Primary surgical treatment should be considered for patients with metastatic melanoma. Because of the poor response of melanoma to chemotherapy or radiation therapy, surgery can be the best approach to quickly eliminate detectable disease and return the patient to normal activities. In properly selected patients, surgery can lead to significant palliation and prolongation of survival. This article reviews the principles of patient selection and the potential benefits of surgical management of melanoma metastatic to various sites. Novel adjuvant therapies are being developed to augment the benefits of surgical treatment of advanced melanoma in the future.
Indications for surgical treatment of metastatic melanoma include palliation and prolongation of life. Palliative surgery is considered for patients who have surgically resectable metastases that are either symptomatic or anticipated to cause significant symptoms before the patient dies of the disease. Surgical resection of metastases can also significantly prolong survival from stage IV melanoma, and has been documented in some cases to provide long-term disease-free survival. Considerable clinical judgment, combined with an understanding of the natural history of metastatic melanoma and knowledge of treatment alternatives, is required to determine whether the potential benefits of surgery outweigh the risks in any individual patient.
The prognosis for American Joint Committee on Cancer (AJCC) stage IV melanoma is less than 10% and systemic chemotherapy, immunotherapy, biochemotherapy, or local radiation therapy is usually offered as treatment. Cures are uncommon and these modalities have, almost without exception, been unable to significantly prolong survival. Surgery, however, has the potential to render a patient clinically disease-free in a minimally morbid, cost-effective manner. In selected patients significant improvement in quality of life as well as prolonged survival can be expected.
Morton and colleagues recently reported the results of a randomized prospective trial of Canvaxin (CancerVax Corp, Carlsbad, CA), a whole cell melanoma vaccine. This study (Malignant Melanoma Active Immunotherapy Trial, Stage IV) compared Canvaxin plus bacillus Calmette-Guérin (BCG) versus BCG alone as adjuvant therapy for patients with stage IV melanoma. Of note, all patients underwent complete surgical excision of their metastatic disease as a condition for inclusion in the study. The study was terminated early by the data safety monitoring committee for lack of beneficial effect of the Canvaxin. However, an important outcome was the relatively high 5-year survival rates of both study groups. The combined overall 5-year survival rate in the 496 patients examined was more than 40% despite the inclusion of patients with brain metastases. A similar result occurred in a published trial that studied 41 patients who received a melanoma vaccine after undergoing resection of melanoma metastases. This strategy resulted in a 5-year survival of 46%. In comparison, a recent review of studies including 50 or more patients indicates that overall survival for stage IV melanoma that is not surgically resected clusters around 21% at 5 years. These data seem to support an aggressive surgical approach to localized stage IV melanoma.
Patient selection
The clinical course of systemic melanoma can vary widely among patients. Decisions regarding surgical resection of metastatic melanoma depends on several factors including the sites and numbers of metastases, their rate of growth, types and responses to previous treatment, and the age, overall condition, and desires of the patient. The number of different organs or tissues containing metastases is the most significant factor predicting survival. The median survival for a patient with melanoma metastases in one site is 7 months, for a patient with disease at 2 sites it is 4 months, and when 3 sites are involved median survival is 2 months. The location of the metastasis is also important, with short survival times associated with liver and brain metastases compared with skin, subcutaneous tissue, distant lymph nodes, lung, and bone. The rate of growth of metastatic melanoma is difficult to know, although the time to recurrence can be measured and has a significant impact on survival. Median survival for patients who progress from regional to distant metastasis is 5.6 months if the disease-free interval is less than 18 months, and 8 months if the interval is greater than 18 months. Martinez and Young have recommended criteria for melanoma metastectomy including 1 or 2 visceral sites, 8 or fewer lesions, good functional status, and life expectancy of 3 months or greater. If complete resection cannot be expected, then surgical intervention should be limited to palliation only (ie, relief of gastrointestinal obstruction or management of bleeding). Patients with metastatic melanoma typically initially present with disease at a single site, and this disease is usually amenable to surgical resection. In this case, surgery should be considered the treatment of choice.
Complete staging is important in determining a patient’s eligibility for surgical resection of metastatic melanoma. Whereas routine use of advanced imaging in following patients with early-stage melanoma is generally not advocated, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) help to accurately stage the patient with advanced disease. Ultrasonography has a high sensitivity and specificity for melanoma metastatic to the lymph nodes. A recent comparison of FDG-PET and whole body MRI demonstrated an 86.7% accuracy rate for FDG-PET versus 78.8% for MRI. MRI, however, was more accurate in specific organ sites including the brain and liver, and high-quality spiral CT scans may be better in the detection of small pulmonary metastases.
Although some centers routinely use ultrasound for follow-up surveillance of nodal basins, most practitioners use it to examine a lesion for resectability or to confirm a diagnosis of suspected metastatic disease. There are ultrasonographic findings specific for lymph nodes involved with melanoma, and ultrasonography can help guide fine-needle aspiration for histologic confirmation. When distant metastases have been confirmed and definitive surgery is being considered, patients should be staged with MRI of the brain, CT scan of the thorax abdomen, and pelvis with oral and intravenous contrast, and whole body PET/CT scan. This combination of studies should detect 80% to 90% of early metastatic deposits, and enable clinicians to determine resectability and plan an appropriate surgical procedure that completely removes all detectable disease.
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