BACKGROUND Sentinel lymph node biopsy (SLNB) is indicated for the staging of clinically lymph node-negative melanoma of intermediate thickness, but its use is controversial in patients with thick melanoma. METHODS From 2002 to 2012, patients with melanoma measuring ≥4 mm in thickness were evaluated at a single institution. Associations between survival and clinicopathologic characteristics were explored. RESULTS Of 571 patients with melanomas measuring ≥4 mm in thickness and no distant metastases, the median age was 66 years and 401 patients (70.2%) were male. The median Breslow thickness was 6.2 mm; the predominant subtype was nodular (45.4%). SLNB was performed in 412 patients (72%) whereas 46 patients (8.1%) presented with clinically lymph node-positive disease and 113 patients (20%) did not undergo SLNB. A positive SLN was found in 161 of 412 patients (39.1%). For SLNB performed at the study institution, 14 patients with a negative SLNB developed disease recurrence in the mapped lymph node basin (false-negative rate, 12.3%). The median disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) for the entire cohort were 62.1 months, 42.5 months, and 21.2 months, respectively. The DSS and OS for patients with a negative SLNB were 82.4 months and 53.4 months, respectively; 41.2 months and 34.7 months, respectively, for patients with positive SLNB; and 26.8 months and 22 months, respectively, for patients with clinically lymph node-positive disease (P<.0001). The median RFS was 32.4 months for patients who were SLNB negative, 14.3 months for patients who were SLNB positive, and 6.8 months for patients with clinically lymph node-positive disease (P<.0001). CONCLUSIONS With an acceptably low false-negative rate, patients with thick melanoma and a negative SLNB appear to have significantly prolonged RFS, DSS, and OS compared with those with a positive SLNB. Therefore, SLNB should be considered as indicated for patients with thick, clinically lymph node-negative melanoma.

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Background: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. VOYAGER PAD demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. Methods: The VOYAGER PAD trial randomized patients with PAD after surgical and endovascular LER to rivaroxaban 2.5mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary endpoint was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. International Society on Thrombosis and Haemostasis (ISTH) bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. Results: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared to placebo, rivaroxaban reduced the primary endpoint consistently regardless of LER method (p-interaction 0.43). Following surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (HR 0.81, 95% CI 0.67 - 0.98; p=0.026). In the overall trial, TIMI major bleeding and ISTH major bleeding were increased with rivaroxaban. There was no heterogeneity for TIMI major bleeding (p-interaction 0.17) or ISTH major bleeding (p-interaction 0.73) based on LER approach. Following surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence 1.3% and 1.4% respectively (HR 0.88, 95% CI 0.39-1.95; p=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (p=0.95) and postprocedural bleeding requiring intervention (p=0.93) were not significantly increased. Conclusions: The efficacy of rivaroxaban is associated with a benefit in surgical LER patients. While bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage or postprocedural bleeds requiring intervention. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02504216

pMLS is an STS subtype with favorable tumor biology and an extremely low-rate of local recurrence. Our results suggest that multimodality therapy may not be necessary for all pMLS.