Background Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. Methods We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (±SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3±1.8% vs. 64.7±2.3%; hazard ratio for recurrence or metastasis, 0.76; P = 0.01), and those with thick melanomas, defined as >3.50 mm (50.7±4.0% vs. 40.5±4.7%; hazard ratio, 0.70; P = 0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1±4.8% among those with metastasis versus 85.1±1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0±7.0% and 64.6±4.9% (hazard ratio, 1.75; P = 0.03). Biopsy-based management improved the 10-year rate of distant disease–free survival (hazard ratio for distant metastasis, 0.62; P = 0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P = 0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted. Conclusions Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease–free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. (Funded by the National Cancer Institute, National Institutes of Health, and the Australia and New Zealand Melanoma Trials Group; ClinicalTrials.gov number, NCT00275496.)

Background[99mTc]Tilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared [99mTc]tilmanocept to vital blue dye.MethodsPatients received [99mTc]tilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by [99mTc]tilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials.ResultsFifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by [99mTc]tilmanocept, for 98.7 % concordance (p < 0.001). [99mTc]Tilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes). [99mTc]Tilmanocept detected at least one node in more patients (n = 150) than blue dye (n = 138, p = 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by [99mTc]tilmanocept, whereas blue dye detected only 36 (80 %) of 45 (p = 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by [99mTc]tilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by [99mTc]tilmanocept. No serious adverse events were attributed to [99mTc]tilmanocept.Conclusions[99mTc]Tilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.

Melanoma-in-situ (MIS) represents 45% of all melanomas. The margins of MIS are often poorly defined with extensive subclinical disease. Standard fusiform excision with 5-mm margins results in positive margins in up to a third of cases. To decrease the incidence of involved margins, we use a staged excision approach for MIS. First, patients undergo excision under local anesthesia of a 2- to 3-mm "contoured" rim of tissue optimally 5 mm beyond the visible extent of the lesion. Formalin-fixed paraffin-embedded en face sections from this excision are then evaluated, if necessary with the aid of immunohistochemical stains. Any positive margins are further excised. When all margins are negative, the central area is then excised and reconstructed. A total of 61 patients with MIS or lentigo maligna melanoma underwent staged contoured excisions from 2004 to 2007 at Moffitt Cancer Center. We analyzed data only from patients with MIS of the head and neck. Patients with known invasive melanoma or non-head and neck primary disease were excluded. Demographics, tumor characteristics, margin status, number of stages, and type of reconstruction and recurrences were evaluated. Forty-nine patients with MIS of the head and neck, 28 (57%) male and 21 (43%) female, 42 to 88-years-old (median 72; mean 70), underwent staged contoured margin excision before definitive central tumor excision and reconstruction. The final surgical defect size ranged from 2 to 130 cm(2) (median 16 cm(2)). Twelve patients (24%) required reexcision of at least one margin; the median number of reexcisions was 1 (range 1-2). There seemed to be a positive association between lesion size and margin status (as well as number of excisions needed to clear the margin). Unsuspected invasive melanoma was found in the central specimen in six patients (12%). Even small tumors could have unsuspected invasive melanoma: invasive cancer was seen in 4 (21%) of 19 tumors < or =2 cm in greatest dimension and 2 (7%) of 30 > 2 cm, respectively. Surgical defects were reconstructed with flaps in 18 (37%), full-thickness grafts in 20 (41%), and split-thickness grafts in 10 patients (20%). Median time from first margin excision to completion/final reconstruction was 7 days (range 7-63 days). No local recurrences have been reported at a median follow-up of 14 months (range 1-36 months). This technique allows for careful margin analysis and subsequent central tumor excision with simultaneous reconstruction. This approach minimizes the need for a second major operation, which would have been necessary in 24% of our patients if treated by a one-stage excisional approach. It is noteworthy that 12% of MIS patients had invasive melanoma in the final excision specimen. This reinforces the importance of adequate full-thickness biopsies of suspicious pigmented lesions before any type of surgical management. With short follow-up, local control has been achieved by this technique in 100% of cases.

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BACKGROUND The purposes of this study were 1) to determine the impact of primary tumor-related factors on the prediction of the sentinel lymph node (SLN) status and 2) to identify clinical and pathologic factors associated with survival in Merkel cell carcinoma (MCC). METHODS An institutional review board–approved, retrospective review of patients with MCC treated between 1988 and 2011 at a single center was performed. Patients were categorized into 5 groups: 1) negative SLN, 2) positive SLN, 3) clinically node-negative but SLN biopsy not performed, 4) regional nodal disease without a known primary tumor, and 5) primary MCC with synchronous clinically evident regional nodal disease. Factors predictive of the SLN status were analyzed with logistic regressions, and overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox models and competing risk models assuming proportional hazards, respectively. RESULTS Three hundred seventy-five patients were analyzed, and 70% were male; the median age was 75 years. The median tumor diameter was 1.5 cm (range, 0.2–12.5 cm), and the median tumor depth was 4.8 mm (range, 0.3–45.0 mm). One hundred ninety-one patients underwent SLN biopsy, and 59 (31%) were SLN-positive. Increasing primary tumor diameter and increasing tumor depth were associated with SLN positivity (P =.007 and P =.017, respectively). Age and sex were not associated with the SLN status. Immunosuppression, increasing tumor diameter, and increasing tumor depth were associated with worse OS (P <.01, P =.003, and P <.025, respectively). DSS differed significantly by group and was best for patients with a negative SLN and worst for those with primary MCC and synchronous clinically evident nodal disease (P =.01). CONCLUSION For patients with MCC, increasing primary tumor diameter and increasing tumor depth are independently predictive of a positive SLN, worse OS, and worse DSS. Tumor depth should be routinely reported when primary MCC specimens are being evaluated histopathologically.