Expert Consensus on the Use of Prognostic Gene Expression Profiling Tests for the Management of Cutaneous Melanoma: Consensus from the Skin Cancer Prevention Working Group

Abstract

Background: Prognostic assessment of cutaneous melanoma relies on historical, clinicopathological, and phenotypic risk factors according to American Joint Committee on Cancer(AJCC) and National Comprehensive Cancer Network (NCCN) guidelines but may not account for a patient's individual additional genetic risk factors. Objective: To review the available literature regarding commercially available gene expression profile (GEP) tests and their use in the management of cutaneous melanoma. Methods: A literature search was conducted for original, English-language studies or metaanalyses published between 2010 and 2021 on commercially available GEP tests in cutaneous melanoma prognosis, clinical decision-making regarding sentinel lymph node biopsy, and realworld efficacy. After the literature review, the Skin Cancer Prevention Working Group, an expert panel of dermatologists with specialized training in melanoma and non-melanoma skin cancer diagnosis and management, utilized a modified Delphi technique to develop consensus statements regarding prognostic gene expression profile tests. Statements were only adopted with a supermajority vote of [ 80%. Results: The initial search identified 1064 studies/meta-analyses that met the search criteria. Of these, we included 21 original articles and meta-analyses that studied the 31-GEP test (DecisionDx-Melanoma; Castle Biosciences, Inc.), five original articles that studied the 11-GEP test (Melagenix; NeraCare GmbH), and four original articles that studied the 8-GEP test with clinicopathological factors (Merlin; 8-GEP ? CP; SkylineDx B.V.

Incorporating Prognostic Gene Expression Profile Assays into the Management of Cutaneous Melanoma: An Expert Consensus Panel

“…The 31-GEP test is a CM prognostic assay that measures the level of expression of 28 target genes and three control genes in order to stratify CM into low-risk (class 1A), intermediate risk (class 1B/2A), and high-risk (class 2B) categories based on risk of recurrence, metastasis and probability of sentinel lymph node biopsy (SLNB) positivity. 3 The test utilizes RNA from formalin-fixed, paraffin-embedded (FFPE) tissue samples of the primary lesion and identifies the level of expression of the 31 genes using qRT-PCR. 3 The test also adds clinical and histologic data into the GEP values to provide an integrated prognostic assessment (i31-GEP test).…”

“…3 The test utilizes RNA from formalin-fixed, paraffin-embedded (FFPE) tissue samples of the primary lesion and identifies the level of expression of the 31 genes using qRT-PCR. 3 The test also adds clinical and histologic data into the GEP values to provide an integrated prognostic assessment (i31-GEP test).…”

“…2 The development and validation of gene expression profile (GEP) assays that use a quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to identify the level of expression of certain groups of signature genes has significantly advanced cancer prognostic assessment. [3][4][5][6][7][8] Because the level of expression of these signature genes varies between benign and malignant lesions as well as lesions that have a lower or higher likelihood for metastasis, these tests can provide important prognostic information. In addition, studies have demonstrated that genomics can identify a high-risk subset of CM patients with stage I and II disease that are at greater risk for recurrence, metastasis, and increased mortality based on their lesions' genetic profile.…”

“…In addition, studies have demonstrated that genomics can identify a high-risk subset of CM patients with stage I and II disease that are at greater risk for recurrence, metastasis, and increased mortality based on their lesions' genetic profile. [3][4][5] Tens of thousands of CM GEP tests are currently being ordered annually in the US to aid clinicians in their prognostic assessment of patients with CM. 9 However, current CM staging according to AJCC8 as well as guidelines put forth by the National Comprehensive Cancer Network (NCCN) do not formally incorporate GEP test data to further stratify patients.…”

Expression profile and prognostic values of LSM family in skin cutaneous melanoma

“…Despite the development of surgical and systemic therapies [7], the survival rate of patients with SKCM remains relatively low. In terms of precision medicine, various studies have revealed that differentially expressed genes (DEGs) could be helpful in clarifying the tumor molecular biology, prognosis, and molecular targeted drugs in SKCM [8,9]. To date, a large number of biomarkers have been discovered [10][11][12], but most are in the basic research stage, and there are only a few biomarkers that can be used to guide clinical practice.…”