Who Is to Blame for False-Negative Sentinel Node Biopsies in Melanoma?

No matter how one defines standard of care, sentinel lymph node biopsy (SLNB) has become standard of care for the treatment of clinically localized melanoma.1,2 Given this fact, it is surprising that more attention has not been paid to the issue of false-negative results of sentinel node biopsy. In the current issue of Annals of Surgical Oncology, Scoggins et al. report on the false-negative rate of sentinel node biopsy from a large series of patients entered prospectively into the multi-institutional Sunbelt Melanoma Trial.3 An important starting point for any discussion of this topic is how to define and report the false-negative rate. Some investigators have reported the number of false-negative sentinel node biopsies (generally defined as any first recurrence of melanoma in a lymph node potentially draining the primary tumor) occurring out of all procedures performed. This is an incorrect representation of the false-negative rate and not a relevant number to patients and surgeons. In contrast, a very important number is the ratio of true-negative biopsies to all negative biopsies (false negatives plus true negatives). This is the negative predictive value of the sentinel node biopsy procedure and is of great value to surgeons when they counsel patients after a negative sentinel node biopsy procedure, but it is still not the false-negative rate. The negative predictive value of sentinel node biopsy in large series has been reported between 94 and 98.5% (Table 1), meaning that only 2–6 patients per 100 who are told their nodes are negative are given that information incorrectly. However, the actual definition of the false-negative rate is the ratio of false-negative results to the total number of positive lymph nodes (false negatives plus true positives). This value has been reported in the range 6–21%. Importantly, any method of reporting on the likelihood that a truly positive lymph node will be missed by the sentinel node procedure depends on the a priori likelihood that any lymph nodes are actually involved by melanoma. Put another way, if all the lymph nodes in a patient are uninvolved by tumor, it does not matter which nodes the surgeon removes—the result will be a true negative. The corollary of this, however, is that patients whose melanoma is most likely to have spread to the regional nodes are those most likely to have a false-negative sentinel node biopsy. It also follows that different series of patients undergoing sentinel node biopsy using identical techniques (and with identical accuracy) will report different false-negative rates and negative predictive values if the baseline characteristics of the melanoma patients differ. In addition, because nodal recurrences can take many years to manifest clinically, as the duration of follow-up increases, the false-negative rate and total positive node percentage will increase. In the Sunbelt Melanoma Trial data reported by Scoggins et al., after median follow-up of 61 months, the overall likelihood of a positive lymph node was 19.8% (486/2,451), the negative predictive value of a sentinel node biopsy was 97.0% (1,906/59 + 1,906), and the false-negative rate was 10.8% (59/59 + 486).3 The corresponding values in other contemporary large series of melanoma patients undergoing sentinel node biopsy are shown in Table 1.