Sentinel lymph node biopsy for melanoma: a plea to let the data be heard.

Abstract

In his companion editorial, Dr. Coit lauds the final analysis of the first Multicenter Selective Lymphadenectomy Trial (MSLT-I), reported recently in the New England Journal of Medicine, saying that it ‘‘has provided clinicians with invaluable very high quality information to interpret and use in the management of their melanoma patients’’. However, he expresses concern about ‘‘how the authors have presented this information to the readers’’. The planning and conduct of MSLT-1 was a mammoth project, and the fact that the final report was not publishable until 20 years after the first of the 2001 trial patients was randomized highlights not only the scale of the undertaking but also the dedication and commitment of clinicians, trial personnel, and patients around the world to its successful completion, when 10 years of follow-up had been achieved for all trial participants. The mass of data collected in MSLT-I over the 20-year period was large, making it impossible to report and discuss all the results in a single journal publication. However, we can reassure Dr. Coit and others that hitherto unreported trial data will be presented in subsequent publications. The broad statement by Dr. Coit that ‘‘this is a negative trial’’ refers only to the primary endpoint—improvement in melanoma-specific survival. This sweeping claim ignores the multiple statistically significant benefits that were demonstrated for critically important, predetermined secondary endpoints, notably a significant improvement in disease-free survival in the sentinel lymph node biopsy (SLNB) group and significantly improved melanoma-specific survival in sentinel lymph node (SLN)-positive patients treated by immediate completion lymph node dissection (CLND). In relation to melanoma-specific survival, the results of MSLT-I are consistent with those of previous randomized trials of elective lymph node dissection (ELND), and Dr. Coit concedes this. Although these previous trials were insufficiently powered (as was MSLT-1) to demonstrate an overall survival benefit for patients undergoing ELND (or SLNB/CLND), they consistently demonstrated a likely survival benefit for the cohort of patients with intermediate-thickness melanomas. In addition, although neither MSLT-I nor the earlier ELND trials showed a statistically significant improvement in overall melanoma-specific survival following early nodal surgery, they demonstrated a consistent advantage that falls short of statistical significance. Lack of statistical significance in an underpowered trial should not be interpreted as a demonstration of equality. For patients with thick melanomas, Dr. Coit accepts that MSLT-I data (Fig. 3b) support the concept that finding melanoma cells in an SLN predicts the eventual development of clinically detectable nodal disease (if the SLN is not removed). However, he is unwilling to accept that the same is true for patients with intermediate thickness melanomas because the incidence of ‘positive’ nodes after 10 years is 2.4 % higher after SLN biopsy and follow-up than after observation alone. He suggests that the curves in Fig. 3a are ‘‘remarkably parallel’’ beyond 5–6 years follow-up. This is not true. As we have previously indicated, over 25 % of the numerical difference between the curves reporting cumulative incidence of nodal metastasis vanishes between 8 and 10 years of follow-up. Formal followup of MSLT-1 patients did not extend beyond 10 years, but Society of Surgical Oncology 2014