The 31-Gene Expression Profile Test Outperforms AJCC in Stratifying Risk of Recurrence in Patients with Stage I Cutaneous Melanoma

Abstract

Background: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. Methods: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, “combined”). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013–2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. Results: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)—better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). Conclusions: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans.