Risk Factors and Predictors of Survival Among Patients with Amelanotic Melanoma Compared to Melanotic Melanoma in the National Cancer Database.

BACKGROUND: Amelanotic melanoma (AM) is a rare form of melanoma lacking pigment. Data on AM risk factors and factors predicting survival are limited. OBJECTIVES: We sought to identify predictors of AM, survival differences in AM and melanotic melanoma, and AM-specific survival rates. METHODS: Using 2004 through 2015 National Cancer Database data, we compared 358,543 melanoma cases to 1,384 AM cases. Multivariable logistic regression identified AM risk factors, and AM survival was explored using Kaplan-Meier and multivariable Cox regression. RESULTS: Increased age; tumor location on the face, scalp, and neck; increased Breslow thickness; metastatic disease; ulceration; and higher mitotic rate were associated with AM. Five- and ten-year survival rates were higher for patients with MM (melanotic melanoma) than AM tumors (75.4% vs. 58.8% and 62.4% vs 45.1%; log-rank P<0.0001). No survival difference was seen after adjusting for staging factors. Among patients with AM, more recent diagnosis was associated with improved survival. Increased age, T4 tumor size, higher N-stage, metastasis, and ulceration predicted poorer survival. No survival advantage was seen for chemotherapy, immunotherapy, or radiation therapy, likely due to confounding. CONCLUSION: AM is more common in older patients on sun-exposed skin and is diagnosed at later stages. Advanced staging at diagnosis explains the survival differences. In patients with AM, regional and metastatic disease were the primary contributors of poorer outcomes. In at-risk patients, the threshold to biopsy should be lower for suspicious nonpigmented lesions.

Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit.

Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. Conclusions and Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.