Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.
Background
For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery±SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial.
Methods
Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation. We evaluated recurrence site, therapy (selected by treating clinician), and survival after stage IV diagnosis.
Results
Of 291 patients with complete data for stage IV recurrence, 161 (55%) underwent surgery±SMT. Median survival was 15.8 vs. 6.9 months and 4-year survival was 20.8% vs. 7.0% for patients receiving surgery±SMT vs. SMT alone (p<0.0001; HR 0.406). Surgery±SMT conferred a survival advantage for patients with M1a (median >60 months vs. 12.4 months; 4-year 69.3% vs. 0; p=0.0106), M1b (median 17.9 vs. 9.1 months; 4-year 24.1% vs. 14.3%; p=0.1143), and M1c (median 15.0 vs. 6.3 months; 4-year 10.5% vs. 4.6%; p=0.0001) disease. Patients with multiple metastases treated surgically had a survival advantage, and number of operations did not reduce survival in the 67 patients (42%) who had multiple surgeries for distant melanoma.
Conclusions
Our findings suggest that over half of stage IV patients are candidates for resection and exhibit improved survival over patients receiving SMT alone, regardless of site(s) and number(s) of metastases. We have begun a multicenter randomized phase III trial comparing surgery versus SMT as initial treatment for resectable distant melanoma.
Prolonged survival was observed in patients who received postoperative active immunotherapy with Canvaxin therapeutic cancer vaccine. The correlation of survival with vaccine-DTH responses but not PPD-DTH indicates a treatment-specific effect. These findings suggest that adjuvant active specific immunotherapy should be considered after cytoreductive surgery for advanced melanoma.
Sentinel lymph node dissection is a minimally invasive surgical technique for staging of breast carcinoma. The optimal pathologic examination of the sentinel node (SN) has not yet been determined. Our standard protocol for evaluation of the SN in patients with breast cancer included frozen section at one level, plus paraffin sections at two levels, separated by 40 microm, and stained with hematoxylin and eosin and cytokeratin immunohistochemistry (IHC) at each paraffin section level. In the current study, we evaluated the use of step sections and cytokeratin IHC in 60 SNs (42 consecutive patients) that were tumor-negative on frozen section and hematoxylin and eosin staining at permanent section levels 1 and 2. The SN were reexamined with cytokeratin IHC at eight additional levels (levels 3-10) of the paraffin block, each separated by 40 microm. Previous IHC sections from levels 1 and 2 had shown micrometastases in nine SNs (eight patients) and no tumor cells in the remaining 51 SNs (34 patients). Of the 51 previously negative SNs, only two (4%) SNs from one (3%) patient had metastatic carcinoma cells in levels 3-10. Thus, the additional step sections with cytokeratin IHC did not significantly increase the number of patients with tumor-positive SNs. We currently recommend that the SN be examined with cytokeratin IHC at two levels of the paraffin block. This should optimize sentinel lymph node dissection as a staging technique and minimize the labor and financial burden associated with multiple step sections and IHC stains.
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