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Prognostic relevance of angiogenesis in stage III NSCLC receiving multimodality treatment

¹ Dept of Thoracic Oncology, Thoraxklinik, University of Heidelberg, ³ Dept of Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, ² Dept of Medicine, Haematology/Oncology, University of Münster, ⁵ Dept of Medical Informatics and Biomathematics, University of Münster, Münster, ⁴ Institute of Pathology, Klinikum Bremen-Mitte, Bremen, Germany. ⁶ Both contributed equally as senior authors.

CORRESPONDENCE: M. Kreuter, Dept of Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Amalienstr. 5, 69126 Heidelberg, Germany. Fax: 49 62213961202. E-mail: michael.kreuter{at}thoraxklinik-heidelberg.de

Keywords: Angiogenesis, lymph node metastases, microvessel density, multimodality treatment, nonsmall cell lung cancer

Received: August 6, 2008
Accepted January 20, 2009

Compelling evidence indicates that microvessel density (MVD) is a prognostic marker in early nonsmall cell lung cancer (NSCLC). However, its role in lymph node metastases in stage III NSCLC receiving multimodality treatment is unknown.

Lymph nodes of 142 patients with stage III NSCLC, treated in a trial of the German Lung Cancer Cooperative group, were evaluated for MVD. Median follow-up was 7.39 yrs. MVD was correlated with demographic and tumour-related variables and survival.

MVD (median 33.9) did not correlate with survival. However, in multimodality-treated stage IIIA patients receiving tumour resection with negative margins (R0), those with a high MVD had significantly prolonged overall survival with a median of 4.96 yrs compared with 1.99 yrs for those with low MVD (p = 0.041). Cox regression analysis revealed that MVD was a prognostic factor in R0-resected stage IIIA (hazard ratio 0.417). Furthermore, a significant correlation of MVD to stage was observed, with significantly lower MVD in stage IIIA than IIIB (p = 0.0062), and a significant correlation of MVD to histological subtype was observed, with adenocarcinoma revealing the highest scores (p = 0.0001).

Increased angiogenesis within lymph node metastases is a prognostic indicator for better survival in NSCLC patients. Thus, measurement of MVD might be useful in selecting patients for future neoadjuvant treatment decisions.