Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.
Humans ; Male ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/*diagnosis/pathology/surgery ; Protein Isoforms/blood ; Protein Precursors/*blood ; Sensitivity and Specificity ; Severity of Illness Index ; Tumor Markers, Biological/blood

PURPOSE: Prostate cancer is the most frequent cancer in men in Europe. A major focus in urology is the identification of new biomarkers with improved accuracy in patients with low-risk prostate cancer. Here, we evaluated two-dimensional neovascular complexity in prostate tumor and nontumor biopsy cores by use of a computer-aided image analysis system and assessed the correlations between the results and selected clinical and pathological parameters of prostate carcinoma. MATERIALS AND METHODS: A total of 280 prostate biopsy sections from a homogeneous series of 70 patients with low-risk prostate cancer (Gleason score 3+3, prostate-specific antigen [PSA]<10 ng/mL, and clinical stage T1c) who underwent systematic biopsy sampling and subsequent radical prostatectomy were analyzed. For each biopsy, 2-microm sections were treated with CD34 antibodies and were digitized by using an image analysis system that automatically estimates the surface fractal dimension. RESULTS: Our results showed that biopsy sections without cancer were significantly more vascularized than were tumors. No correlations were found between the vascular surface fractal dimension and patient's age, PSA and free-to-total PSA ratios, pathological stage, Gleason score, tumor volume, vascular invasion, capsular penetration, surgical margins, and biochemical recurrence. CONCLUSIONS: The value of angiogenesis in prostate cancer is still controversial. Our findings suggest that low-risk prostate cancer tissues are less vascularized than are nontumor tissues. Further studies are necessary to understand whether angiogenesis is a hallmark of intermediate- and high-risk prostate cancer.
Adult ; Aged ; Biopsy, Needle ; Fractals ; Humans ; Image Processing, Computer-Assisted/methods ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Neovascularization, Pathologic/*pathology ; Prostate/*blood supply ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Neoplasms/*blood supply/pathology/surgery ; Retrospective Studies