Prostate cancer is the most commonly diagnosed
cancer among men in the Western world. Although localized disease can be effectively treated with established surgical and
radiopharmaceutical treatments options, the prognosis of
castration-resistant advanced
prostate cancer is still disappointing. The objective of this study was to review the role of angiogenesis in
prostate cancer and to investigate the effectiveness of anti-angiogenic
therapies. A literature search of clinical trials testing the efficacy of anti-angiogenic
therapy in
prostate cancer was performed using Pubmed.
Surrogate markers of angiogenic activity (microvessel density and
vascular endothelial growth factor A (
VEGF-A) expression) were found to be associated with
tumor grade,
metastasis, and prognosis. Six randomizedstudies were included in this review: two phase II trials on localized and
hormone-sensitive disease (n = 60 and 99 patients) and four phase III trials on
castration-resistant refractory disease (n = 873 to 1224 patients). Although the phase II trials showed improved relapse-free survival and stabilisation of the disease, the phase III trials found increased toxicity and no significant improvement in overall survival. Although angiogenesis appears to have an important role in
prostate cancer, the results of anti-angiogenic
therapy in
castration-resistant refractory disease have hitherto been disappointing. There are various possible explanations for this lack of efficacy in
castration-resistant refractory disease: redundancy of angiogenic pathways, molecular heterogeneity of the disease, loss of
tumor suppressor protein phosphatase and
tensin homolog (PTEN) expression as well as various
VEGF-A splicing
isoforms with pro- and anti-angiogenic activity. A better understanding of the molecular mechanisms of angiogenesis may help to develop effective anti-angiogenic
therapy in
prostate cancer.