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Division of Thoracic Surgery, Yale University, FMB 128, 330 Cedar St, New Haven, CT 06520-8062
(Email: frank.detterbeck{at}yale.edu).
Misthos and colleagues [1] have performed an interesting retrospective analysis of a fairly large cohort of resected patients who were found to be N2 positive after complete resection. They have confirmed what others have demonstrated: that single station N2 involvement carries a better prognosis than multi-station N2 involvement [2, 3].
This study has several limitations. It is unfortunate that the policy toward preoperative staging is described merely as involving "different means." This is a particular issue because the level of postoperatively discovered N2 disease is one of the highest reported (23%). Moreover, two thirds of these patients had multi-station N2 node involvement, further suggesting that preoperative staging was limited. A change in the policy toward preoperative staging during the course of this study could well confound the results, especially because the analysis did not include an assessment of outcomes by time period during the study.
Despite the suggestion that preoperative staging was limited, the survival of pN2 patients was remarkably good. It must be remembered that incompletely resected patients were excluded from the study, which accounts for 25% to 35% of pN2 patients [3]. The fact that only 3-year survival is reported makes it harder to compare this study with other series. Data on the follow-up is not provided, although some data is available from the Kaplan–Meier curve. It is interesting that the study is described as "immature," although patient enrollment occurred from 1993 to 2004. Nevertheless, the 3-year survival of these R0 resected single and multi-station positive pN2 patients of 43% and 19% in this study is roughly the same as the average reported 5-year survival of 33% and 13% in other series [3].
Most surprising is that this study ignores the careful analysis of the International Association for the Study of Lung Cancer (IASLC) staging committee on nodal factors that was published in the Journal of Thoracic Oncology in 2007 [2]. This analysis involved 5,770 patients (compared with 302 patients in this study). The IASLC analysis also found that multi-station involvement was a poor prognostic factor. They also found, consistent with this study, that none of the N2 stations carried a significantly different prognosis (ie, aortopulmonary window nodes) and did not clearly demonstrate that a skip metastasis (eg, N2 involvement without N1 involvement) was associated with a better outcome.
What is the "take home message" that can be derived from the study by Misthos and colleagues [1]? Certainly there is prognostic data regarding pN2 patients that further corroborates other work. The lack of a difference in outcomes between N2 involvement in regional versus nonregional N2 nodes argues that a lobe-specific node dissection or systematic sampling may not be justified. The high rate of N2 node involvement seems to underscore the importance of preoperative staging, but the relatively good survival weakens this argument. The study does provide justification to proceed with a resection if unsuspected N2 disease is detected intraoperatively. Given the retrospective nature of the study (ie, the lack of data about confounding factors and intermediate follow-up), further inferences are not warranted.
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