Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Cutaneous melanoma
Treatment: DecisionDx-Melanoma assay
The DecisionDx-Melanoma assay was not medically necessary.

The NCCN Guidelines for Melanoma version 2.2019 (https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf) do not recommend DecisionDx-Melanoma in the work up of any stage of cutaneous melanoma. Per the guidelines, "While there is interest in newer prognostic molecular techniques such as gene expression profiling to differentiate benign from malignant neoplasms, or melanomas at low- versus high-risk for metastasis, routine (baseline) genetic testing of primary cutaneous melanomas (before or following SLNB) is not recommended outside of a clinical study (trial)." Gene expression profile signature (DecisionDx-Melanoma) to predict visceral metastatic risk in patients with stage I and stage II cutaneous melanoma is currently not standard of care in the management of cutaneous melanoma and is therefore not considered medically necessary. 

The DecisionDx-Melanoma test (Castle Bioscience, Inc., Friendswood, TX) is a multigene expression assay designed to predict metastasis in individuals with stage I or stage II cutaneous melanoma who have no sign of disease beyond the original tumor. The laboratory test is a signature of 31 genes, 28 discriminating genes and three control genes, that classifies tumors as class-1 (low risk of metastasis) or class-2 (high risk of metastasis), using reverse transcription polymerase chain reaction (RT-PCR) on formalin-fixed paraffin-embedded (FFPE) primary tumor tissue specimens obtained from either biopsy or excision of the cutaneous melanoma. There is wide variability in metastatic rates within and across tumor-node-metastasis (TNM) stage groupings in individuals with cutaneous melanoma. 

The DecisionDx-Melanoma test is purported to predict the risk of tumor metastasis in confirmed melanoma independent of currently used metrics of risk assessment such as Breslow thickness, ulceration status (present or absent), dermal mitotic rate, microsatellitosis (present or absent), American Joint Committee on Cancer (AJCC) stage, and sentinel lymph node biopsy status. It is suggested this information would add to a comprehensive baseline evaluation and determination of the initial surveillance and treatment of an individual with high-risk stage I or II disease. 

The clinical validity of the DecisionDx-Melanoma test was evaluated in a prospective, multicenter study of class-1 cutaneous melanoma tumors which analyzed microarray expression data to identify a prognostic 28-gene signature to predict risk of metastasis (Gerami, 2015). Based on modeling analysis of cohorts of primary cutaneous melanoma tumor tissue and Kaplan-Meier analysis, the study reported the five-year disease-free survival (DFS) rates in the development set were 100% and 38% for predicted classes-1 and -2 tumors, respectively (p<0.0001). DFS rates for the validation set were 97% and 31% for predicted classes-1 and -2 tumors, respectively (p<0.0001). The investigators suggested their preliminary analysis indicates the 28-gene signature is an independent predictor of metastasis risk in the studied cohort of cutaneous melanoma tumors. 

To date, there is a paucity of evidence in the peer-reviewed published medical literature evaluating the clinical utility of the DecisionDx-Melanoma test. The National Comprehensive Cancer Network (NCCN, 2014) Clinical Practice Guideline (CPG) in Oncology recommendations for the clinical staging and workup of melanoma (principles of pathology), states: While there is interest in newer prognostic molecular techniques such as gene expression profiling to differentiate melanomas at low- versus high-risk for metastasis, routine (baseline) genetic testing of primary melanomas (before or following sentinel lymph node biopsy [SLNB]) is not recommended outside of a clinical trial. 

A Cochrane report addressing the primary treatment of cutaneous melanoma (Sladden, 2009) states: ...standard treatment is surgical excision with a safety margin some distance from the borders of the primary tumour. The purpose of the safety margin is to remove both the complete primary tumour and any melanoma cells that might have spread into the surrounding skin. 

An evidence-based review performed by the American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) (Wong, 2012) states that SLNB is an acceptable method for lymph node staging of most individuals with newly diagnosed melanoma as it provides accurate staging for individuals with intermediate-thickness melanomas (Breslow thickness, 1-mm to 4-mm) of any anatomic site. For individuals with thick melanomas (T4, Breslow thickness, greater than [>] 4-mm), SLNB may be recommended for staging purposes and to facilitate regional disease control. For individuals with thin melanoma (T1, Breslow thickness, less than [<] 1-mm), "there is insufficient evidence to support routine SLN biopsy although it may be considered in selected patients with high-risk features when staging benefits outweigh risks of the procedure." For individuals with a positive SLNB, complete lymph node dissection (CLND) is recommended and "achieves good regional disease control." 

In summary, there is insufficient evidence to evaluate the clinical validity and clinical utility of the DecisionDx-Melanoma test. Additional study is required to further validate if gene expression profiling of cutaneous melanoma will accurately identify which individuals are likely to have aggressive disease and how the results of testing would alter treatment plans and improve health outcomes in the surveillance and treatment of high-risk cutaneous melanoma. At this time, it is considered unproven and not known to improve health outcomes. The consensus of opinion among experts regarding the test is that further studies or clinical trials are necessary to determine its maximum tolerated dose, its toxicity, its safety, is efficacy, or its efficacy as compared with the standard means of treatment or diagnosis.