In Surgical Treatment of Non-Small-Cell Lung Cancer a Minimum Number of Resected Mediastinal Lymph Nodes Is Mandatory for Accurate Staging

Armin Kolb^*, Elena Steidele, Craig Matthews, Johannes Merk, Karl-Heinz Orend, Bernd Mühling

Department of Cardiothoracic and Vascular Surgery, University of Ulm, Ulm, Germany.

DOI: 10.4236/ss.2014.510072                

Abstract

Objective: Increased numbers of removed lymph nodes (LN) are resulting in more accurate staging of the patient (Will-Rogers-Phenomenon). This study evaluates dependence of lymph node sample size to 1) Will-Rogers-Phenomenom, 2) influence of sample size on overall survival and in terms of 3) morbidity and mortality. Methods: 131 patients after pulmonary resection were retrospectively analysed concerning surgery, number of removed lymph nodes, stage, complications and survival. Patients were stratified according to the median number of lymph nodes in two groups (A <12 lymph nodes and B ≥12 lymph nodes). Results: 5% of the patients had only local lymphadenectomy and in 14% a systematic lymphadenectomy was performed. 17% of the patients showed skip metastasis. Lymph node positivity was correlated to the number of removed lymph nodes (p = 0.003). The approximated median survival for UICC (Union internationale contre le cancer) stage I was 511, stage II 521 and stage III 290 days. Subgroup analysis of survival data showed in group A an approximated median survival at stage I of 495 days, at II 537 days and at III 451.5 days. Group B showed at stage I 675 days, at II 521 days and at III 221 days. There was no difference in complications and mortality. Conclusion: A too low sample size leads to understaging due to skip metastasis. Obligatory mediastinal lymph node sampling would decrease the risk of understaging due to skip metastasis and does not increase morbidity or complications. Lymph node sampling is not inferior concerning morbidity and survival in our patient collective. This study cannot recommend a minimum number of LN to be resected. The evaluated limit of 12 LN proves to be suitable as a guideline.

Keywords

Lung Cancer Surgery, Lymph Node, Lymphadenectomy, Lymph Node Sampling, Systematic Lymphadenectomy, Nsclc, Non-Small-Cell Lung Cancer

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Siegel, R., DeSantis, C., Virgo, K., Stein, K., Mariotto, A., Smith, T., Cooper, D., Gansler, T., Lerro, C., Fedewa, S., Lin, C., Leach, C., Cannady, R.S., Cho, H., Scoppa, S., Hachey, M., Kirch, R., Jemal, A. and Ward, E. (2012) Cancer treatment and survivorship statistics, 2012. CA: A Cancer Journal for Clinicians, 62, 220-241. http://dx.doi.org/10.3322/caac.21149
[2]	Spira, A. and Ettinger, D.S. (2004) Multidisciplinary Management of Lung Cancer. The New England Journal of Medicine, 350, 379-392. http://dx.doi.org/10.1056/NEJMra035536
[3]	Muehling, B., Wehrmann, C., Oberhuber, A., Schelzig, H., Barth, T. and Orend, K.H. (2012) Comparison of Clinical and Surgical-Pathological Staging in IIIA Non-Small Cell Lung Cancer Patients. Annals of Surgical Oncology, 19, 89-93. http://dx.doi.org/10.1245/s10434-011-1895-9
[4]	Cetinkaya, E., Turna, A., Yildiz, P., Dodurgali, R., Bedirhan, M.A., Gurses, A. and Yilmaz, V. (2002) Comparison of Clinical and Surgical-Pathologic Staging of the Patients with Non-Small Cell Lung Carcinoma. European Journal Cardio-Thoracic Surgery, 22, 1000-1005. http://dx.doi.org/10.1016/S1010-7940(02)00581-X
[5]	Lopez-Encuentra, A., Garcia-Lujan, R., Rivas, J.J., Rodriguez-Rodriguez, J., Torres-Lanza, J. and Varela-Simo, G. (2005) Comparison between Clinical and Pathologic Staging in 2,994 Cases of Lung Cancer. The Annals of Thoracic Surgery, 79, 974-979; discussion 979. http://dx.doi.org/10.1016/j.athoracsur.2004.06.004
[6]	Cerfolio, R.J., Ojha, B., Bryant, A.S., Raghuveer, V., Mountz, J.M. and Bartolucci, A.A. (2004) The Accuracy of Integrated PET-CT Compared with Dedicated Pet Alone for the Staging of Patients with Nonsmall Cell Lung Cancer. The Annals of Thoracic Surgery, 78, 1017-1023. http://dx.doi.org/10.1016/j.athoracsur.2004.02.067
[7]	Lardinois, D., Weder, W., Hany, T.F., Kamel, E.M., Korom, S., Seifert, B., von Schulthess, G.K. and Steinert, H.C. (2003) Staging of Non-Small-Cell Lung Cancer with Integrated Positron-Emission Tomography and Computed Tomography. The New England Journal of Medicine, 348, 2500-2507. http://dx.doi.org/10.1056/NEJMoa022136
[8]	Gonzalez-Stawinski, G.V., Lemaire, A., Merchant, F., O’Halloran, E., Coleman, R.E., Harpole, D.H. and D’Amico, T.A. (2003) A Comparative Analysis of Positron Emission Tomography and Mediastinoscopy in Staging Non-Small Cell Lung Cancer. The Journal of Thoracic and Cardiovascular Surgery, 126, 1900-1905. http://dx.doi.org/10.1016/S0022-5223(03)01036-5
[9]	Tournoy, K.G., Maddens, S., Gosselin, R., Van Maele, G., van Meerbeeck, J.P. and Kelles, A. (2007) Integrated FDGPET/CT Does Not Make Invasive Staging of the Intrathoracic Lymph Nodes in Non-Small Cell Lung Cancer Redundant: A Prospective Study. Thorax, 62, 696-701. http://dx.doi.org/10.1136/thx.2006.072959
[10]	Barnard, J., Dunning, J., Musleh, G. and Odom, N. (2004) Is There a Role for the Use of Radical Lymph Node Dissection in the Surgical Management of Resectable Non-Small Cell Lung Cancer? Interactive Cardiovascular and Thoracic Surgery, 3, 294-299. http://dx.doi.org/10.1016/j.icvts.2003.12.004
[11]	Wu, Y.L., Huang, Z.F., Wang, S.Y., Yang, X.N. and Ou, W. (2002) A Randomized Trial of Systematic Nodal Dissection in Resectable Non-Small Cell Lung Cancer. Lung Cancer, 36, 1-6. http://dx.doi.org/10.1016/S0169-5002(01)00445-7
[12]	Doddoli, C., Aragon, A., Barlesi, F., Chetaille, B., Robitail, S., Giudicelli, R., Fuentes, P. and Thomas, P. (2005) Does the Extent of Lymph Node Dissection Influence Outcome in Patients with Stage I Non-Small-Cell Lung Cancer? European Journal Cardio-Thoracic Surgery, 27, 680-685. http://dx.doi.org/10.1016/j.ejcts.2004.12.035
[13]	Izbicki, J.R., Thetter, O., Habekost, M., Karg, O., Passlick, B., Kubuschok, B., Busch, C., Haeussinger, K., Knoefel, W.T., Pantel, K. and Schweiberer, L. (1994) Radical Systematic Mediastinal Lymphadenectomy in Non-Small Cell Lung Cancer: A Randomized Controlled Trial. British Journal of Surgery, 81, 229-235. http://dx.doi.org/10.1002/bjs.1800810223
[14]	Sugi, K., Nawata, K., Fujita, N., Ueda, K., Tanaka, T., Matsuoka, T., Kaneda, Y. and Esato, K. (1998) Systematic Lymph Node Dissection for Clinically Diagnosed Peripheral Non-Small-Cell Lung Cancer Less than 2 cm in Diameter. World Journal of Surgery, 22, 290-294; Discussion 294-295. http://dx.doi.org/10.1007/s002689900384
[15]	Lardinois, D., Suter, H., Hakki, H., Rousson, V., Betticher, D. and Ris, H.B. (2005) Morbidity, Survival, and Site of Recurrence after Mediastinal Lymph-Node Dissection versus Systematic Sampling after Complete Resection for Non-Small Cell Lung Cancer. The Annals of Thoracic Surgery, 80, 268-274; Discussion 274-275.
[16]	Gajra, A., Newman, N., Gamble, G.P., Kohman, L.J. and Graziano, S.L. (2003) Effect of Number of Lymph Nodes Sampled on Outcome in Patients with Stage I Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 21, 1029-1034. http://dx.doi.org/10.1200/JCO.2003.07.010
[17]	Ludwig, M.S., Goodman, M., Miller, D.L. and Johnstone, P.A. (2005) Postoperative Survival and the Number of Lymph Nodes Sampled during Resection of Node-Negative Non-Small Cell Lung Cancer. Chest, 128, 1545-1550. http://dx.doi.org/10.1378/chest.128.3.1545
[18]	Berardi, R., Onofri, A., Savini, A., Caramanti, M., Chiorrini, S., Santinelli, A., Brunelli, A., Zuccatosta, L., Mazzanti, P., Pierantoni, C., Scartozzi, M., Sabbatini, A., Gasparini, S. and Cascinu, S. (2011) Relationship of Number of Resected Lymph Nodes in Early-Stage Non-Small Cell Lung Cancer (NSCLC) and Survival. Journal of Clinical Oncology, 29.
[19]	Allen, M.S., Darling, G.E., Pechet, T.T., Mitchell, J.D., Herndon II, J.E., Landreneau, R.J., Inculet, R.I., Jones, D.R., Meyers, B.F., Harpole, D.H., Putnam Jr., J.B. and Rusch, V.W. (2006) Morbidity and Mortality of Major Pulmonary Resections in Patients with Early-Stage Lung Cancer: Initial Results of the Randomized, Prospective ACOSOG Z0030 Trial. The Annals of Thoracic Surgery, 81, 1013-1019. http://dx.doi.org/10.1016/j.athoracsur.2005.06.066
[20]	Handy Jr., J.R., Asaph, J.W., Skokan, L., Reed, C.E., Koh, S., Brooks, G., Douville, E.C., Tsen, A.C., Ott, G.Y. and Silvestri, G.A. (2002) What Happens to Patients Undergoing Lung Cancer Surgery? Outcomes and Quality of Life before and after Surgery. Chest, 122, 21-30. http://dx.doi.org/10.1378/chest.122.1.21
[21]	Ilic, N., Petricevic, A., Arar, D., Kotarac, S., Banovic, J., Ilic, N.F., Tripkovic, A. and Grandic, L. (2007) Skip Mediastinal Nodal Metastases in the IIIa/N2 Non-Small Cell Lung Cancer. Journal of Thoracic Oncology, 2, 1018-1021. http://dx.doi.org/10.1097/JTO.0b013e318158d471
[22]	Okada, M., Tsubota, N., Yoshimura, M. and Miyamoto, Y. (1998) Proposal for Reasonable Mediastinal Lymphadenectomy in Bronchogenic Carcinomas: Role of Subcarinal Nodes in Selective Dissection. The Journal of Thoracic and Cardiovascular Surgery, 116, 949-953. http://dx.doi.org/10.1016/S0022-5223(98)70045-5
[23]	Arriagada, R., Auperin, A., Burdett, S., Higgins, J.P., Johnson, D.H., Le Chevalier, T., Le Pechoux, C., Parmar, M.K., Pignon, J.P., Souhami, R.L., Stephens, R.J., Stewart, L.A., Tierney, J.F., Tribodet, H. and van Meerbeeck, J. (2010) Adjuvant Chemotherapy, with or without Postoperative Radiotherapy, in Operable Non-Small-Cell Lung Cancer: Two Meta-Analyses of Individual Patient Data. Lancet, 375, 1267-1277.
[24]	Goldstraw, P., Ball, D., Jett, J.R., Le Chevalier, T., Lim, E., Nicholson, A.G. and Shepherd, F.A. (2011) Non-SmallCell Lung Cancer. Lancet, 378, 1727-1740. http://dx.doi.org/10.1016/S0140-6736(10)62101-0
[25]	Mountain, C.F. (1997) Revisions in the International System for Staging Lung Cancer. Chest, 111, 1710-1717. http://dx.doi.org/10.1378/chest.111.6.1710