Metastatic Melanoma

Excerpt

Incidence of primary cutaneous melanoma has increased steadily for several decades and remains the most lethal form of cutaneous neoplasm, but over the last three decades, the overall survival rates have remained relatively constant. From 2004 to 2009, the rates of stage IV metastatic cancer ranged from 26.4% to just 4.7%. Mucosal and ocular melanoma typically have worse prognoses. Melanoma was once considered among the most resistant cancers to traditional therapies such as chemotherapy, radiation, and even targeted therapies in their early stages. A dramatic improvement in quality of life and overall survival has resulted from new targeted immunotherapies for patients with metastatic melanoma. In this review, we discuss the current treatment landscape of metastatic melanoma.

Melanoma is distinct from non-melanoma skin cancers in that it tends to spread locally, regionally, and distantly. An individual's risk of metastasis is directly related to the depth of invasion and ulceration of their primary lesion. The early stages of cancer metastasis involve invasion, angiogenesis, extravasation, dissemination, and colonization of the target organ. It is often believed that metastasis is a linear process from local disease to nodal metastasis to distant metastasis. Patients with node-negative disease and those who undergo sentinel lymph node basin can still present with distant metastatic disease, and complete lymph node dissection has not been proven to offer a survival benefit to patients with node-positive disease.

There are reports of the transfer of melanoma to the recipient from an organ transplant, even when the transplant was performed years after the donor was diagnosed with thin melanoma. Such distant seeding suggests early metastatic melanoma may be common, and distant metastasis is likely controlled by a combination of microenvironment and immunity. A search for metastasis-specific genetic alterations in melanoma has not been particularly successful, although copy number alterations, MITF amplification, TERT promoter mutations, and CDKN2A loss occur at higher frequencies in metastatic melanomas than in primary melanomas. Melanoma has a propensity for spreading to the central nervous system (CNS)/brain, leading to high morbidity and resistance to therapy.