VIEWPOINT 604 REPRINTED FROM AFP VOL.44, NO.8, AUGUST 2015 © The Royal Australian College of General practitioners 2015 Andrew Spillane, Rebecca Read, John Thompson Sentinel node biopsy should be the standard of care for patients with intermediate and thick melanomas entinel node biopsy (SNB) has been widely accepted by surgical and medical oncologists to be the standard of care for patients with intermediate and thick melanomas. It can also be considered and discussed in patients with high-risk thin melanomas. This was reflected in an international consensus statement published in 2012. 1 SNB has also been promoted in the National Health and Medical Research Council (NHMRC) guidelines since 2008, which recommend it be discussed with patients with intermediate and thick melanomas. 2 The opinions expressed in a viewpoint article by Dixon et al in July 2014 diverged from this consensus statement and the common practice in oncology centres. 1,3 The Multicenter Selective Lymphadenectomy Trial (MSLT-1) provides the highest level of evidence for evaluating SNB in melanoma patients. 4 The trial involved 2001 patients who were randomised to have either SNB and completion lymphadenectomy if the SNB was positive, or observation only and delayed lymphadenectomy if there was lymph node relapse. Around 16% of patients with intermediate thickness melanoma (Breslow thickness 1.2–3.5 mm) were SNB-positive. However, 4% of patients had a falsely negative SNB result and tumours recurred later in the lymph nodes, despite the earlier negative SNB. Around 20% of patients in the observation group had lymph node relapses (Figure 1A). 4 Around 41% of patients with thick melanomas (Breslow thickness >3.5 mm) in both groups had involved lymph nodes (Figure 1B). 4 The similar frequencies of lymph node involvement is strong supporting evidence for the validity of comparing the two groups of lymph node-positive patients in intermediate and thick melanoma patients. SNB is a diagnostic procedure that aims to identify involved lymph nodes earlier than clinical or radiological assessments. Clearly, removing a nodal metastasis earlier can only possibly improve survival in patients with lymph node metastasis present. There was no significant difference in melanoma-specific survival (MSS) between the two randomised groups in MSLT-1 (Figure 1C, D). 4 Given that only 16% of patients who were SNB-positive could have had an impact on the survival of that group (if there were a benefit), and the event rate was lower than expected, the study was underpowered to detect a small difference (if it existed). Although patients who have no lymph node involvement cannot benefit from SNB in terms of survival, they do benefit from more accurate prognostic information. In terms of MSS, the most important comparator groups in MSLT-1 were the SNB-positive patients and the (roughly) same proportion of patients who developed palpable lymph node metastases during observation. Clearly these groups could not be randomised, but the New England Journal of Medicine has accepted comparing their outcomes using previously validated statistical methodology. 4,5 Since publication of the final MSLT-1 results, most melanoma specialists in oncology centres continue to recommend that SNB remain the standard of care in patients with intermediate and thick melanomas and be considered in those with high-risk thin melanomas because: 1 1. MSS was improved in SNB-positive patients with intermediate-thickness melanomas who had an immediate completion lymphadenectomy when compared with those who subsequently developed clinically involved lymph nodes and underwent delayed lymphadenectomy (Figure 1C). MSS at 10 years improved from 41.5% to 62.1%. 2. Sentinel node status is the strongest prognostic factor for MSS, as shown in multiple large studies, including MSLT-1. It is now also known that factors relating to the degree of sentinel node involvement can further stratify 10-year MSS in a range from <40% to >90%. 6 3. SNB identifies patients with lymph node involvement early (Figure 1A, B), 4 with the exception of false-negative cases. Patients who have a false- negative result (2–4% of all SNB cases) 4 have a similar prognosis as those not undergoing SNB who later present with lymph node involvement (Figure 1C, D). 4 Minimising false-negative SNBs is an important, ongoing process. S