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.