Abstract
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.
Highlights
Prostate cancer is the most commonly diagnosed cancer in men in the Western world, with a median age at diagnosis of 66 years [1]
Later studies have failed to confirm that Microvessel density (MVD) is an independent prognostic factor in untreated tumors, and no correlation has yet been established between MVD and effectiveness of anti-angiogenic treatment in prostate cancer [44]
In prostate cancer a high-level vascular endothelial growth factor (VEGF)-A expression has been found in endothelial cells, and in tumor cells [53]. These findings suggest that angiogenesis is important in prostate cancer, prompting subsequent clinical studies to assess whether anti-angiogenesis therapy is effective in the treatment of prostate cancer
Summary
Prostate cancer is the most commonly diagnosed cancer in men in the Western world, with a median age at diagnosis of 66 years [1]. The current treatment options in prostate cancer will be discussed, along with a summary of what is already known in relation to angiogenesis in cancer. This will be followed by the literature review on angiogenesis and anti-angiogenic therapies in prostate cancer, . The five-year relative survival rate for men diagnosed in the USA between 2001 and 2007 with local or regional disease was 100%, whilst the rate for distant disease was 28.7% [5]. UK statistics show similar results: the five-year relative survival for prostate cancer was 100% in localized disease and 30% in distant disease for patients diagnosed during 2002–2006 in the former Anglia Cancer Network [6]. Prostate cancer can present with decreased urinary stream, urgency, hesitancy, nocturia, or incomplete bladder emptying, but these symptoms are non-specific and are infrequent at diagnosis [7]
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