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Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous MelanomaA Systematic Review and Meta-analysis

Educational Objective
To examine the performance of commercially available gene expression profile (GEP) tests.
1 Credit CME
Key Points

Question  What is the performance of commercially available gene expression profile tests in predicting cutaneous melanoma outcomes in patients with stage I or stage II melanoma?

Findings  In this systematic review and meta-analysis of 7 studies including 1450 participants, gene expression profile test performance varied significantly by disease stage in external validation studies and was better at identifying recurrence in patients with stage II disease than in those with stage I disease. Studies were rated as having moderate to high risk of bias, and the quality of evidence was assessed as low to very low.

Meaning  In patients with clinically localized melanoma, there was variation in gene expression profile test performance by disease stage, suggesting limited potential for clinical utility for patients with stage I melanoma.


Importance  The 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.

Results  In 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 Relevance  The 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.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: May 10, 2020.

Corresponding Author: Michael A. Marchetti, MD, Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th St, New York, NY 10021 (marchetm@mskcc.org).

Published Online: July 29, 2020. doi:10.1001/jamadermatol.2020.1731

Author Contributions: Drs Marchetti and Bartlett contributed equally. Drs Marchetti and Bartlett had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Marchetti, Coit, Yu, Mancebo, Bartlett.

Acquisition, analysis, or interpretation of data: Marchetti, Dusza, Yu, McLean, Hu, Nanda, Matsoukas, Bartlett.

Drafting of the manuscript: Marchetti, Coit, Dusza, Yu, McLean, Bartlett.

Critical revision of the manuscript for important intellectual content: Marchetti, Dusza, Hu, Nanda, Matsoukas, Mancebo, Bartlett.

Statistical analysis: Marchetti, Dusza, McLean.

Administrative, technical, or material support: Marchetti, Coit, McLean, Hu, Matsoukas.

Supervision: Marchetti, Coit, Bartlett.

Conflict of Interest Disclosures: Dr Marchetti reported being a member of the Melanoma Prevention Working Group, which has drafted a consensus statement on the use of gene expression profile tests in cutaneous melanoma. No other disclosures were reported.

Funding/Support: This research was funded in part through the Memorial Sloan Kettering Cancer Center institutional National Institutes of Health/National Cancer Center Support Grant P30 CA008748 (Drs Marchetti, Coit, Dusza, Hu, and Bartlett and Mss Yu, Mclean, Nanda, and Matsoukas).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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