Early outcome of a 31‐gene expression profile test in 86 AJCC stage IB‐II melanoma patients. A prospective multicentre cohort study

Abstract

Background The clinical and pathological features of primary melanoma are not sufficiently sensitive to accurately predict which patients are at a greater risk of relapse. Recently, a 31‐gene expression profile (DecisionDx‐Melanoma) test has shown promising results. Objectives To evaluate the early prognostic performance of a genetic signature in a multicentre prospectively evaluated cohort. Methods Inclusion of patients with AJCC stages IB and II conducted between April 2015 and December 2016. All patients were followed up prospectively to assess their risk of relapse. Prognostic performance of this test was evaluated individually and later combined with the AJCC staging system. Prognostic accuracy of disease‐free survival was determined using Kaplan–Meier curves and Cox regression analysis. Results of the gene expression profile test were designated as Class 1 (low risk) and Class 2 (high risk). Results Median follow‐up time was 26 months ( IQR 22–30). The gene expression profile test was performed with 86 patients; seven had developed metastasis (8.1%) and all of them were in the Class 2 group, representing 21.2% of this group. Gene expression profile was an independent prognostic factor for relapse as indicated by multivariate Cox regression analysis, adjusted for AJCC stages and age. Conclusions This prospective multicentre cohort study, performed in a Spanish Caucasian cohort, shows that this 31‐gene expression profile test could correctly identify patients at early AJCC stages who are at greater risk of relapse. We believe that gene expression profile in combination with the AJCC staging system could well improve the detection of patients who need intensive surveillance and optimize follow‐up strategies.

Prognostic Gene Expression Profiling in Melanoma: Necessary Steps to Incorporate into Clinical Practice

“…The 31-GEP test further stratified patients with negative SLNB for distant metastatic risk. Similarly, two recent prospective studies (consisting primarily of AJCC stage I/II patients) found GEP class to be the strongest predictor of both local recurrence and distant metastasis [8,9]. Finally, in a study of 1421 prospectively tested T1/T2 tumor stage patients – most undergoing SLNB – from 26 centers, GEP class was a significant predictor of SLNB-positivity [10].…”

Molecular Biomarkers for Melanoma Screening, Diagnosis and Prognosis: Current State and Future Prospects

“…Analytically, this gene expression profile (GEP) has demonstrated reproducibility across instruments in separating "class 1" (low-risk) from "class 2" (high-risk) probability scores and in technical concordance between runs (82). Results from small retrospective and prospective clinical cohorts have suggested improved ability to stratify risk of relapse and distant metastasis independent of SLNB status (83)(84)(85)(86)(87). However, each of these studies are limited by the lack of stage or substage breakdown of test performance, rendering it difficult to determine how much additional information is imparted by the biomarker beyond existing staging criteria.…”

“…However, each of these studies are limited by the lack of stage or substage breakdown of test performance, rendering it difficult to determine how much additional information is imparted by the biomarker beyond existing staging criteria. Podlipnik et al studied the additive utility of DecisionDx probability scores in conjunction with combined AJCC stages ("low-risk": IB-IIA, "high-risk": IIB-IIC) and found disease free survival was lower in melanoma patients with DecisionDx high-risk "class 2" scores, regardless of grouped AJCC staging (87). Furthermore, in a 205 patient cohort, comprised of combined Stage I and II melanoma cases, where the DecisionDx GEP was combined with the AJCC Individualized Melanoma Patient Outcome Prediction Tool, the authors reported improved sensitivity but worse specificity for predicting disease recurrence, distant metastasis, and death compared to either metric alone (78).…”

Integration of a 31-Gene Expression Profile Into Clinical Decision-Making in the Treatment of Cutaneous Melanoma

“…The 31-GEP seeks to identify those T1 and T2 tumors with genetic signatures that are likely to behave in either low-risk or high-risk manners with regard to recurrence, distant metastasis, and mortality. 6,8-11 This test stratified patients into 4 groups: Class 1A (considered low risk of metastasis or recurrence), Classes 1B and 2A (intermediate risk), and Class 2B (high risk). When these groups are further broken down by patient age, it becomes apparent that patients >55 years of age whose tumors are Class 1A have <5% incidence of SLNB positivity.…”