Abstract: We identified and included a single eligible trial comparing SLNB with observation which was published in eight different reports (from 2005 to 2014) with 2001 participants. This trial did not report on our first primary outcome of overall survival (which was also the planned primary outcome of this trial). When contacted for this important data, the trial authors stated "there are numerous additional analyses that have yet to be reported for the trial". We were able however to estimate overall survival from data included in the appendix of the published report and found no evidence of benefit for SLNB for overall survival. The overall survival hazard ratio (HR) using ITT (intention-to-treat) analysis was 0.99 95% confidence interval [CI] 0.82 to 1.19, 1661 participants). The overall survival using ITT for intermediate thickness melanomas was (HR 0.92, 95% CI 0.73 to 1.16) and for thick melanomas it was (HR 1.15, 95% CI 0.82 to 1.61). The study did report on our second primary outcome of rate of treatment complications: short-term surgical morbidity (30 days) in 1735 participants showed no difference between SLNB and observation (risk ratio [RR] 1.11, 955 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). 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.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%, 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). 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). We found no evidence of improved overall survival or melanoma-specific survival rates for participants with intermediate or thick melanomas who underwent SLNB compared with observation alone. 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.

Plain-language summary: We found one published randomised controlled trial with 2001 participants with localised skin cancer who had undergone removal of the primary tumour and were then randomised to receive SLNB or observation. Participants testing positive for cancer cells in the sentinel lymph node then underwent CLND. Participants in the observation group underwent removal of the lymph nodes only on disease recurrence. The study did not report on our primary outcome of interest (overall survival), but it did report on our secondary outcomes of disease-specific survival (time to death only from melanoma), disease-free survival (time to first melanoma recurrence at any site), and recurrence. Although the authors of the one included study did not report the primary outcome of overall survival, we were able to calculate it from data they included in their report appendix which showed no benefit of SLNB for people with intermediate or thick melanomas. Our one included study also did not report any difference in disease-specific survival for participants who underwent SLNB or observation. Disease-free survival was better in the SLNB treatment group. However, recurrence of the melanoma at a distant site in the body occurred more frequently in participants in the SLNB group than in those in the observation group. We assessed the quality of the evidence for this trial as low for the above outcomes. As indicated by the results of this one included study, there is no clear evidence at present to recommend that SLNB, followed by CLND. is a better means of improving overall or melanoma-specific survival than observation.