Microvessel density as a prognostic factor in non-small-cell lung carcinoma: a meta-analysis of individual patient data.

BACKGROUND: Angiogenesis is a potential prognostic factor that has been investigated in patients with non-small-cell lung carcinoma. However, published studies of the role of angiogenesis as a prognostic factor are inconclusive. We aimed to collect individual patient data to assess microvessel-density counts (ie, a measure of angiogenesis) as a prognostic factor in non-small-cell lung carcinoma. METHODS: We obtained published and unpublished datasets and extracted appropriate data, taking particular care to ensure data quality. Detailed information was obtained for the laboratory methods used by every research centre that generated the data. The outcome of interest was overall survival. We did a meta-analysis to estimate the prognostic role of microvessel density by combining separately estimated hazard ratios (HR) from every study, which were adjusted for tumour stage and age. Analyses were done separately for studies that used the Chalkley method or for those that counted all microvessels. FINDINGS: 17 centres provided data for 3200 patients, 2719 of which were included in the analysis. All but three centres (datasets 9, 10, and 13-367 cases) had already published their findings, and six had updated follow-up information (datasets 1, 2, 3, 6, 7, and 8-1273 cases). For all but three centres (datasets 4, 11, and 13) some data corrections were necessary. For microvessel density counts obtained by the Chalkley method, the HR for death per extra microvessel was 1.05 (95% CI 1.01-1.09, p=0.03) when analysed as a continuous variable. For microvessel density counts obtained by the all vessels method, the HR for death per ten extra microvessels was 1.03 (0.97-1.09, p=0.3) when analysed as a continuous variable. INTERPRETATION: Microvessel density does not seem to be a prognostic factor in patients with non-metastatic surgically treated non-small-cell lung carcinoma. This conclusion contradicts the results of a meta-analysis of published data only. Therefore, the methodology used to assess prognostic factors should be assessed carefully.