Lymph node metastasis in melanoma: a debate on the significance of nodal metastases, conditional survival analysis and clinical trials.

While there is no doubt that regional lymph node metastases are an enormously important factor in melanoma staging and treatment, the biology behind this significance and its precise implications for treatment planning have been a leading controversy in melanoma and other solid tumors for over a century. Recent clinical data, including data from prospective randomized clinical trials have refined our understanding of the process of nodal metastases and the advantages and disadvantages of different clinical management strategies. This review presents two points of view in this debate and discusses the results of new data analyses as well as pivotal clinical trials informing the discussion.

Breast Lymphatic Mapping and Sentinel Lymph Node Biopsy: State of the Art: 2015.

Lymphatic mapping with sentinel lymph node biopsy (SLNB) was introduced in the 1990s as a method to stage the nodal axilla in women with breast cancer. Very quickly the technique became the standard of care because pathologic staging was more accurate and sensitive and the surgical procedure resulted in low morbidity. SLNB has continued to evolve, and the applications in breast cancer have been expanded. A review of the published data was performed to update the lymphatic mapping technique and identify key issues and trends in the application of SLNB in women with breast cancer in 2015. The importance of axillary staging continues to effect the surgical treatment of patients with breast cancer. Originally described for patients with invasive cancer, the technique now plays an important role in staging women with ductal carcinoma in situ or recurrent breast cancer and patients with advanced breast cancer who are receiving neoadjuvant chemotherapy. Histologic examinations have incorporated multiple sectioning and immunostains. The morbidity has been low, and techniques for limiting lymphedema are being introduced. Lymphatic mapping will continue to play an important role in the treatment of women with breast cancer. The SLNB will evolve by eliminating the need for radioactivity in the operating room, and the technique will become more accurate and used in expanded indications by incorporating preoperative imaging and intraoperative guidance procedures.

Evidence for a better nodal staging system for melanoma: the clinical relevance of metastatic disease confined to the sentinel lymph nodes.

BACKGROUND: The hypothesis tested in this study was whether patients with stage III metastatic melanoma confined to their sentinel lymph nodes (SLNs) had a more favorable prognosis than patients who had SLN and non-SLN (NSLN) metastases. METHODS: Patients were identified who were clinically negative in their regional basins but with lymphatic mapping were found to have positive SLNs (331 patients). All patients subsequently underwent a complete lymph node dissection of the lymphatic basin involved, and the total number of metastatic SLNs and NSLNs were documented. RESULTS: As the regional metastatic disease involves NSLNs, disease-free survival (DFS) and overall survival (OS) decreases. For patients with a total of 2 nodes positive, those with disease confined to the SLNs had a significant better prognosis (DFS and OS: P < .00001) than those in whom 1 SLN and 1 non-SLN was involved. This difference was apparent for those patients with N2 and N3 disease (2 or more nodes positive in their regional basin). A multivariate regression analysis that included Breslow thickness, ulceration, number of positive nodes, and NSLN positivity showed that NSLN positivity (P = .0019) was the most powerful predictor of DFS and OS. CONCLUSIONS: When metastatic melanoma overwhelms the SLN and involves NSLNs, the biologic behavior changes to portend a worse survival, regardless of the total node count positive. These data make the argument that the current N staging system should be changed to incorporate SLN vs NSLN involvement.

The changing face of malignant melanoma.

BACKGROUND AND OBJECTIVES: There is currently an epidemic of malignant melanoma occurring in the United States. At the same time there has been a heightened awareness for early detection of melanoma in the professional ranks as well as in the lay population. A database review was performed to investigate the changing patterns of melanoma presentation during a 2 decade time period in the State of Florida. METHODS: This report is based on data collected in a prospective fashion from three institutions that shared a single melanoma database initially established in 1987. Four 5-year time periods were arbitrarily selected for the study: 1989-1993, 1994-1998, 1999-2003, and 2004-2008. Patients were grouped by their date of initial diagnosis. RESULTS: A total of 7,580 patients were registered in the database during the study intervals. Multiple group comparisons by Chi-Square analysis showed that there were significant differences among the four groups in tumor thickness at diagnosis, stage of disease at diagnosis and disease-free survival (DFS). The DFS rate for all patients diagnosed with melanoma has progressively improved over the last 20 years (P < 0.0001). CONCLUSIONS: Even though there is an epidemic of malignant melanoma occurring in the United States, it appears that patients are being diagnosed earlier with thinner lesions that are capable of being cured with simple surgical techniques.

Regional Therapy for Recurrent Metastatic Melanoma Confined to the Extremity: Hyperthermic Isolated Limb Perfusion vs. Isolated Limb Infusion.

Melanoma patients with recurrent disease confined to an extremity can be offered one of two regional therapies that both give high complete response rates. Isolated limb infusion (ILI) is a newer technique performed with catheters and tourniquets that has a reduced potential morbidity, decreased efficacy and does not treat the regional nodal basin. Hyperthermic Isolated Limb Perfusion (HILP) is an open surgical technique that includes removal of the regional nodal basin as part of the surgical procedure. An analysis was performed of the rates of regional nodal disease in this patient population to determine the percentage of patients with stage III metastatic disease to the lymph nodes that would be under treated with the ILI technique. A total of 229 patients underwent a HILP for melanoma with regional lymph node dissection as is our standard between July 1987 and December 2009. Ninty-two of the 229 patients (40%) had metastatic regional nodal disease documented at the time of the HILP procedure. HILP is the only technique that addresses all micrometastatic disease on the extremity.