When and Why to Perform Nodal Dissection in Early-Stage Non-Small Cell Lung Cancer?

We have read with interest the article by Zhang et al[1] focused on identification of prognostic factors between T1aN0M0 and T1bN0M0 patients.

In 2009, the seventh edition of TNM Classification of Malignant Tumors [2] has divided T1 patients in two subgroups introducing a 2-cm cut point in consideration of several studies, demonstrating that prognosis is statistically better in patients with tumor from 0 to 2 cm than from 2 to 3 cm. Authors' results are in agreement with this evidence since reported a 5-year survival rate, respectively, of 73.98 and 68.18% in T1a and T1b patients (p = 0.0135).

At the same time, they analyzed prognostic factors for each stage I subgroups and surprisingly found that removal of six or more lymph node stations and removal of lymph node station 7 were independent favorable prognostic factors in T1bN0M0 but not in T1aN0M0. This result complies only in part with the tendency to perform extensive lymphadenectomy even in N0 cases.[3] [4] In fact, the authors demonstrated that when tumor size is less than 2 cm, the number of lymph node stations removed is not associated with any survival improvement.

Their conclusion is that nodal dissection should be proposed in T1bN0M0 patients with therapeutic intent, whereas nodal sampling should be performed in T1aN0M0 to confirm preoperative stage.

Some considerations need to be done. They are as follows:

• First, the explanation of nodal removal utility in stage I disease is uncertain. One hypothesis is that having more nodes dissected increases the staging accuracy, upstaging patients who would have otherwise been included in N0 group. This hypothesis denies therapeutic role of lymph nodes removal.

• Second, the authors report that overall survival was obtained considering only patients died of recurrent disease. However, they did not report the time interval between surgery and relapses. Moreover, they did not report where relapses presented (lymph nodes, ipsilateral parenchyma, and contralateral parenchyma). We think that it should be very interesting to investigate any relationship between extension of lymphadenectomy and different patterns of recurrences presentation. This information could be useful to understand the effective role of nodes removal and its explanation.

• Third, we underline that when nodal sampling is recommended, as in T1aN0M0 patients, at least six nodes should be always removed according to the seventh TNM edition about minimum number of lymph nodes needed for histological examination.[2]

• Finally, we underline the role of positron emission tomography/computed tomography scan in preoperative staging to predict prognosis and determine surgical strategy, also for nodal management, based on tumor metabolic activity. Tsutani et al in a recent article identified tumor size less than 0.8 cm or SUVmax less than 1.5 as predictive criteria of pN0, helpful for avoiding systematic lymphadenectomy for clinical stage IA lung adenocarcinoma, even in T1b tumors.[5]

In conclusion, we appreciate authors' article because it focuses the attention on a less invasive surgical approach in case of early-stage non-small cell lung cancer.

• References

• 1 Zhang Z, Wang A, Zhan Z, Sun L, Chen K, Wang C. T1aN0M0 and T1bN0M0 Non-Small Cell Lung Cancer: A Retrospective Study of the Prognosis. Thorac Cardiovasc Surg 2012; (e-pub ahead of print). DOI: 10.1055/s-0032-1329191.
• 2 Goldstraw P, Crowley J , et al; International Association for the Study of Lung Cancer International Staging Committee; Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007; 2 (8) 706-714
• 3 Ou SH, Zell JA. Prognostic significance of the number of lymph nodes removed at lobectomy in stage IA non-small cell lung cancer. J Thorac Oncol 2008; 3 (8) 880-886
• 4 Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003; 21 (6) 1029-1034
• 5 Tsutani Y, Miyata Y, Nakayama H , et al. Prediction of pathologic node-negative clinical stage IA lung adenocarcinoma for optimal candidates undergoing sublobar resection. J Thorac Cardiovasc Surg 2012; 144 (6) 1365-1371
• 1 Naruke T. Significance of lymph node metastases in lung cancer. Semin Thorac Cardiovasc Surg 1993; 5 (3) 210-218
• 2 Izbicki JR, Passlick B, Pantel K , et al. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer: results of a prospective randomized trial. Ann Surg 1998; 227 (1) 138-144
• 3 Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003; 21 (6) 1029-1034
• 4 Wu YC, Lin C-FJ, Hsu WH, Huang BS, Huang MH, Wang LS. Long-term results of pathological stage I non-small cell lung cancer: validation of using the number of totally removed lymph nodes as a staging control. Eur J Cardiothorac Surg 2003; 24 (6) 994-1001
• 5 Izbicki JR, Passlick B, Hosch SB , et al. Mode of spread in the early phase of lymphatic metastasis in non-small-cell lung cancer: significance of nodal micrometastasis. J Thorac Cardiovasc Surg 1996; 112 (3) 623-630
• 6 Gu CD, Osaki T, Oyama T , et al. Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected nonsmall cell lung cancer: impact on recurrence and Survival. Ann Surg 2002; 235 (1) 133-139
• 7 Ou SH, Zell JA. Prognostic significance of the number of lymph nodes removed at lobectomy in stage IA non-small cell lung cancer. J Thorac Oncol 2008; 3 (8) 880-886
• 8 De Zoysa MK, Hamed D, Routledge T, Scarci M. Is limited pulmonary resection equivalent to lobectomy for surgical management of stage I non-small-cell lung cancer?. Interact Cardiovasc Thorac Surg 2012; 14 (6) 816-820
• 9 Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003; 21 (6) 1029-1034
• 10 Doddoli C, Aragon A, Barlesi F , et al. Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?. Eur J Cardiothorac Surg 2005; 27 (4) 680-685
• 11 Goldstraw P, Crowley J, Chansky K , et al. International Association for the Study of Lung Cancer International Staging Committee; Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007; 2 (8) 706-714