Journal of Clinical and Aesthetic Dermatology • Hot Topics in Melanoma November 2025 • EXPERT COMMENTARY

An interview with David Cotter, MD, PhD
Dr. Cotter is with Las Vegas Dermatology in Las Vegas, Nevada.

Dr. Cotter discusses his participation in a consensus panel that focused on the utilization of 31-gene expression profiling (GEP) to help risk stratify patients with cutaneous melanoma, allowing them to achieve the highest level of care.

“The purpose of this expert consensus panel¹ was to offer the practicing dermatologist, dermatology nurse practitioner, and the dermatology physician assistant a best-practice model for the appropriate melanoma patient. This study looked at a systematic review of all articles published on 31-gene expression profiling (GEP). An initial literature search resulted in 150 articles, 26 that met criteria for inclusion to be analyzed by a panel of 10 dermatologists with significant expertise in the management of melanoma. A modified Delphi process was utilized to create nine consensus statements, eight of which received a recommendation with a strength of A and one that received a recommendation with a strength of C.

The reason why we’re doing this is because we need to elevate the care for our patients with melanoma. Every single year in the United States, there are 100,000 cases of invasive cutaneous melanoma that result in approximately 8,000 deaths. Unfortunately, we don’t do a great job identifying which patients are at risk of dying from melanoma. Twenty-five percent of people that ultimately die from this disease are diagnosed as stage I. It’s absolutely unacceptable. These are patients that we would assume, based on population-based estimates, are going to be okay. Furthermore, 35% of patients that ultimately die from metastatic melanoma are stage II. Cumulatively, that results in 6 out of 10 melanoma deaths occurring in patients that are initially diagnosed as stage I and II, and herein lies the problem and, therefore, the reason why we need consensus statements to help guide the management of our patients with cutaneous melanoma.

The first consensus statement is that multiple studies, including prospective studies, have demonstrated clinical efficacy of the 31-GEP test in providing consistent and accurate prognostic information for invasive melanoma. This statement is true, and it’s been validated over and over again in dozens of clinical trials, including multiple prospective studies. When you have a patient with cutaneous melanoma, it’s great to order the 31-GEP test to help risk stratify them.

The next consensus statement is that studies have shown clinical utility of the 31-GEP test for providing prognostic information for invasive melanoma. This one dovetails very nicely off the first statement, and multiple papers have demonstrated this over and over again.

Moving on, studies have shown clinical efficacy for the 31-GEP test in providing prognostic information for invasive melanoma when the thickness or other traditional factors are unknown. This is a very important consensus statement. It’s important to get this information out because one of the utilities of this test is when you have a melanoma that’s been transected. For example, if you do a shave biopsy of a funny brown spot and it comes back at 0.6mm transected, meaning invasive melanoma extends to the base of the biopsy, we don’t know the true Breslow depth of that lesion, and that can lead to confusion and ambiguity over how we manage that patient. Should they go on for additional testing such as a sentinel lymph node biopsy (SLNB)? Do they need to be referred out of our general dermatology clinics? There was a fantastic paper that was done with the lead author, Dr. Whitman, that looks specifically at identifying how the 31-GEP test risk stratifies patients even in transected melanomas. In that study, up to 40 percent of the melanomas were transected, but irrespective of that, the 31-GEP accurately predicted who was going to go on to have a positive node or not. So, we can rely on the 31-GEP test in scenarios where standard staging methods fail us.

This leads into the next statement, integration of the 31-GEP test with traditional staging methods can accurately inform the decision to recommend SLNB. There’s multiple studies that not only demonstrate that we can predict who needs to get it done, but also demonstrate who can avoid it. There’s a series of papers that have shown anywhere from a 20- to 30-percent reduction in the number of unnecessary SLNBs in patients that have a low-risk i31-SLNB score. We’re talking about folks with T1A high-risk or a T1B or even maybe a thin T2A tumor, so anywhere from 0.6 to 1.2mm Breslow depth. In my practice, I find a lot of utility in using the 31-GEP test to avoid an unnecessary SLNB because when the 31-GEP comes back as low risk, meaning less than five-percent risk, those patients in those types of Breslow depth ranges can safely avoid an unnecessary SLNB.

That relates to the next consensus statement. There’s a statistically significant improvement in assessing prognosis when adding 31-GEP results to American Joint Committee on Cancer (AJCC) staging. What we’re talking about here is not 31-GEP versus AJCC, but rather integrating 31-GEP with AJCC; a recent paper looked specifically at gating patients based on their T stage and AJCC stage, and then applying 31-GEP to help refine the patients that go on to have a SLNB, and it did a very good job. We’re talking about a negative predictive value of 100 percent, meaning that we can avoid SLNBs in people who don’t need them without missing anyone who would. Furthermore, when you use the 31-GEP to risk stratify stage I patients, it does a better job than AJCC staging when it comes to melanoma-specific survival (MSS). Stage IA and IB patients in AJCC don’t seem to have a difference in MSS, which is concerning because these are patients that are different stages clinically. However, when we risk stratify them based on the 31-GEP test, we can actually break them apart even from an intrastage standpoint, with Class 2B patients on t

Don’t we have other tools that we can use? Why do we need 31-GEP? Can’t something like an online nomogram do just as well? Well, actually, no. Online nomograms are helpful, but there’s now a series of papers that demonstrate 31-GEP testing is more accurate and precise than online nomograms in predicting the need for SLNB. Furthermore, patients who have had 31-GEP testing have improved MSS and overall survival in comparison to patients who have not received 31-GEP testing. That’s the most poignant of the consensus recommendations, and getting that information out is very important. People need to recognize that when someone with melanoma gets a 31-GEP test, they’re more likely to survive than a matched patient who doesn’t, probably because we are identifying risk and then getting those patients a higher level of care. Maybe they get a SLNB that they wouldn’t have. Maybe they get an imaging test that they wouldn’t have, and they’re likely being followed more closely so that if they do have a recurrence or metastasis, we detect it right away.

This next consensus statement is the only one that didn’t receive a recommendation of A. This one has a C recommendation. This consensus statement is: limited data suggest that patients are more likely than not to be receptive to receiving the data from the 31-GEP test in the discussion about their invasive melanoma and management. A “C” here is not because it’s not a good idea to use the test. It’s because when we grade the evidence, it’s based on the combination of types of papers that are out there. Prospective clinical trials receive the highest level of strength in our evidence analysis, followed by systematic reviews, network meta-analyses, and then as we get farther away from those more robust clinical studies, we have a lower quality of evidence. The types of papers that support the role of how patients will be receptive for 31-GEP testing haven’t been done in a prospective manner, the way that some of these other consensus statements have. I still think it’s a good idea, and in my practice, patients do like having more information. I’ve never had someone say, “No, I don’t want to know what’s going on with my melanoma.”

That brings us to the last consensus statement. The existing data strongly support the utilization of 31-GEP testing as a best practice for the appropriate melanoma patient. I like that term best practice, because that’s what we’re aiming for. We’re aiming to augment the level of care we offer our patients, and we can utilize 31-GEP testing to do exactly that.

¹. Burshstein J, Cockerell C, Cotter D, et al. 31-gene expression profiling for cutaneous melanoma: an expert consensus panel. Derm Online J. 2025. In Press.

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