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LETTERS: J Meirion Thomas and Matthew A Clark Sentinel lymph node biopsy: Not yet standard of care for melanoma BMJ 2004; 329: 170 [Full text]

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Sentinel lymph-node biopsy in malignant melanoma

Robin Russell-Jones, Ciaran Healy, Ann-Marie Powell, Katharine Acland, Michael O'Doherty, Eduardo Calonje   (24 August 2004)

Informed Consent and Sentinel Node Biopsy in Melanoma

Juan Manuel Marquez   (15 January 2007)

Sentinel lymph-node biopsy in malignant melanoma 24 August 2004
Robin Russell-Jones, Director Skin Tumour Unit St Thomas Hospital London SE1 7EH, Ciaran Healy, Ann-Marie Powell, Katharine Acland, Michael O'Doherty, Eduardo Calonje Send response to journal: Re: Sentinel lymph-node biopsy in malignant melanoma	The arguments put forward by Thomas and colleagues (1) against the use of sentinel node biopsy in malignant melanoma have not changed over the past 4 years (2). However there is data now available that allows us to test the hypothesis that completion lymphadenectomy might increase the rate of intransit disease. We have identified 10 studies, including our own which report patterns of relapse separately according to sentinel node status (3).Overall there were 701 relapses amongst 4713 subjects of which 94 were nodal, 201 were either intransit or local recurrence, and 406 were distant, giving an absolute rate of 2, 4.3 and 8.8% respectively. In cohorts not subjected to selective lymphadenectomy the equivalent figures are 7.8% nodal, 3.4% intransit and 4.4% distant (4). In other words selective lymphadenectomy reduces the absolute rate of nodal relapse mainly at the expense of an increased rate of distant metastases. It is difficult to attach too much significance to the modest increase in the rate of intransit disease as the cohorts subjected to selective lymphadenectomy commonly excluded patients with Stage 1A disease, whereas the historical cohort was unselected. As expected the overall relapse rate amongst node positive subjects was almost 3 times the node negative cohorts (11.6 versus 31%), but it is also instructive to compare patterns of relapse according to sentinel node status. Amongst sentinel node negative subjects, 16% of all relapses were nodal, 53% were distant, and 31% were intransit. Amongst sentinel node positive cohorts 8% were nodal, 59% were distant and 33% were intransit.This small difference for intransit disease is not significant, and does not support the hypothesis that completion lymphadenectomy increases the likelihood of intransit disease. We would also take issue with the statement that adjuvant therapy with Interferon confers no survival benefit. The meta-analysis quoted by Thomas and Clark shows an unequivocal and dose-related improvement for disease- free survival( p<0.000003) and, if the analysis is confined to the high -dose studies, a marginal benefit for overall survival (p=0.05) (5) The fact that the NHS is not prepared to fund this therapy owes more to cost than toxicity. Yours Sincerely Robin Russell-Jones, director Skin Tumour Unit, St John's Institute of Dermatology, Ciaran Healy, Consultant plastic surgeon, department of plastic surgery, Ann-Marie Powell, SpR, Skin Tumour Unit, Katharine Acland, consultant dermatologist, Skin Tumour Unit, Michael O'Doherty. consultant nuclear physician, department of nuclear medicine Eduardo Calonje, director diagnostic dermatopathology, St John's Institute of Dermatology, St Thomas Hospital. London SE1 7EH. Refs 1. Meiron Thomas J, Clark M Not yet standard of care for melanoma(letter) BMJ 2004; 329: 170 2. Meiron Thomas J, Patocskai E. The argument against sentinel node biopsy for malignant melanoma (editorial) BMJ 2000; 321: 3-4. 3. A.M. Powell, E Calonje, K Acland, C Healy, M Doherty, T Grunewald, R Russell-Jones (2004) Pattern of clinical recurrence in patients with malignant melanoma and negative sentinel node biopsies Brit J Dermatol 151 (Suppl 68): 82-3. 4. Meier F, Will S, Ellwanger U et al. Metastatic pathways and time courses in the orderly progression of cutaneous melanoma. Br J Dermatol. 2002 ;147:62-70 5. Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S. Does adjuvant interferon-alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev 2003; 29:241-52. Competing Interests: None. Competing interests: None declared
Informed Consent and Sentinel Node Biopsy in Melanoma 15 January 2007
Juan Manuel Marquez, Plastic surgeon Hospital Clinico Universitario. Avda. Vicente Blasco Ibañez, 17. Valencia 46010. Spain Send response to journal: Re: Informed Consent and Sentinel Node Biopsy in Melanoma	EDITOR - For years we have been looking forward to the results of the Multicenter Selective Lymphadenectomy Trial (MSLT). In this trial, patients with primary cutaneous melanomas were randomly assigned to wide excision and observation or to wide excision plus sentinel node biopsy, with completed lymphadenectomy if node involvement. This was expected to provide more definite answers on survival and long-term safety of sentinel node biopsy in melanoma. And it has been considered that the final decision for or against sentinel lymph node biopsy in melanoma should await the result of it.(Reference 1) The primary end point of the third interim analysis of the MSLT, published last September,(Reference 2) is that 5-year overall survival is similar in the two groups. The second most significant end point is that 5-year disease-free survival is higher in the biopsy group. However, if we consider sites of first recurrences (from data of this trial in Baseline Characteristics of the Patients) we observe that the incidence of distant recurrences is higher in the biopsy group than in the observation group (11% versus 7.8%, respectively); which implies that 5-year distant disease-free survival is higher in the observation group. The significance of this is such that the European Organization for Research and Treatment of cancer has adopted distant disease-free survival as a surrogate for overall survival. So, as previously reported,(Reference 3) sentinel lymphadenectomy has reduced the rate of nodal relapse but increased the rate of distant metastases. Patients with melanoma should be reported in the informed consent that sentinel lymph node biopsy is still an investigational procedure(Reference 1) that has not shown to improve overall survival, nor to protect patients from melanoma-related death caused by distant metastases.(Reference 4) Beside, informed consent should also consider the implications of a possible increase in the rate of these worst prognostic recurrences. Furthermore, parents deserve to know that, although the most important trial of sentinel node biopsy for melanoma has concluded that this procedure provides important prognostic information,(Reference 2) its prognostic value in the younger is uncertain.(Reference 5) And so it will remain, unless they are entered into further clinical trials; as neither children nor adolescents were entered into this one. REFERENCES 1. Meiron Thomas J, Clark M. Sentinel lymph node biopsy. BMJ 2004; 329:170. 2. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 2006; 355:1307-17 3. Russell-Jones R, Healy C, Powell AM, Acland K, O´Doherty M, Calonje E. Completion Lymphadenectomy may not increase in-transit disease in malignant melanoma. BMJ 2004; 329: 1288-1289. 4. Gutzmer R, Al Ghazal M, Geerlings H, Kapp A. Sentinel node biopsy in melanoma delays recurrence but does not change melanoma-related survival: a retrospective analysis of 673 patients. Br J Dermatol 2005; 153 (6): 1137-41 5. Roaten JB, Partrick DA, Bensard D, Pearlman N, Gonzalez R, Fitzpatrick J, et al. Survival in sentinel lymph node-positive pediatric melanoma. J pediatr Surg 2005; 40 (6): 988-92 Competing interests: None declared