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LEARNING OBJECTIVES

LEARNING OBJECTIVES

Upon completion of the chapter, the reader will be able to:

  1. Identify the risk factors associated with skin cancer.

  2. Devise a plan of lifestyle modifications for the prevention of skin cancer.

  3. Discuss the importance of mutation testing in the therapy selection for metastatic melanoma treatment.

  4. Explain the goals of therapy for the treatment of the different nonmelanoma and melanoma stages.

  5. Compare and contrast the available pharmacologic treatment options for nonmelanoma and melanoma skin cancer.

  6. Suggest management options for patients experiencing adverse effects of pharmacologic therapy.

INTRODUCTION

Skin cancer is the most common malignancy in the United States with over 5 million new diagnoses reported in roughly 3 million individuals as of 2012. Of these, more than 95% are diagnosed with nonmelanoma skin cancer (NMSC), while the rest of skin cancer diagnoses are accounted for by malignant melanoma (MM).1,2 NMSC incidence increased 300% since 1994 and continues to rise due to increasing high-risk populations, such as organ transplant and photosensitizing medication users. NMSC consists of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), which originate in the basal cell layer and the hair follicle stem cells, respectively.3 MM differs substantially from NMSC with regard to its metastatic potential, prognosis, and treatment options.

MALIGNANT MELANOMA

EPIDEMIOLOGY AND ETIOLOGY

MM is the most diagnosed malignancy in young adults and ranks among top five most incident cancer diseases in the United States, representing approximately 5% of all cancer cases. Although accounting for less than 3% of the skin cancer diagnoses, MM is responsible for the majority of skin cancer deaths (75%).1,4 With a median age at diagnosis of 64, about half of the MM cases were diagnosed between ages 55 and 74. Approximately 91,270 new cases are predicted to occur in 2018, a forecast impacting males more than females, according to the Surveillance Epidemiology and End Results (SEER) age-adjusted analyses.5 However, these figures may be underestimated since many superficial and in-situ melanomas are treated in outpatient settings and, thus, not included in the SEER registry.

RISK FACTORS

MM risk factors include environmental and host factors. Image not available. Sun exposure and ultraviolet-based artificial tanning are the main environmental triggers for melanoma occurrence. While MM can occur in any ethnic group and also on less exposed areas of the body, individuals with genetic susceptibility may develop exacerbated skin reactions to sun or ultraviolet radiation (UVR), particularly UVB. Interestingly, although UVB-induced DNA damage was determined to be lifetime cumulative, the most prevalent (over 70%) UV-induced genetic modification—C to T—is, paradoxically, irrelevant for most well-known melanoma mutations, BRAF V600E, and NRAS Q61L/R.6 Yet, recent evidence supports a UVR-induced mutation mechanism for melanoma occurrence: the hot-spot mutations in RAC1, STK19, and PPP6C.7

Further, well-documented UVR-induced TP53...

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