Advancing Melanoma Prognostics: Clinical Evidence Supporting the 31-GEP Test

This video is Part 1 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

Multiple studies (including prospective studies) have demonstrated clinical efficacy for the 31-GEP test in providing consistent and accurate prognostic information for invasive melanoma.

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.

Addressing historical hesitancy around prognostic testing

In this video, Dr Cotter reviews the consensus findings and addresses why prognostic testing has historically been met with some skepticism in dermatology. Unlike diagnosis and treatment, which are central to dermatology training, prognostication has not traditionally played a major role in clinical decision-making for melanoma.

While dermatologists are accustomed to robust clinical trial data guiding therapeutic choices, applying a similar evidence-based framework to prognostic tools has felt less intuitive. Dr Cotter emphasizes that the growing body of data supporting 31-GEP directly addresses these concerns and supports its clinical validity and real-world relevance.

The evidence base supporting 31-GEP

More than 50 peer-reviewed publications have evaluated the 31-GEP test across retrospective studies, cohort analyses, and prospective datasets. Collectively, these studies demonstrate the test’s ability to identify patients at increased risk for sentinel lymph node positivity, recurrence, distant metastasis, and melanoma-specific mortality beyond traditional clinicopathologic factors.

Dr Cotter highlights a pivotal 2023 prospective real-world study that linked outcomes from prospectively tested patients with data from the SEER database. The study confirmed that the test performed in real-world settings as predicted by earlier retrospective trials. Patients with a Class 2B result demonstrated approximately a 7-fold increased risk of death from metastatic melanoma. Importantly, patients who underwent 31-GEP testing also showed a 29% decreased likelihood of dying from melanoma overall.

Updated prospective data and clinical interpretation

Dr Cotter also reviews updated data presented at ASCO 2025, which included additional patients and extended follow-up. The updated analysis confirmed consistent test performance while refining risk estimates. Patients who underwent 31-GEP testing demonstrated a 32% increased likelihood of survival compared with prior estimates of 29%.

Notably, Class 2B patients were shown to have a 4-fold increased risk of death from metastatic melanoma, compared with the previously reported 7-fold risk. Dr Cotter suggests this shift may reflect earlier identification of high-risk patients and more appropriate downstream interventions, including surveillance imaging, sentinel lymph node biopsy, and consideration of adjuvant or neoadjuvant therapy.

What clinical efficacy means for prognostic testing

Clinical efficacy for a prognostic test refers to consistent, reproducible performance that clinicians can rely on when making management decisions. Dr Cotter emphasizes that reproducibility across independent studies is essential for building confidence.

He reviews data demonstrating that traditional AJCC 8 staging alone may fail to adequately risk-stratify certain early-stage patients. In SEER-based analyses, stage IA and IB patients did not always separate cleanly by outcomes. When 31-GEP results were layered onto standard staging, meaningful risk stratification emerged.

Why this matters in clinical practice

Dr Cotter brings the discussion back to day-to-day practice. While Stage I melanoma is associated with approximately 98% melanoma-specific survival, the remaining 2% represent a substantial number of patients nationally. Among the estimated 70,000 to 80,000 Stage I melanoma diagnoses each year in the US, this translates to 1400 to 1600 melanoma-related deaths that are not adequately predicted by standard staging alone.

The 31-GEP test provides additional prognostic information to support decisions around follow-up intensity, referral to surgical or medical oncology, and surveillance imaging. Dr Cotter notes that he now uses the test routinely for all patients with melanoma in his practice because of its impact on clinical decision-making.

Key takeaways

• The 31-GEP test has demonstrated consistent clinical efficacy across retrospective and prospective studies
• Prospective real-world data confirm that 31-GEP performs as predicted outside of clinical trial settings
• Updated ASCO data suggest improved survival among tested patients, possibly reflecting more informed clinical intervention
• The test augments AJCC 8 staging by identifying high-risk patients within early-stage melanoma
• Prognostic insight from 31-GEP can inform surveillance, referral, and treatment discussions in routine practice