The Prognostic Value of Minimally Involved Melanoma Sentinel Lymph Nodes

Abstract

Background: Sentinel node (SLN) status is the most important prognostic factor for early-stage melanoma patients. It will influence follow-up and may change therapy. Positive SLNs present different degrees of involvement so that subgroups of patients may have minimal SLN invasion. The aim of this study was to evaluate survival in subgroups with minimally involved SLNs and to compare them to negative SLN patients. Method: SLN biopsy was performed in 499 consecutive clinically N0 patients between 1997 and 2008. Following updated recommendations from the Melanoma Group of the European Organization of Research and Treatment of Cancer, degrees of SLN involvement were fully reassessed for two anatomopathological parameters: tumour burden according to Rotterdam criteria (<0.1 mm, 0.1 - 1.0 mm, and >1.0 mm) and microanatomic location according to Dewar (subcapsular, combined subcapsular and parenchymal, parenchymal, multifocal, or extensive). Minimally involved SLNs were defined as those with tumor burden <0.1 mm and/or subcapsular metastasis location. Kaplan-Meier and multivariable logistic regression analyses were performed. Results: Out of 499 clinically N0 patients, positive SLNs were found in 123 patients (24.7 percent). With a median follow-up of 52 months (range: 9 - 146), five-year disease-free (DFS), disease-specific survival (DSS) and overall survival (OS) were 88.1, 93.9 and 89.9 percent for negative SLN patients, respectively. In minimally involved SLNs, there were 21 with tumour burden <0.1 mm, and 52 with subcapsular metastasis. Five-year DFS, DSS and OS in these sub-groups were 79.6, 86.6 and 86.6 percent, then 57.3, 69.8 and 67.8 percent respectively. DFS univariable analysis of these sub-groups compared to negative SLNs showed: (HR1.89, 95 percent CI 0.75 - 4.79; p 0.175) and (HR 3.92, 95 percent CI 2.29 - 6.71; p < 0.0001) respectively. Minimally involved sub-groups were not predictive for NSLN negativity. Conclusion: Rotterdam’s tumour burden stratification is an easy and useful prognostic factor of melanoma survival. There was a trend showing that patients with SLN tumour burden <0.1 mm have a lower survival compared to SLN negative patients. One might suggest that patients with minimally involved SLNs may not be managed similarly to negative SLN patients. Subcapsular metastasis subgroup according to the microanatomic location has statistically significant worst survival.

Share and Cite:

A. Saadi, D. Roulin, E. Saiji, H. Bouzourene, N. Demartines and M. Matter, "The Prognostic Value of Minimally Involved Melanoma Sentinel Lymph Nodes," Journal of Cancer Therapy, Vol. 4 No. 10, 2013, pp. 1490-1498. doi: 10.4236/jct.2013.410180.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] D. L. Morton, D. R. Wen, J. H. Wong, J. S. Economou, L. A. Cagle, F. K. Storm, L. J. Foshag and A. J. Cochran, “Technical Details of Intraoperative Lymphatic Mapping for Early Stage Melanoma,” Archives of Surgery, Vol. 127, No. 4, 1992, pp. 392-399. http://dx.doi.org/10.1001/archsurg.1992.0142 0040034005
[2] T. M. Johnson, V. K. Sondak, C. K. Bichakjian and M. S. Sabel, “The Role of Sentinel Lymph Node Biopsy for Melanoma: Evidence Assessment,” Journal of the American Academy of Dermatology, Vol. 54, No. 1, 2006, pp. 19-27. http://dx.doi.org/10.1016/j.jaad.2005.09.029
[3] D. Roulin, M. Matter, P. Bady, D. Lienard, O. Gugerli, A. Boubaker, L. Bron and F. J. Lejeune, “Prognostic Value of Sentinel Node Biopsy in 327 Prospective Melanoma Patients from a Single Institution,” European Journal of Surgical Oncology, Vol. 34, No. 6, 2008, pp. 673-679.
http://dx.doi.org/10.1016/j.ejso.2007.07.197
[4] M. G. Cook, M. A. Green, B. Anderson, A. M. Eggermont, D. J. Ruiter, A. Spatz, M. W. Kissin and B. W. Powell, “The Development of Optimal Pathological Assessment of Sentinel Lymph Nodes for Melanoma,” The Journal of Pathology, Vol. 200, No. 3, 2003, pp. 314-319. http://dx.doi.org/10. 1002/path.1365
[5] D. J. Dewar, B. Newell, M. A. Green, A. P. Topping, B. W. Powell and M. G. Cook, “The Microanatomic Location of Metastatic Melanoma in Sentinel Lymph Nodes Predicts Nonsentinel Lymph Node Involvement,” Journal of Clinical Oncology, Vol. 22, No. 16, 2004, pp. 3345-3349.
http://dx.doi.org/10.1200/JCO.2004.12.177
[6] D. L. Morton, J. F. Thompson, A. J. Cochran, N. Mozzillo, R. Elashoff, R. Essner, O. E. Nieweg, D. F. Roses, H. J. Hoekstra, C. P. Karakousis, D. S. Reintgen, B. J. Coventry, E. C. Glass and H. J. Wang, “Sentinel-Node Biopsy or Nodal Observation in Melanoma,” The New England Journal of Medicine, Vol. 355, No. 13, 2006, pp. 1307-1317. http://dx.doi.org/10.1056/NEJMoa060992
[7] A. C. van Akkooi, Z. I. Nowecki, C. Voit, G. SchaferHesterberg, W. Michej, J. H. de Wilt, P. Rutkowski, C. Verhoef and A. M. Eggermont, “Sentinel Node Tumour Burden According to the Rotterdam Criteria Is the Most Important Prognostic Factor for Survival in Melanoma Patients: A Multicenter Study in 388 Patients with Positive Sentinel Nodes,” Annals of Surgery, Vol. 248, No. 6, 2008, pp. 949-955.
[8] A. P. van der Ploeg, A. C. van Akkooi, P. I .Schmitz, S. Koljenovic, C. Verhoef and A. M. Eggermont, “EORTC Melanoma Group Sentinel Node Protocol Identifies High Rate of Submicrometastases According to Rotterdam Criteria,” European Journal of Cancer, Vol. 46, No. 13, 2010, pp. 2414-2421. http://dx.doi.org/10.1016/j.ejca.2010.06.003
[9] A. P. van der Ploeg, A. C. van Akkooi, P. Rutkowski, Z. I. Nowecki, W. Michej, A. Mitra, J. A. Newton-Bishop, M. Cook, I. M. van der Ploeg, O. E. Nieweg, M. F. van den Hout, P. A. van Leeuwen, C. A. Voit, F. Cataldo, A. Testori, C. Robert, H. J. Hoekstra, C. Verhoef, A. Spatz and A. M. Eggermont, “Prognosis in Patients with Sentinel Node-Positive Melanoma Is Accurately Defined by the Combined Rotterdam Tumor Load and Dewar Topography Criteria,” Journal of Clinical Oncology, Vol. 29, No. 16, 2011, pp. 2206-2214. http://dx.doi.org/10.1200/JCO.2010.31.6760
[10] A. P. van der Ploeg, A. C. van Akkooi, L. E. Haydu, R. A. Scolyer, R. Murali, C. Verhoef, J. F. Thompson and A. M. Eggermont, “The Prognostic Significance of Sentinel Node Tumour Burden in Melanoma Patients: An International, Multicenter Study of 1539 Sentinel NodePositive Melanoma Patients,” European Journal of Cancer, 2013, Article in press.
[11] D. L. Morton, A. J. Cochran, J. F. Thompson, R. Elashoff, R. Essner, E. C. Glass, N. Mozzillo, O. E. Nieweg, D. F. Roses, H. J. Hoekstra, C. P. Karakousis, D. S. Reintgen, B. J. Coventry and H. J. Wang, “Sentinel Node Biopsy for Early-Stage Melanoma: Accuracy and Morbidity in MSLT-I, an International Multicenter Trial,” Annals of surgery, Vol. 242, No. 3, 2005, pp. 302-311.
[12] J. E. Gershenwald, R. H. Andtbacka, V. G. Prieto, M. M. Johnson, A. H. Diwan, J. E. Lee, P. F. Mansfield, J. N. Cormier, C. W. Schacherer and M. I. Ross, “Microscopic Tumour Burden in Sentinel Lymph Nodes Predicts Synchronous Nonsentinel Lymph Node Involvement in Patients with Melanoma,” Journal of Clinical Oncology, Vol. 26, No. 26, 2008, pp. 4296-4303. http://dx.doi.org/10.1200/JCO.2007.15.4179
[13] A. Govindarajan, D. M. Ghazarian, D. R. McCready and W. L. Leong, “Histological Features of Melanoma Sentinel Lymph Node Metastases Associated with Status of the Completion Lymphadenectomy and Rate of Subsequent Relapse,” Annals of Surgical Oncology, Vol. 14, No. 2, 2007, pp. 906-912. http://dx.doi.org/10.1245/s10434-006-9241-3
[14] M. E. Reeves, R. Delgado, K. J. Busam, M. S. Brady and D. G. Coit, “Prediction of Nonsentinel Lymph Node Status in Melanoma,” Annals of Surgical Oncology, Vol. 11, No. 1, 2003, pp. 27-31.
http://dx.doi.org/10.1245/ASO.2003.03.020
[15] R. P. Scheri, R. Essner, R. R. Turner, X. Ye and D. L. Morton, “Isolated Tumour Cells in the Sentinel Node Affect Long-Term Prognosis of Patients with Melanoma,” Annals of Surgical Oncology, Vol. 14, No. 10, 2007, pp. 2861-2866. http://dx.doi.org/10.1245/s10434-007-9472-y
[16] H. Starz, K. Siedlecki and B. R. Balda, “Sentinel Lymphonodectomy and s-Classification: A Successful Strategy for Better Prediction and Improvement of Outcome of Melanoma,” Annals of Surgical Oncology, Vol. 11, No. 3, 2004, pp. 162S-168S.
[17] T. Francischetto, N. Spector, J. F. Neto Rezende, M. de Azevedo Antunes, S. de Oliveira Romano, I. A. Small and C. Gil Ferreira, “Influence of Sentinel Lymph Node Tumor Burden on Survival in Melanoma,” Annals of Surgical Oncology, Vol. 17, No. 4, 2010, pp. 1152-1158. http://dx.doi.org/10.1245/s10434-009-0884-8
[18] A. C. van Akkooi, A. Spatz, A. M. Eggermont, M. Mihm and M. G. Cook, “Expert Opinion in Melanoma: The Sentinel Node; EORTC Melanoma Group Recommendations on Practical Methodology of the Measurement of the Microanatomic Location of Metastases and Metastatic Tumour Burden,” European Journal of Cancer, Vol. 45, No. 16, 2009, pp. 2736-2742. http://dx.doi.org/10.1016/ j.ejca.2009.08.015
[19] D. L. Morton, L. Wanek, J. A. Nizze, R. M. Elashoff and J. H. Wong, “Improved Long-Term Survival after Lymphadenectomy of Melanoma Metastatic to Regional Nodes. Analysis of Prognostic factors in 1134 Patients from the John Wayne Cancer Clinic,” Annals of Surgery, Vol. 214, No. 4, 1991, pp. 491-499. http://dx.doi.org/10.1097/00000658-199110000-00013
[20] A. J. Cochran, D. R. Wen, R. R. Huang, H. J. Wang, R. Elashoff and D. L. Morton, “Prediction of Metastatic Melanoma in Nonsentinel Nodes and Clinical Outcome Based on the Primary Melanoma and the Sentinel Node,” Modern Pathology, Vol. 17, No. 7, 2004, pp. 747-755. http://dx.doi.org/10. 1038/modpathol.3800117
[21] S. Debarbieux, G. Duru, S. Dalle, O. Beatrix, B. Balme and L. Thomas, “Sentinel Lymph Node Biopsy in Melanoma: A Micromorphometric Study Relating to Prognosis and Completion Lymph Node Dissection,” The British Journal of Dermatology, Vol. 157, No. 1, 2007, pp. 58-67.
http://dx.doi.org/10.1111/j.1365-2133.2007.07937.x
[22] A. C. van Akkooi, J. H. de Wilt, C. Verhoef, P. I. Schmitz, A. N. van Geel, A. M. Eggermont and M. Kliffen, “Clinical Relevance of Melanoma Micrometastases (<0.1 mm) in Sentinel Nodes: Are These Nodes to be Considered Negative?” Annals of Oncology, Vol. 17, No. 10, 2006, pp. 1578-1585. http://dx.doi.org/10.1093/annonc/mdl176
[23] A. P. van der Ploeg, A. C. van Akkooi, P. Rutkowski, M. Cook, O. E. Nieweg, C. R. Rossi, A. Testori, S. Suciu, C. Verhoef, A. M. Eggermont, European Organization for Research and Treatment of Cancer Melanoma Group, “Prognosis in Patients with Sentinel Node-Positive Melanoma without Immediate Completion Lymph Node Dissection,” British Journal of Surgery, Vol. 99, No. 10, 2012, pp. 1396-1405. http://dx.doi.org/10.1002/bjs.8878
[24] C. Garbe, K. Peris, A. Hauschild, P. Saiag, M. Middleton, A. Spatz, J. J. Grob, J. Malvehy, J. Newton-Bishop, A. Stratigos, H. Pehamberger, A. M. Eggermont, European Dermatology Forum, European Association of Dermato-Oncology, European Organization of Research and Treatment of Cancer, “Diagnosis and Treatment of Melanoma. European Consensus-Based Interdisciplinary Guideline —Update 2012,” European Journal of Cancer, Vol. 48, No. 15, 2012, pp. 2375-2390.
http://dx.doi.org/10.1016/j.ejca.2012.06.013

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.