A Systematic Review and Meta-Analysis of Gene Expression Profiling for Primary Cutaneous Melanoma Prognosis

Abstract

To decrease morbidity and mortality from melanoma, it is imperative to identify patients who are at high risk for developing widespread disease. Gene expression profiling (GEP) technology may impact melanoma management as physicians are better equipped to measure prognosis. Many different GEP signatures have been investigated. We searched Pubmed, Cochrane CENTRAL, and Embase for studies on GEP in primary melanoma prognosis and assessed GEP signatures for prognostic and analytic validity and clinical impact. The relationship between GEP and survival was measured using hazard ratios (HR) and odds ratios (OR). We found twenty-nine articles comprising 9 gene signatures meeting inclusion criteria and conducted a meta-analysis on 6 studies on a 31-gene signature. High-risk GEP status was associated with poorer recurrence-free survival (HR=7.22; 95% CI, 4.75-10.98), distant metastasis-free survival (HR=6.62; 95% CI, 4.91-8.91), and overall survival (HR=7.06; 95% CI, 4.44-11.22); as well as sentinel lymph node biopsy positivity (OR=2.99; 95% CI, 2.15-4.15). With recent improvements in treating advanced melanoma, accurately assessing prognosis is important. This study has clinical implications for melanoma patients who may benefit from prognostic testing. These results may be useful to clinicians when ordering GEP testing and help them make better management decisions.

Integrating the Melanoma 31-Gene Expression Profile Test with Surgical Oncology Practice Within National Guideline and Staging Recommendations

“…Evaluation of these end points was limited by the relatively short follow-up of this cohort. However, the clinical accuracy of the 31-GEP test to predict patient outcomes has been extensively reported, including two recent systematic reviews and meta-analyses [23,24,34,37,38], including in prospective cohorts [26,27]. Longer follow-up of our cohort will permit an evaluation of the combination of the test result and completed management plans to identify recurrence.…”

Distant metastases from an originally diagnosed melanoma in situ primary tumor

“…Increased screening, review of systems, and check‐ins may detect non‐dermatologic metastases, as seen in our patient with weakness. Sentinel lymph node biopsy, follow‐up focused on recurrence, and gene‐expression profiling could be useful 4,5 . Dermatologists should counsel elderly patients with head and neck stage IA melanomas that there is a real chance of metastases.…”

Integrating 31-Gene Expression Profiling With Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction

“… 21 - 23 The 31-GEP Class is an independent predictor of recurrence, including nodal recurrence, as demonstrated in meta-analyses and multiple prospective and retrospective studies. 23 - 29 Vetto et al 24 showed that patients with T1-T2 tumors, 55 years and older, and a 31-GEP Class 1A result have < 5% risk of SLN positivity and maintain > 99% melanoma-specific survival. However, to develop a more individualized SLN positivity risk assessment for each patient, we used advanced artificial intelligence techniques to integrate the continuous 31-GEP score with individual patient tumor CP features.…”

“…[21][22][23] The 31-GEP Class is an independent predictor of recurrence, including nodal recurrence, as demonstrated in metaanalyses and multiple prospective and retrospective studies. [23][24][25][26][27][28][29] Vetto et al 24 showed that patients with T1-T2 tumors, 55 years and older, and a 31-GEP Class 1A result have , 5% risk of SLN positivity and maintain . 99% melanoma-specific survival.…”