The Prognostic Significance of Isolated Tumor Cells and Micrometastases in Patients with Non-Small Cell Carcinoma of the Lung: A Prospective Study of 233 Patients with Immunohistochemistry and Survival Analysis
R Gupta, RJ Mckenna Jr, D Kusuanco, J Mirocha, AM Marchevsky. Cedars Sinai Medical Center, LA, CA
Background: Current AJCC staging guidelines stratify lymph node metastases into isolated tumor cells (ITC), micrometastases (MM) and metastases. It remains uncertain whether the nodal status of NSCLC patients should be upstaged in the presence of ITC or MM.
Design: 233 NSCLC patients with pN0 at mediastinoscopy underwent VATS lobectomy along with mediastinal lymph node dissection. The presence of ITC and MM was evaluated in 2197 lymph nodes using keratin AE1/AE3 antibody. Selected lymph nodes were also immunostained for calretinin to exclude the possibility of mesothelial inclusions. Nodal status were classified as pN0, pN0 (i+), pN1 (mi), pN1, pN2 (mi), or pN2. Overall survival data were analyzed with Kaplan-Meier statistics by nodal status. Survival for patients with pN0, pN0 (i+), pN1(mi), pN2(i+) and pN2(mi) and pN1 with pN2(i+) and pN2(mi) were compared. Power analysis was performed to determine the sample size required to exclude the possibility of a type II statistical error.
Results: Median follow-up was 56 months. Lymph nodes resected by mediastinal dissection after lobectomy showed nodal metastases in lymph nodes that were not sampled during initial mediastinoscopy in 48 pN1 and 28 pN2 patients. ITC and MM were detected in 63 lymph nodes from 51 patients (21.9%). This finding would have upstaged 4, 24 and 23 patients to pN0 (i+), pN1 (mi) and pN2 (mi) respectively. As expected, there were significant survival differences for patients with pN0, pN1 and pN2 disease. Survival analysis estimated a hazard ratio of 0.76. Change of nodal status resulting from the detection of ITC or MM was not associated with significant survival differences. Power analysis estimated that 304 patients with MM and ITC followed for 60 months would be required to obtain 80% power.
Conclusions: Lymph nodes obtained by lobectomy or mediastinal resection changed the nodal status to either pN1 or pN2 of 32.6 % of patients that were diagnosed as pN0 at concurrent mediastinoscopy. ITC and MM were detected in 21.9% of patients studied with IHC but were not significant prognostic features for NSCLC patients. The results underscore the need to perform power analysis in studies that evaluate the association between ITC-MM and survival.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 230, Monday Morning