Sentinel lymph node biopsy followed by lymph node dissection for localised primary cutaneous melanoma.

BACKGROUND Melanoma is the leading cause of skin cancer-associated mortality. The vast majority of newly diagnosed melanomas are confined to the primary cutaneous site. Surgery represents the mainstay of melanoma treatment. Treatment strategies include wide excision of the primary tumour and sentinel lymph node biopsy (SLNB) to assess the status of the regional nodal basin(s). SLNB has become an important component of initial melanoma management providing accurate disease staging. OBJECTIVES To assess the effects and safety of SLNB followed by completion lymph node dissection (CLND) for the treatment of localised primary cutaneous melanoma. SEARCH METHODS We searched the following databases up to February 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2015, Issue 1), MEDLINE (from 1946), EMBASE (from 1974), and LILACS ((Latin American and Caribbean Health Science Information database, from 1982). We also searched the following from inception: African Index Medicus, IndMED of India, Index Medicus for the South-East Asia Region, and six trials registers. We checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We searched ISI Web of Science Conference Proceedings from inception to February 2015, and we scanned the abstracts of major dermatology and oncology conference proceedings up to 2015. SELECTION CRITERIA Two review authors independently assessed all RCTs comparing SLNB followed by CLND for the treatment of primary localised cutaneous melanoma for inclusion. Primary outcome measures were overall survival and rate of treatment complications and side effects. DATA COLLECTION AND ANALYSIS Two review authors independently extracted and analysed data on survival and recurrence, assessed risk of bias, and collected adverse effect information from included trials. MAIN RESULTS We identified and included a single eligible trial comparing SLNB with observation and published in eight different reports (from 2005 to 2014) with 2001 participants. This did not report on our first primary outcome of overall survival. The study did report on the rate of treatment complications. Our secondary outcomes of disease-specific and disease-free survival, local recurrence and distant metastases were reported. There were 1347 participants in the intermediate-thickness melanoma group and 314 in the thick melanoma group.With regard to treatment complications, short-term surgical morbidity (30 days) in 1735 participants showed no difference between SLNB and observation (risk ratio [RR] 1.11; 95% confidence interval [CI] 0.9 to 1.37) for wide excision of the tumour site but favoured observation for complications related to the regional nodal basin (RR 14.36; 95% CI 6.74 to 30.59).The study did not report the actual 10-year melanoma-specific survival rate for all included participants. Instead, melanoma-specific survival rates for each group of participants: intermediate-thickness melanoma (defined as 1.2 to 3.5 mm) and thick melanomas (defined as 3.50 mm or more) was reported.In the intermediate-thickness melanoma group there was no statistically significant difference in disease-specific survival between study groups at 10 years (81.4 ± 1.5% versus 78.3 ± 2.0%, hazard ratio [HR] 0.84; 95% CI 0.65 to 1.09). In the thick melanoma group, again there was no statistically significant difference in disease-specific survival between study groups at 10 years (58.9.3 ± 4.1% versus 64.4 ± 4.6%, HR 1.12; 95% CI 0.77 to 1.64). Combining these groups there was some heterogeneity (I² = 34%) but the total HR was not statistically significant (HR 0.92; 95% CI 0.74 to 1.14). This study failed to show any difference for its stated primary outcome.The summary estimate for disease-free survival at 10 years favoured SLNB over observation in participants with intermediate-thickness and thick melanomas (HR 0.75; 95% CI 0.63 to 0.89).With regard to the rate of local and regional recurrence as the site of first recurrence, a benefit of SLNB uniformly existed in both groups of participants with intermediate-thickness and thick melanomas (RR 0.56; 95% CI 0.45 to 0.69). This is in contrast with a uniformly unfavourable effect of SLNB with regard to the rate of distant metastases as site of first recurrence, in both groups of participants with intermediate-thickness and thick melanomas (HR 1.33; 95% CI 1.03 to 1.72). AUTHORS' CONCLUSIONS We contacted the trial authors querying the lack of data on overall survival which was the primary outcome of their important study. They stated "there are numerous additional analyses that have yet to be reported for the trial". We expect that overall survival data will be available in a future update of this review.Disease-free survival and rate of local and regional recurrence favoured SLNB in both groups of participants with intermediate-thickness and thick melanomas but short-term surgical morbidity was higher in the SLNB group, especially with regard to complications in the nodal basin.The evidence for the outcomes of interest in this review is of low quality due to the risk of bias and imprecision of the estimated effects. Further research may have an important impact on our estimate of the effectiveness of SLNB in managing primary localised cutaneous melanoma. Currently this evidence is not sufficient to document a benefit of SLNB when compared to observation in individuals with primary localised cutaneous melanoma.