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Melanoma is the most aggressive form of skin cancer. Although its incidence pales in comparison to basal cell carcinoma and squamous cell carcinoma (SCC), melanoma is the cause of approximately 75% of all skin cancer–related deaths. The majority of patients who are diagnosed with early-stage melanoma have very good outcomes with appropriate surgical management. In contrast, patients with regional and distant metastases have historically had poorer outcomes, because agents that have proven efficacious in other malignancies (eg, chemotherapy) generally have had limited activity in this disease. However, the management of melanoma is evolving rapidly due to parallel breakthroughs in the understanding and targeting of the molecular drivers of this disease and the regulators of the antitumor immune response. These advances are rapidly translating into improved outcomes in patients with advanced melanoma and the consideration of new diagnostic and therapeutic approaches across the full continuum of this disease.




Melanoma is the fifth most common cancer in men and the sixth most common cancer in women in the United States (1). The age-adjusted incidence for cutaneous melanoma from 2007 to 2011 was 21.3 per 100,000 per year in the United States (2). In contrast to the favorable trends that have been observed with almost all other major cancers, the annual incidence of melanoma continues to rise by approximately 2% to 3% per year and has increased overall more than 500-fold since the 1950s (3).


A number of factors have been identified that correlate with an increased risk of being diagnosed with melanoma (Table 41-1). Many of these factors reflect the strong association between melanoma and ultraviolet radiation (UVR) exposure, which is supported by epidemiologic studies (4). More recently, whole-exome sequencing studies have demonstrated that melanomas are characterized by a higher rate of somatic mutations than almost all other solid tumors and that the majority of mutations that are identified bear the molecular signature of UVR-related DNA damage (5). Several risk assessment aids have been developed to identify high-risk individuals, including the Melanoma Risk Assessment Tool (MRAT), which is available online ( Individuals at increased risk of developing melanoma should have awareness of the signs of melanoma and regular screening examinations.

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Table 41-1Factors Associated With Increased Risk of Melanoma

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