Surgical Treatment of Pulmonary Metastases from Melanoma: Emerging Options

Malignant melanoma (MM) is rapidly becoming a major health problem in the USA and in Europe. It has been estimated that more than 55,000 Americans developed MM in 2004, and that about 8,000 ultimately died of it (1). More than one third of patients operated for MM develop tumor recurrence; melanoma patients’ annual risk of death in Stage IV of the American Joint Committee on Cancer (AJCC) has been estimated to be about 20% during the first 3 years (2). The site of relapse is a very important predictor of survival. Regional lymph node recurrences in fact, may be surgically resected and 5-year survival rate have been reported to be between 20% and 50% (3-4). Distant metastases (MTS), both in visceral and non-visceral sites, reported a 5-year survival of approximately 5% (5-7); for these patients surgery is not often feasible and systemic treatment (chemotherapy, immunotherapy, radiotherapy) is sometimes the curative option. Lung is the second most common site for metastatic MM spread (8). The annual probability of developing lung MTS progressively increases from 10% at 5 years to 17% at 15 years after the resection of the primary tumor (9). Lung MTS are usually asymptomatic, sometimes multiple, occasionally detected with radiological imaging during patient follow-up. Once lung MTS has developed, the possible surgical treatment remains controversial. Even if a clear clinical advantage in overall survival (OS) after resection of pulmonary MTS from osteogenic sarcoma, soft tissue sarcoma, non-seminomatous testicular neoplasms, colorectal and renal cell carcinoma has been demonstrated, 5-year survival rates in melanoma patients were lower, ranging between 5% and 31% (10-12). These ranges indicate how a preoperative patient selection is mandatory. In fact, only 10-35% of all metastatic melanoma patients are suitable for a complete surgical resection (13). Systemic treatments including chemotherapy, radiotherapy, immunotherapy and more recently molecular target agents, demonstrated a partial clinical response only, with severe adverse effect and a dramatic impact on patient’s quality of life (QOL), providing little, if any, attested survival benefit. Chemotherapy regimens may include: dacarbazine, cisplatin and carmusine, alone or in combination with a variety of immunotherapies, including cytokines, monoclonal antibodies and vaccination strategies with synthetic peptides, naked DNA, dendritic cells and recombinant viruses (14-17). Unfortunately, results are presently