Refining Melanoma Prognosis Beyond AJCC8 Staging

This video is Part 3 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

There is a statistically significant improvement in assessing prognosis when adding 31-GEP results to AJCC8 staging.

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.

AJCC8 provides the foundation, but not the complete picture

Dr Cotter emphasizes that AJCC8 remains the cornerstone of melanoma staging, providing a standardized framework for estimating prognosis and guiding management. However, like any population-based staging system, it cannot fully capture the biological variability among individual tumors.

He argues that meaningful gaps remain in traditional risk assessment. Although stage I melanoma is generally associated with an excellent prognosis, a small subset of patients will still progress to metastatic disease. Likewise, patients initially diagnosed with stage I or II melanoma ultimately account for the majority of melanoma-related deaths in the United States, demonstrating the need for tools that can identify higher-risk individuals earlier in the disease course.

Dr Cotter also highlights data suggesting that conventional staging alone may not adequately distinguish outcomes within early-stage disease, reinforcing the limitations of relying exclusively on AJCC8 for prognostic assessment.

Refining prognosis by incorporating tumor biology

According to Dr Cotter, adding 31-GEP testing to AJCC8 staging allows clinicians to better distinguish patients with favorable versus unfavorable tumor biology within the same clinical stage.

He reviews studies showing that 31-GEP refines risk within each AJCC8 stage. Across stage I, II, and III disease, patients with Class 1A results consistently demonstrate better melanoma-specific survival than stage-matched patients with Class 2B results. These findings suggest that molecular profiling can identify biologically aggressive tumors that are not fully distinguished by clinicopathologic staging alone.

Using prognostic information to individualize management

For Dr Cotter, improved prognostic discrimination translates into more personalized clinical decision-making.

He explains that 31-GEP results influence several aspects of patient management, including follow-up intensity, surveillance strategies, and referral patterns. For example, a patient with a relatively thin melanoma who would not traditionally be considered for sentinel lymph node biopsy (SLNB) may warrant referral to surgical oncology if a high-risk molecular profile suggests greater metastatic potential.

Similarly, patients with negative SLNB results but high-risk 31-GEP findings may still benefit from referral to medical oncology for consideration of additional surveillance or systemic treatment discussions. Dr Cotter emphasizes that node-negative status does not eliminate metastatic risk and believes molecular prognostic information can help identify patients who may require closer monitoring despite otherwise reassuring staging.

Surveillance imaging in molecularly high-risk patients

Dr Cotter also reviews evidence supporting surveillance imaging for patients identified as high risk by 31-GEP testing.

He discusses a multicenter study of SLNB-negative patients in which individuals with elevated-risk 31-GEP results underwent scheduled surveillance imaging, while a matched comparison group received imaging only after symptoms developed. Routine imaging identified metastatic disease substantially earlier, with patients presenting with lower tumor burden at the time of detection than those undergoing reactive imaging.

He notes that earlier detection was also associated with improved survival at follow-up, supporting the concept that identifying metastases while patients remain asymptomatic may create opportunities for earlier therapeutic intervention.

For Dr Cotter, these findings illustrate how molecular risk stratification may help identify patients who could benefit from surveillance strategies beyond those typically recommended based on AJCC8 staging alone.

Integrating AJCC8 and 31-GEP into clinical practice

In closing, Dr Cotter describes AJCC8 as the essential framework for melanoma staging, while viewing 31-GEP testing as an additional layer of prognostic refinement that individualizes risk assessment.

Rather than replacing traditional staging, he believes combining clinicopathologic information with molecular profiling provides a more complete understanding of each patient's risk. This integrated approach can help guide decisions regarding referral for SLNB, surveillance imaging, follow-up intensity, and multidisciplinary management, allowing clinicians to tailor care according to both stage and tumor biology.