Freedom of expression or protectionism in the debate on sentinel node biopsy in melanoma

Abstract

To the Editor: The Organizing Committee of the 6th Biennial International Sentinel Node Society (ISNS) Meeting in Sydney, Australia, held from February 18-20, 2008, refused to allow any presentations from the podium that did not support sentinel node biopsy (SNB) in melanoma. The members of the international panel who prepared the subsequent “consensus statement” all represented the same opinion. All but one of the references cited in the May 2009 commentary by Balch et al1Balch C.M. Morton D.L. Gershenwald J.E. McMasters K.M. Nieweg O.E. Powell B. et al.Sentinel node biopsy and standard of care for melanoma.J Am Acad Dermatol. 2009; 60: 872-875Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar in the Journal were written by the authors themselves. As a result, it is my opinion that both the commentary and the consensus statement are biased. The arguments against SNB in melanoma have recently been published elsewhere2Thomas J.M. Concerns relating to the conduct and statistical analysis of the Multicenter Selective Lymphadenectomy Trial (MSLT-1) in patients with melanoma.J Plast Reconstr Aesthet Surg. 2009; 62: 442-446Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar and will not be repeated here except to comment on the two objections of greatest concern. In the absence of any advantage in overall survival, the calculation of disease-free survival (DFS) in Multicenter Selective Lymphadenectomy Trial (MSLT-1) assumes paramount importance. As calculated by the authors of MSLT-1,3Morton D.L. Thompson J.F. Cochran A.J. Mozzillo N. Elashoff R. Essner R. et al.Sentinel-node biopsy or nodal observation in melanoma.N Engl J Med. 2006; 355: 1307-1317Crossref PubMed Scopus (1461) Google Scholar the improved DFS in the biopsy arm of the study is an inevitable consequence of trial design and does not represent a therapeutic advantage.2Thomas J.M. Concerns relating to the conduct and statistical analysis of the Multicenter Selective Lymphadenectomy Trial (MSLT-1) in patients with melanoma.J Plast Reconstr Aesthet Surg. 2009; 62: 442-446Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar This argument was successfully appealed to the National Cancer Institute (NCI) who funded the MSLT-1. The Clinical Investigations Branch of the NCI issued guidance in 2007 stating that nodal recurrence should be excluded as site of first recurrence in the calculation of DFS in MSLT-1.2Thomas J.M. Concerns relating to the conduct and statistical analysis of the Multicenter Selective Lymphadenectomy Trial (MSLT-1) in patients with melanoma.J Plast Reconstr Aesthet Surg. 2009; 62: 442-446Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Patients with melanoma die of distant metastasis, which is why distant DFS has emerged as the most important secondary endpoint—but the authors of MSLT-1 refuse to address this issue. Both the everyday practice of SNB in melanoma and the results of MSLT-1 assume without proof that all positive sentinel nodes, if not removed, will inevitably progress to palpable nodal recurrence. In their commentary, Balch et al1Balch C.M. Morton D.L. Gershenwald J.E. McMasters K.M. Nieweg O.E. Powell B. et al.Sentinel node biopsy and standard of care for melanoma.J Am Acad Dermatol. 2009; 60: 872-875Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar state that the incidence of nodal recurrence in both arms of MSLT-1 are projected to converge by 10 years. That is unlikely to happen, because between the third interim analysis at 5 years and the fourth interim analysis at 8 years there were only six nodal recurrences in the observation arm and two false-negative recurrences in the biopsy arm,4Morton D.L. Cochran A.J. Thompson J.F. The rationale for sentinel-node biopsy in primary melanoma.Nat Clin Pract Oncol. 2008; 5: 510-511Crossref PubMed Scopus (46) Google Scholar giving a nodal recurrence rate of 16.8% versus 19.6%.2Thomas J.M. Concerns relating to the conduct and statistical analysis of the Multicenter Selective Lymphadenectomy Trial (MSLT-1) in patients with melanoma.J Plast Reconstr Aesthet Surg. 2009; 62: 442-446Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar That equates to an incidence of prognostic false-positivity of 18%.5Thomas J.M. Prognostic false-positivity of the sentinel node in melanoma.Nat Clin Pract Oncol. 2008; 5: 18-23Crossref PubMed Scopus (114) Google Scholar According to the natural history of melanoma, there will be fewer events between the fourth and final analysis, meaning that the curves cannot converge. Prognostic false-positivity is a hypothesis that suggests that a proportion of subcapsular deposits of melanoma in the sentinel node are of no adverse prognostic significance and are destined for dormancy or destruction. Such patients may be given incorrect prognostic information and may undergo unnecessary lymphadenectomy.