Chapter 083. Cancer of the Skin (Part 7) Treatment of Metastatic Disease Melanoma can metastasize to any internal organ, the brain being a particularly common site. Metastatic melanoma is generally incurable, with survival in patients with visceral metastases generally <1 year. Thus, the goal of treatment is usually palliation. Patients with soft tissue and nodal metastases fare better than those with liver and brain metastases. Metastases limited to regional nodes (AJCC stage III disease) warrant a therapeutic lymph node dissection. Surgical excision of a single metastasis to the lung or to a surgically accessible brain site can prolong survival. Stereotactic radiosurgery has been successful in the treatment of isolated brain metastases. Radiation therapy can provide local palliation for recurrent tumors or metastases. Patients who have advanced regional disease limited to a limb may benefit from hyperthermic limb perfusion with melphalan. High complete response rates have been reported, and responses are associated with significant palliation of symptoms. A number of drugs and biological therapies have demonstrated minimal antitumor activity (15–20% partial response rates) in metastatic melanoma, including dacarbazine (DTIC); the nitrosoureas carmustine (BCNU), lomustine (CCNU), and semustine (methyl-CCNU); platinum analogues such as cisplatin and carboplatin; vinca alkaloids such as vincristine, vinblastine, and vindesine; the taxanes paclitaxel and docetaxel; IFN-α; and interleukin 2 (IL-2). Although limited in efficacy, single-agent dacarbazine is still considered the standard treatment. Ongoing trials are attempting to define superior combinations. IL-2 produces response rates similar to those seen with cytotoxic agents; however, active doses usually cause greater toxicity than chemotherapy. Response rates of >50% have been observed with IL-2 for intracutaneous and subcutaneous disease. Melanoma can express cell-surface antigens that may be recognized by host immune cells. These melanoma-associated antigens alone or in combination may make it possible to develop vaccination strategies against melanoma. Such strategies include the use of purified tumor proteins as immunogens and the use of genetically altered tumor cells to elicit a T cell response. Alternative experimental approaches include efforts to expand tumor-specific T cells (either obtained from the tumor as tumor-infiltrating lymphocytes or harvested from the peripheral blood after vaccination) in vitro and transfer them into patients in large numbers. In addition, monoclonal antibodies to tumor antigens are being evaluated. Agents directed against the cell cycle pathways are also currently in trial. All of these experimental approaches will need considerable further development before being applicable on a wide scale. Advances in treating metastatic disease may also prove applicable in the adjuvant setting. The absence of curative therapy for patients with metastatic melanoma underscores the importance of early detection and prevention as strategies to decrease melanoma mortality. Patients with stage 4 melanoma are best treated by medical oncologists with expertise in treating patients with advanced disease. Clinical trials should be considered as an option for this patient group. Nonmelanoma Skin Cancer Nonmelanoma skin cancer (NMSC) is the most common cancer in the United States, with an estimated annual incidence of >1.5 million cases. Basal cell carcinomas (BCCs) account for 70–80% of NMSCs. Squamous cell carcinomas (SCCs), while representing only ~20% of NMSC, are more significant because of their ability to metastasize (Fig. 83-2); they account for most of the 2400 deaths annually. Incidence rates have risen dramatically over the past decade. Figure 83-2 Cutaneous neoplasms. A. Non- Hodgkin's lymphoma involves the skin with typical violaceous, "plum-colored" nodules. B. Squamous cell carcinoma is seen here as a hyperkeratotic crusted and somewhat eroded plaque on the lower lip. Sun-exposed skin such as the head, neck, hands, and arms are other typical sites of involvement. C. Actinic keratoses consists of hyperkeratotic erythematous papules and patches on sun-exposed skin. They arise in middle- aged to older adults and have some potential for malignant transformation. D. Metastatic carcinoma to the skin is characterized by inflammatory, often ulcerated dermal nodules. E. Mycosis fungoides is a cutaneous T cell lymphoma, and plaque stage lesions are seen in this patient. F. Keratoacanthoma is a low- grade squamous cell carcinoma that presents as an exophytic nodule with central keratinous debris. G. This basal cell carcinoma shows central ulceration and a pearly, rolled, telangiectatic tumor border. . Chapter 083. Cancer of the Skin (Part 7) Treatment of Metastatic Disease Melanoma can metastasize to any internal organ, the brain being a particularly common. this patient group. Nonmelanoma Skin Cancer Nonmelanoma skin cancer (NMSC) is the most common cancer in the United States, with an estimated annual incidence of >1.5 million cases. Basal. 70–80% of NMSCs. Squamous cell carcinomas (SCCs), while representing only ~20% of NMSC, are more significant because of their ability to metastasize (Fig. 83-2); they account for most of the 2400