The 31-Gene Expression Profile Test Identifies Patients with AJCC T1a (<0.8mm) Cutaneous Melanoma at Increased Risk of 5-year Melanoma-Specific Mortality

T1a cutaneous melanoma accounts for 75% of newly diagnosed tumors, with high associated survival rates (over 97% 5-year survival rates). However, a proportion of patients with T1a tumors do experience tumor recurrence and die from their disease. It is critically important, therefore, to identify the high-risk patients within this population considered low risk based on clinical or pathological features alone, as these high-risk patients would be expected to benefit from more extensive management (e.g., surveillance imaging, more frequent follow-up) and, thus, improve outcomes. The 31-gene expression profile (GEP) test stratifies risk of sentinel lymph node positivity, recurrence, metastasis, and death. Incorporating 31-GEP molecular tumor risk information with clinical and pathological staging factors can identify patients with a high risk of poor outcomes who may benefit from escalated clinical management to improve patient outcomes. We analyzed patients with T1a tumor clinically tested with the 31-GEP who were diagnosed between 2013–2019 linked to the SEER registry database and who had at least 5 years of follow up or died from their disease (n=750). Kaplan-Meier analysis was used to estimate 5-year melanoma-specific survival (MSS) rates, and differences between groups were compared using the log-rank test. Univariate analyses were conducted to identify predictors of melanoma-specific mortality. Among patients with T1a tumors, 88 out of 750 (11.7%) had non-Class 1A 31-GEP results. Patients with Class 2B or Class 1B/2A results had lower 5-year MSS than those with Class 1A results (86.2%, 88.1%, vs. 97.1%; p<0.001). Patients with Class 2B results had 5-year MSS rates comparable to those in T2b tumors (82.4%) or stage IIA CM (85.1%) from the same SEER database. A 31-GEP Class 2B (HR=3.30 [95% CI: 1.12-9.76]) and Class 1B/2A result (HR=2.04 [95% CI: 0.75-5.51]) were significant predictors of melanoma-specific mortality in multivariate analyses with age and AJCC stage. These data emphasize the importance of identifying patients with T1a tumors and non-Class 1A results for informed management decisions. We have demonstrated that not only are non-Class 1A results possible in T1a tumors, but also that non-Class 1A patients have higher mortality. Thus, the 31-GEP result can have a significant impact on understanding a patient’s prognosis, helping to guide more informed, risk-aligned care.