Management of early-stage cutaneous melanoma

Melanoma is a significant health problem, particularly in areas of high sun exposure. In North America, the per capita incidence is rising at an alarming rate. Fortunately, development of techniques for the diagnosis, staging, and treatment of patients with early-stage melanoma have paralleled the rise in melanoma incidence. Approximately 85% of patients diagnosed with melanoma have clinically localized disease at presentation and have their disease classified as early stage. In general, this group has a favorable prognosis. There are, however, multiple known and as yet unknown prognostic factors that lead to heterogeneity in clinical course and outcome for patients with earlystage melanoma. The results of multiple large studies have helped to clarify the optimal margins of resection for primary cutaneous melanomas. To adhere to these margin-width guidelines, the melanoma surgeon must be facile with several techniques for soft tissue defect closure. In addition to techniques for the most commonly performed primary closures, other important techniques used to repair defects resulting from wide local excision include skin grafting and the use of rotational flaps, local advancement flaps, and free flaps. Over the past 3 decades, the approach to patients with clinically negative regional lymph node basins has undergone considerable evolution. Initially, ELND was advocated for patients with intermediate and thick primary melanoma. Although randomized clinical trials overall failed to demonstrate a survival advantage for this more aggressive approach, a survival benefit for certain subsets of patients undergoing ELND was observed in some studies, suggesting that early surgical treatment of the involved regional lymph node basin might be advantageous. This approach, however, exposes patients - the majority of whom do not harbor microscopic disease - to the potential morbidity of a lymph node dissection. Subsequently, the technique of lymphatic mapping and SLNB was introduced. Its ability to identify patients with microscopic lymph node involvement using a minimally invasive approach has obvious advantages over a treatment algorithm that includes routine ELND. Overall, the technique of lymphatic mapping and SLNB has been shown to reliably identify those patients who are most likely to benefit from completion lymph node dissection while sparing patients with negative nodes the morbidity of an additional surgical procedure. It cannot be overemphasized, however, that the prognostic power and ultimate success of this procedure is dependent on excellent communication and coordination between the surgeon, nuclear medicine physician, radiologist, and pathologist. The advent of the SLNB technique has helped to usher in a new era of molecular pathologic analysis of SLNs. Rather than traditional routine histologic examination, SLNs are now subjected to more extensive pathologic examination with serial sectioning, immunohistochemical staining, and, in clinical trials, RT-PCR analysis. In the future, cDNA microarray technology may make possible a genomic approach to melanoma classification, potentially allowing the identification of genetic markers or expression profiles that might be important for diagnosis, determination of prognosis, and even therapy. The particular combination of SLN pathologic and molecular examinations that maximize both sensitivity and specificity (ie, the overall clinical accuracy of metastasis detection) remains a topic of active investigation. Recent reports suggest that the extent of microscopic tumor burden in the SLNs not only is a strong predictor of clinical outcome but also may be a key determinant of likely involvement of additional nodes in the same basin. Indeed, one may conjecture that in a setting of truly submicroscopic disease, the SLNB procedure itself may be both therapeutic and diagnostic; however, this requires further study. Long-term results of studies such as the Sunbelt Melanoma Trial and the Multicenter Selective Lymphadenectomy Trial will address and hopefully answer many of these questions. Other frontiers in the treatment of early-stage melanoma include defining the role of SLNB in patients with T1 primary tumors and determining which patients benefit the most and the least from a completion lymph node dissection following identification of a positive SLN. These are a few of the many questions that remain unanswered in this complex disease.