Can tumor size be a guide for limited surgical intervention in patients with peripheral non-small cell lung cancer? Assessment from the point of viewof nodal micrometastasis

Objective: We sought to determine the critical diameter of a peripheral non -small cell lung cancer tumor less than which no evidence of nodal micromet astasis is present. Methods: Samples of 3081 lymph nodes from 181 patients with stage I periphe ral lung cancer (155 with adenocarcinoma and 26 with squamous cell carcinom a) who had undergone complete resection with systematic lymphadenectomy wer e used in the study. In the samples immunohistochemical staining for cytoke ratin was performed. The expression of vascular endothelial growth factor ( VEGF) at primary sites was also immunohistochemically assessed. Results: Nodal micrometastasis was detected in 44 patients. The mean tumor sizes were 2.2 +/- 1.3 cm (range, 1.0-7.0 cm) in nodal micrometastasis-posi tive adenocarcinoma, 2.1 +/- 0.9 cm (range, 0.5-6.0 cm) in nodal micrometas tasis-negative adenocarcinoma, 4.8 +/- 2.3 cm (range, 2.2-10.0 cm) in nodal micrometastasis-positive squamous cell carcinoma, and 3.2 +/- 2.1 cm (rang e, 0-9.0 cm) in nodal micrometastasis-negative squamous cell carcinoma. The tumor size in the nodal micrometastasis-positive group tended to be greate r than that in the nodal micrometastasis-negative group in squamous cell ca rcinomas, but there was no significant difference in adenocarcinomas. Nodal micrometastasis was not found in patients with squamous cell carcinoma of 2.0 cm or less in diameter. However, nodal micrometastasis was found in 20% (19/95) of the patients with adenocarcinoma of 1.1 to 2.0 cm in diameter a nd even in 4 of 11 patients with adenocarcinoma of 1.0 cm or less. Among th e patients with nodal micrometastasis, survival of patients with vascular e ndothelial growth factor overexpression was worse than that of patients wit hout it. The survival of patients with nodal micrometastasis without vascul ar endothelial growth factor overexpression was comparable with that of pat ients without nodal micrometastasis. Conclusion: A limited surgical intervention without lymphadenectomy is vali dated for squamous cell carcinoma of 2.0 cm or less without pleural involve ment. In adenocarcinoma the tumor size itself is not a reliable guide for n odal micrometastasis status. In patients with nodal micrometastasis with va scular endothelial growth factor overexpression, the risk of systemic disea se should be considered.