The prognostic value of vascular endothelial growth factor in patients with renal cell carcinoma: a systematic review of the literature and meta-analysis

Abstract

Objective: Vascular endothelial growth factor (VEGF) serum level or tumor expression may be prognostic in renal cell carcinoma (RCC). The purpose of this meta-analysis was to examine the prognostic value of serum VEGF level and tumor expression in patients with RCC.Methods: PubMed and EMBASE databases were searched until September 26, 2016. Prospective and retrospective studies of RCC patients that had VEGF levels measured were included. Outcome measures were overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS).Results: A total of 14 studies were included in the meta-analysis. In patients with RCC, elevated serum VEGF level was not associated with OS (pooled hazard ratio [HR] = 1.16; 95% confidence interval [CI]: 0.52 to 2.60; p = 0.716), but was associated with poor DSS (pooled HR = 4.22; 95% CI: 2.02 to 8.79; p < 0.001) and PFS (pooled HR = 1.50; 95% CI: 1.22 to 1.85; p < 0.001). Removal of one study, however, resulted in elevated serum level being associated with poorer OS. Tumor VEGF expression was not associated with OS (pooled HR = 1.48; 95% CI: 0.74 to 2.95; p = 0.263), but was associated with worse DSS (pooled HR = 1.83; 95% CI: 1.24 to 2.71; p = 0.003). Conclusion:In patients with RCC, elevated serum VEGF level is associated with worse OS, DSS, and PFS, while tumor expression is only associated with worse DSS. The number of studies, however, was limited and the results should be interpreted with caution.

Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade

“…Several clinical trials combining ICIs with Bevacizumab are also ongoing in mRCC ( Table 1 ), in which elevated serum and tumor VEGF levels have been associated with poor survival ( 249 ). In a study combining Bevacizumab with Atezolizumab, the authors demonstrated the ability of Bevacizumab to induce a Th1 signature with chemokines involved in lymphocyte trafficking, tumor MHC I protein expression and infiltration of tumor-specific T cell clones.…”

The Prognostic Value of Systemic Inflammatory Markers in Advanced Renal Cell Carcinoma Patients Treated With Molecular Targeted Therapies

“…They showed that the level of VEGF is inversely correlated with the levels of Alb and NLR. In a meta-analysis, Shen et al showed that elevated serum VEGF level is associated with worse OS, disease specific survival (DSS) and PFS in patients with RCC (28).…”

Synergies of Antiangiogenic Therapy and Immune Checkpoint Blockade in Renal Cell Carcinoma: From Theoretical Background to Clinical Reality

“…There is a broad sense that tumor immune evasion closely relates to angiogenesis, and, in turn, tumor angiogenesis highly depends on immunosuppressive microenvironment, which is companion processes in tumorigenesis ( Figure 2 ) ( 40 ). Mounting evidence now show that elevated level of VEGF in tumor lesion may cause suppression in both innate and adaptive immune response, and increased serum or tumor VEGF levels are associated with unfavorable prognosis in mRCC patients ( 41 ). Reportedly, VEGF can inhibit the innate immune system via hampering the transcriptional program required for maturation of DCs, the critical cells in immune activation, and increasing the presence of MDSCs, which represent a heterogeneous population of cells that accumulate in tumor-bearing hosts, characteristic by their potent immune-suppressive activity against cytotoxic tumor-infiltrating lymphocytes (TIL) ( 42 – 45 ).…”