Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma

Abstract

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.)

Tumor PD-L1 expression, immune cell correlates and PD-1+ lymphocytes in sentinel lymph node melanoma metastases

“…Modern Pathology (2015) 28, 1535-1544; doi:10.1038/modpathol.2015.110; published online 25 September 2015 Sentinel lymph node biopsy has become the standard of care for accurately staging primary cutaneous melanomas ≥ 1 mm in Breslow thickness in most major melanoma treatment centers worldwide. 1 Patients with a positive sentinel lymph node that undergo completion lymphadenectomy still have variable 5-year survival rates ranging from 39-70% depending on factors such as the number of tumorbearing nodes, sentinel lymph node tumor burden, presence or absence of primary tumor ulceration, and thickness of the primary melanoma. 2 These patients may benefit from adjuvant therapies, which act to reduce the risk of relapse and dissemination to distant sites.…”

High-risk Cutaneous Squamous Cell Carcinoma

“…[57][58][59] Its role in the management of cSCC of the head and neck remains opaque. 60 In the case of melanoma, while sensitivity of 87.5 to 89.2% has been reported in meta-analysis and prospective trials respectively, data supporting its effect on survival outcomes are lacking.…”

“…60 In the case of melanoma, while sensitivity of 87.5 to 89.2% has been reported in meta-analysis and prospective trials respectively, data supporting its effect on survival outcomes are lacking. 59 Limited studies exist to suggest a clear role for SLNB in cSCC. One review of 173 patients with high-risk cSCC undergoing SLNB highlighted 79% sensitivity and 100% specificity, with negative predictive value of 96%.…”

Sentinel nodes: a promise half fulfilled

“…There is now a reported significant improvement in melanoma-specific survival rates to 71 % in those who had sentinel node biopsy, compared to 65 % in those with observation only, although it was noted this difference was reduced in those patients with thicker primary tumours, probably because any advantage of sentinel node biopsy was negated by the high-risk tumour [3]. Therefore we have the possibility that sentinel node biopsy has a therapeutic as well as a diagnostic role and may indeed result not only in improved staging and reduced surgical morbidity but also in improved patient outcomes.…”