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.

The role of sentinel lymph node biopsy in patients with ductal carcinoma in situ or with locally advanced breast cancer receiving neoadjuvant chemotherapy.

BACKGROUND: A significant number of patients who are initially diagnosed with pure DCIS will harbor missed or occult invasive disease at their definitive surgery. To provide more accurate staging information and to avoid a second operation, some investigators believe that SLN mapping should be performed in DCIS patients. The role of SLN biopsy after neoadjuvant chemotherapy in patients with advanced breast cancer is controversial. METHODS: A review of the literature was performed to determine the role of SLN biopsy in patients with DCIS or advanced breast cancer receiving neoadjuvant chemotherapy. The success rate of SLN biopsy after neoadjuvant chemotherapy was investigated as well as the percentage of positive SLNs in patients with DCIS. RESULTS: Two consecutive studies revealed metastatic disease to the regional lymph nodes in up to 13% of DCIS patients. In addition, 10% of DCIS patients were upstaged to infiltrating ductal carcinoma at their definitive therapy. The ability of the SLN to predict the status of the remaining non-SLNs after neoadjuvant chemotherapy is unknown. False-negative rates range from 0% to 33%. The success rate for SLN identification for the combined series varies from 84% to 97%. CONCLUSIONS: SLN biopsy is a minimally invasive technique that can be used to evaluate the regional nodal status of DCIS patients. Performing a SLN biopsy during the initial surgical procedure may avoid a second operation in some DCIS patients who are diagnosed with invasive disease at their definitive operation. The success rate of sentinel node identification does not seem to be altered after neoadjuvant therapy. However, the ability of the SLN to predict the pathologic status of the adjacent non-SLNs remains unknown. Therefore, until further prospective randomized trials are conducted, it cannot be assumed that all the regional nodes have the same biologic response to chemotherapy as the SLN.

Worldwide experience with lymphatic mapping for invasive breast cancer.

Lymphatic mapping and sentinel lymph node (SLN) biopsy have changed the standard of surgical care for women with invasive breast cancer. The rate of successful axillary SLN identification varies from 90% to 99%. Recurrence rates after a negative SLN biopsy have been remarkably low. Internal mammary node drainage has been noted in 8% to 22% of cases, but whether to harvest these extra-axillary sites of drainage remains controversial. Because of the low morbidity associated with the lymphatic mapping procedure, all women with invasive breast cancer should be considered as candidates for this more accurate staging technique.

National trials involving lymphatic mapping for melanoma: the Multicenter Selective Lymphadenectomy Trial, the Sunbelt Melanoma Trial, and the Florida Melanoma Trial.

Radioguided surgery and lymphatic mapping provide more accurate staging and a less morbid operation for the patient with malignant melanoma. It has rapidly become the standard of care for the nodal staging of this disease. Regional and national trials have been designed to address various questions that concern the application of this technique. The Multicenter Selective Lymphadenectomy Trial (MSLT), being performed by Donald Morton at the John Wayne Cancer Institute, is a national trial that will address whether this surgical strategy provides a survival benefit for patients. The national, industry-sponsored SunBelt Melanoma Trial (SBMT), with Kelly McMasters from the University of Louiville as the principle investigator, will determine the role of molecular staging in patients who undergo sentinel lymph node (SLN) harvest. In another arm of the study, the role of adjuvant interferon alfa (IFN) will be examined in patients with minimal disease in the regional basin, those patients with just one microscopically positive SLN. Finally, the Florida Melanoma Trial (FMT), with the central office and laboratory located at the Lakeland Regional Cancer Center, is a regional, industry-sponsored trial that will determine whether all patients with a positive SLN need to undergo a complete lymph node dissection (CLND) of the affected basin. Clinicians await the results of these three trials to help to determine the final role of radioguided surgery in patients with malignant melanoma.

The staging of malignant melanoma and the Florida Melanoma Trial.

Lymphatic mapping and sentinel lymph node (SLN) biopsy have changed the standard of care for patients with malignant melanoma, by providing a less morbid procedure to obtain the nodal staging information that is critical for therapeutic decisions. Detailed examination of the SLN identifies patients who have an increased risk for recurrence and death. Patients whose melanoma is upstaged with very sensitive assays based on reverse transcriptase polymerase chain reaction technology are better targeted for clinical trials or surgical or adjuvant therapies. In the future, melanoma may be "ultrastaged" by examining the SLNs, peripheral blood, and bone marrow. This may improve identification of patients who are surgically cured of their disease and therefore can be spared the side effects of more radical surgery or the toxicities of adjuvant therapy. The lymphatic mapping procedure is the most accurate way to determine the tumor status of the regional lymph nodes.

Lymphatic mapping and sentinel lymph node biopsy for breast cancer.

Lymphatic mapping and sentinel lymph node mapping have changed the standard of surgical care for patients with melanoma and have the potential to do the same for women with breast cancer. The technique will result in more accurate disease staging and in less morbidity. Preoperative lymphoscintigraphy and the intraoperative mapping technique are being standardized across the country. With the lymphatic mapping technique, approximately 10% of the so-called histologic negative population will be more accurately staged. National trials are ongoing to determine the clinical significance of the missed micrometastatic

Sentinel Node Biopsy in Breast Cancer: An Overview.

The most powerful predictor of survival in breast cancer is the presence or absence of lymph node metastases. Lymphatic mapping and sentinel node biopsy is a new technique that provides more accurate nodal staging compared to routine histology for women with breast cancer without the morbidity of a complete lymph node dissection. Sentinel lymph node biopsy is a more conservative approach to the axilla that requires close collaboration between the surgical team, nuclear medicine, and pathology. National trials are investigating the clinical relevance of the upstaging that occurs with a more intense examination of the sentinel node. Since complaints due to the axillary node dissection are a common occurrence after definitive breast cancer surgery, if the side effects of the level I and II node dissection can be avoided, particularly in the node-negative population, a major advance in treating this disease will be made.