the smaller subset with occult nodal disease.

31-GEP testing may provide another layer of individualized risk information to help refine these decisions. For some patients with thin melanoma, a higher-risk result may support consideration of SLNB despite otherwise reassuring clinicopathologic features. Conversely, among selected patients with T1b or T2a tumors, a low-risk molecular profile may identify patients for whom SLNB could potentially be avoided. Dr Cotter notes that available data suggest this approach could reduce unnecessary SLNB procedures in approximately 25% to 30% of these patients.

Translating prognostic information into daily practice

The clinical value of prognostic testing extends beyond assigning a patient to a risk category. More precise risk stratification may allow clinicians to align follow-up, surveillance, and procedural decisions more closely with an individual patient’s risk.

For lower-risk patients, this may mean avoiding interventions such as SLNB or intensive surveillance when they are unlikely to provide meaningful benefit. For higher-risk patients who might not otherwise be identified through conventional clinicopathologic factors alone, 31-GEP results may support closer surveillance, additional staging procedures, or other risk-appropriate management.

Dr Cotter emphasizes that the association between 31-GEP testing and improved real-world outcomes provides an important perspective on the role of prognostic testing. The test itself does not alter the course of melanoma; rather, the information it provides may enable clinicians to make different decisions about what happens next.

Ultimately, he frames the value of 31-GEP testing as getting the right intervention to the right patient at the right time, using individualized prognostic information to guide clinical action.