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Meta-Analysis
. 2020 Sep 1;156(9):953-962.
doi: 10.1001/jamadermatol.2020.1731.

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

Michael A Marchetti  1   2 , Daniel G Coit  3 , Stephen W Dusza  1 , Ashley Yu  1 , LaToya McLean  3 , Yinin Hu  3 , Japbani K Nanda  1 , Konstantina Matsoukas  4 , Silvia E Mancebo  2   5 , Edmund K Bartlett  3
Affiliations
Meta-Analysis

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

Michael A Marchetti et al. JAMA Dermatol. .

Abstract

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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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.. Estimated Proportion (EP) of Patients With a Melanoma Recurrence Correctly Classified as High Risk by DecisionDx-Melanoma, Stratified by American Joint Committee on Cancer Stage
The study by Podlipnik et al was excluded from stage I analysis because there were no melanoma recurrences. FN indicates false-negative results; TP, true-positive results.
Figure 2.
Figure 2.. Estimated Proportion (EP) of Patients Without a Melanoma Recurrence Correctly Classified as Low Risk by DecisionDx-Melanoma, Stratified by American Joint Committee on Cancer Stage
FP indicates false-positive results; TN, true-negative results.
See this image and copyright information in PMC

Comment in

References

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