Treatment Option Overview
Melanomas that have not spread beyond the site at which they developed are highly curable. Most of these are thin lesions that have not invaded beyond the papillary dermis (Clark level I-II; Breslow thickness =1 mm). The treatment of localized melanoma is surgical excision with margins proportional to the microstage of the primary lesion; for most lesions 2 mm or less in thickness, this means 1 cm radial re-excision margins.[1,2]
Melanomas with a Breslow thickness of 2 mm or more are still curable in a significant proportion of patients, but the risk of lymph node and/or systemic metastasis increases with increasing thickness of the primary lesion. The local treatment for these melanomas is surgical excision with margins based on Breslow thickness and anatomic location. For most melanomas more than 2 mm to 4 mm in thickness, this means 2 cm to 3 cm radial excision margins. These patients should also be considered for sentinel lymph node biopsy followed by complete lymph node dissection if the sentinel node(s) are microscopically or macroscopically positive. Sentinel node biopsy should be performed prior to wide excision of the primary melanoma to ensure accurate lymphatic mapping. Patients with melanomas that have a Breslow thickness more than 4 mm should be considered for adjuvant therapy with high-dose interferon.
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Some melanomas that have spread to regional lymph nodes may be curable with wide local excision of the primary tumor and removal of the involved regional lymph nodes.[3,4,5,6] In a prospective randomized controlled trial (EST-1684), adjuvant high-dose interferon was shown to increase relapse-free survival (RFS) and overall survival (OS) when compared to observation.[7] A subsequent randomized trial (EST-1690) conducted by the same group of investigators using the same high-dose interferon regimen confirmed the RFS but not the OS advantage.[8] A third randomized trial (SWOG-8593) again demonstrated both a disease-free survival (DFS) and OS advantage to high-dose interferon when compared to a ganglioside vaccine.[9] Clinicians should be aware that high-dose interferon regimens have substantial side effects, and patients should be monitored closely. Adjuvant therapy with lower doses of interferon have not been consistently shown to have an impact on either RFS or OS.[10] Adjuvant chemotherapy does not improve survival. A multicenter phase III randomized trial (SWOG-8593) of patients with high-risk primary limb melanoma did not show a benefit from isolated limb perfusion with melphalan in regard to DFS or OS when compared to surgery alone.[11]
Melanoma that has spread to distant sites is rarely curable with standard therapy, though high-dose interleukin-2 (IL-2) has been reported to produce durable responses in a small number of patients.[12,13] In patients with systemic metastasis confined to one anatomic site, long-term survival is occasionally achieved by complete resection of all metastatic disease.[14,15,16,17] All patients with distant metastasis are appropriately considered candidates for clinical trials exploring new forms of treatment, including combination chemotherapy, biological response modifiers (such as specific monoclonal antibodies, interferons, IL-2, or tumor necrosis factor-alpha), vaccine immunotherapy, or biochemotherapy (chemoimmunotherapy).
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