Introduction: High circulating serum vascular endothelial growth factor (VEGF) levels might reflect enhanced angiogenesis in patients suffering from non-small cell lung cancer (NSCLC). This study aimed at determining the prognostic significance of circulating VEGF as a prognostic factor in NSCLC.
Methods: Four hundred fifty-one histologically or cytologically proven and previously untreated NSCLC patients have been studied. Median follow-up was 13 years and 9 months. Eleven clinical and biologic variables were recorded. The levels of circulating VEGF were measured in the serum by quantitative immunoassay. Patients have had received conventional treatment (without anti-VEGF therapy) according to the international guidelines. All statistical tests were two-sided.
Results: Receiver operating characteristic curves (area under the ROC curve: 0.66 +/- 0.05) showed that circulating VEGF serum level did not demonstrate a high sensitivity-specificity relationship, and therefore, demonstrated a low ability to differentiate NSCLC from benign lung diseases. A 600 pg/mL level of circulating VEGF serum was considered as threshold with 40.8% of NSCLC patients presenting with a high level. The circulating VEGF distribution differed significantly according to disease stage, nodal status, and performance status (PS), with the highest levels observed in metastatic stage, positive mediastinal nodal status, and poor PS. In univariate survival analysis, patients with a high pretreatment circulating VEGF serum level proved to have a shorter overall survival when compared with patients presenting with a circulating VEGF serum level </=600 pg/mL. However, in the Cox proportional hazard model, this variable was not included in the panel of independent determinants of a poor outcome that was as follows: advanced or metastatic diseases according to the 6th edition of the staging system, PS >/=2, nodal status N2-3, metastatic disease, neuron-specific enolase >12.5 ng/mL, CYFRA 21-1 >3.6 ng/mL.
Conclusion: The prognostic information given by a high circulating VEGF serum level is not an independent determinant of survival owing to a high relationship with main prognostic variables such as PS, stage of the disease, and nodal status. This finding does not preclude a putative prognostic impact of in situ detection of VEGF and VEGF receptors in tumor specimen.