Chapter 29: Management of Advanced Nonmelanoma Skin Cancer

EPIDEMIOLOGY OF NONMELANOMA SKIN CANCER

Skin cancers are divided into two main groups: malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). The term “NMSC” encompasses a wide variety of skin cancers including basal cell carcinomas (BCC), cutaneous squamous cell carcinomas (cSCC), dermatofibrosarcoma protuberans (DFSP), cutaneous lymphomas, adnexal tumors, and Merkel cell carcinoma (MCC), and only excludes malignancies involving melanocytes. BCC and cSCC comprise the vast majority of NMSC tumors (estimated between 75% and 80% and 20% and 25%, respectively)^1,2 and their incidence is approximately 18 to 20 times higher than that of MM.³ This chapter will focus on the management of advanced BCC, cSCC, DFSP, and MCC.

The incidence of NMSC is highest in Australia and the lowest in parts of Africa.⁴

In the United States, the total number of NMSC cases is reported to be higher than lung, breast, prostate, and colon cancers combined.⁵ Over one million new cases of NMSC are diagnosed each year in the United States alone, and this has continued to increase at a rate of approximately 3% to 8% since the 1960s.^3,6 NMSCs are also widely believed to be the most commonly diagnosed malignancy worldwide.^2,7

BASAL CELL CARCINOMAS

BCC Incidence and Risk Factors

BCC is the most common type of cancer worldwide.⁸ In the United States, the estimated annual incidence is estimated to be 0.1% to 0.5%.⁹ It is especially common in light-skinned populations, with the estimated lifetime risk of developing BCC up to 30% in the United States white population.¹⁰ The incidence is about 30% higher in men than in women,^11–13 and increases with age.¹⁴ Interestingly, the incidence of BCC among Americans younger than 40 years of age, especially among women, seems to be increasing.¹⁵

Both environmental and genetic factors play a role in the development of BCC: these include ultraviolet (UV) radiation,^16–19 arsenic exposure,^20–22 history of radiation therapy (RT),^23–25 immunosuppression (from various causes including solid organ transplantation, HIV infection, or chronic steroid use secondary to autoimmune disorders),^26,27 fair skin,²⁸ light-colored eyes, red hair, northern European ancestry, older age, childhood freckling, history of blistering sunburns, history of tanning bed use,²⁹ smoking,^19,30 and genetic conditions, such as basal cell nevus syndrome (BCNS) and epidermolysis bullosa.^{17,18,29,31–33} Of these, UV radiation is one of the most important causes of BCC. In addition to the total radiation dose, the timing and mode of exposure also seem to contribute to BCC development. Recent studies showed that acute, intense incremental UV exposure increases BCC risk more than similar doses of UV radiation delivered in a more chronic fashion over the same total period of time.^26,34 There have also been studies suggesting that childhood and adolescence are critical periods for establishing adult BCC risk, thus highlighting the ...