Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous Melanoma

Abstract

IMPORTANCEThe performance of prognostic gene expression profile (GEP) tests for cutaneous melanoma is poorly characterized. OBJECTIVE To systematically assess the performance of commercially available GEP tests in patients with American Joint Committee on Cancer (AJCC) stage I or stage II disease.DATA SOURCES For this systematic review and meta-analysis, comprehensive searches of PubMed/MEDLINE, Embase, and Web of Science were conducted on December 12, 2019, for English-language studies of humans without date restrictions.STUDY SELECTION Two reviewers identified GEP external validation studies of patients with localized melanoma. After exclusion criteria were applied, 7 studies (8%; 5 assessing DecisionDx-Melanoma and 2 assessing MelaGenix) were included.DATA EXTRACTION AND SYNTHESIS Data were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation.MAIN OUTCOMES AND MEASURES Proportion of patients with or without melanoma recurrence correctly classified by the GEP test as being at high or low risk. RESULTSIn the 7 included studies, a total of 1450 study participants contributed data (age and sex unknown). The performance of both GEP tests varied by AJCC stage. Of patients tested with DecisionDx-Melanoma, 623 had stage I disease (6 true-positive [TP], 15 false-negative, 61 false-positive, and 541 true-negative [TN] results) and 212 had stage II disease (59 TP, 13 FN, 78 FP, and 62 TN results). Among patients with recurrence, DecisionDx-Melanoma correctly classified 29% with stage I disease and 82% with stage II disease. Among patients without recurrence, the test correctly classified 90% with stage I disease and 44% with stage II disease. Of patients tested with MelaGenix, 88 had stage I disease (7 TP, 15 FN, 15 FP, and 51 TN results) and 245 had stage II disease (59 TP, 19 FN, 95 FP, and 72 TN results). Among patients with recurrence, MelaGenix correctly classified 32% with stage I disease and 76% with stage II disease. Among patients without recurrence, the test correctly classified 77% with stage I disease and 43% with stage II disease. CONCLUSIONS AND RELEVANCEThe prognostic ability of GEP tests among patients with localized melanoma varied by AJCC stage and appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021

“…The use of prognostic gene expression profiling (GEP) tests (before or after SLNB) requires further investigation across large, prospectivelyenrolled cohorts of unselected patients. Given the low probability of metastasis in stage I melanoma and a higher proportion of false-positive results, [151][152][153][154] the NCCN panel concluded that currently available GEP tests should not replace pathologic staging procedures, be used to determine SLNB eligibility, or guide clinical-decision making in this subset of patients (see ME-2A, footnote d, and ME-F 1 of 3; available in these guidelines at NCCN.org). Principles of nuclear medicine, surgery, and pathology pertaining to SLNB have also been recently revised (ME-F 2 and 3; available in these guidelines at NCCN.org).…”

Bioinformatic and Machine Learning Applications in Melanoma Risk Assessment and Prognosis: A Literature Review

“…Similarly, Gastman et al found that 31-GEP accurately identified high-risk patients who are likely to recur or die of melanoma in low-risk subgroups (e.g., sentinel lymph node-negative disease, stage I and IIA) [32]. A meta-analysis reported that 31-GEP performance varied, and was a better predictor of recurrence in stage II disease than in stage I [33]. However, a separate study suggested that there is limited cost-benefit of 31-GEP utilization in stage IIIA melanoma due to the limited survival benefit of this tool for this patient subgroup [34].…”

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

“…To determine the impact of these GEPs, and other tests, on decision to biopsy SLNs and their role in staging (see below), a large retrospective study and/or longitudinal studies will be necessary to determine how these biomarkers predict clinically meaningful outcomes like distant metastasis freesurvival and all-cause mortality. Meta-analysis of existing studies has demonstrated that currently available GEP tests have limited ability to prognosticate recurrence in early stage melanomas (96). Due to the cost of conducting such trials, in terms of economic considerations and irreplaceable patient samples, the melanoma community will need to identify and prioritize the coordinated validation of only the most promising biomarker assays.…”