Risk factor stratification can be used to significantly predict the outcome in patients on active surveillance. Prostate specific antigen density 0.08 ng/ml/cc at first rebiopsy was validated as a significant predictor of subsequent progression.

Prostate cancer grading by extended needle biopsy is a better predictor of the final Gleason score than nonextended needle biopsy, as determined by radical prostatectomy histological evaluation. Therefore, extended prostate needle biopsy provides better guidance to determine the appropriate treatment in patients with prostate cancer.

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Androgen receptor (AR) is a ligand-inducible transcription factor, and a member of the steroid-thyroid-retinoid receptor superfamily, that mediates the biological effects of androgens in a wide range of physiological and pathological processes. AR expression was identified in vascular cells nearly 20 years ago, and recent research has shown that AR mediates a variety of actions of androgens in endothelial and vascular smooth muscle cells. In this mini-review, we review evidence indicating the importance of AR in human endothelial cell (HUVEC) homeostatic and pathogenic processes. Although a role for AR in the modulation of HUVEC biology is evident, the molecular mechanisms by which AR regulates HUVEC homeostasis and disease processes are not fully understood. Understanding these mechanisms could provide critical insights into the processes of pathogenesis of diseases ranging from cardiovascular disease to cancer that are major causes of human morbidity and mortality.

Carcinoma-associated fibroblasts (CAF) promote tumor progression of pre-neoplastic epithelial cells. To investigate the basis of this phenomenon, we compared the properties of fibroblasts cultured from normal human prostate (NHPF) to prostate CAF. NHPF and CAF were assayed for growth potential, cell death and proliferative capacity by measuring population doubling time, cell cycle distribution and capability to form colonies in soft agar. Resistance to genotoxic (UV radiation: 0 -50 J/cm 2 ) and chemotoxic (0 -200 nM Taxol) agents were compared between CAF and NHPF by measuring cell viability and cell cycle analysis. Transforming growth factor ␤1 (TGF-␤1) immunoreactivity was assessed in nonmalignant and malignant prostatic tissue. No detectable differences were found when comparing CAF and NHPF with respect to population doubling time, cell cycle distribution and response to genotoxic and chemotoxic agents. The mean number of colonies in soft agar was 120.5 for CAF vs. 18.2 for NHPF (p < 0.05). Because TGF-␤1 and matrix metalloproteinase (MMP)-9 have been associated with growth of fibroblasts in soft agar and tumor promotion, we measured the expression of these factors in NHPF and CAF by ELISA. There was no difference in expression of MMP-9; however, TGF-␤1 was expressed in higher concentrations in CAF than in NHPF (p < 0.0014). Furthermore, TGF-␤1 expression was higher in the carcinoma-associated stroma of prostate cancer tissue than stroma of non-malignant prostatic tissue. Increased capability of CAF as compared to NHPF to form colonies in soft agar may be due to a higher expression of TGF-␤1 and correlates with the ability of CAF to promote malignant progression of prostate epithelial cells. © 2004 Wiley-Liss, Inc. Key words: normal human prostatic fibroblasts; carcinoma-associated fibroblasts; prostate cancer; transforming growth factor-␤; Taxol; UV radiation; soft agarWe have shown previously in an in vivo and in vitro model that an immortalized but nontumorigenic human prostatic epithelial cell line (BPH-1) can be induced to form adenocarcinomas when combined with carcinoma-associated fibroblasts (CAF). 1 In contrast, this effect was not detected when BPH-1 cells were grown with normal human prostatic fibroblasts (NHPF) under the same experimental conditions. Therefore, the stromal compartment can play an important role in tumor growth and progression. This interaction between stromal and epithelial compartments has also been described in normal development of skin, 2 mammary gland, 3 prostate 4 and in other tissues. One of the first studies addressing the stromal-epithelial interaction and its role in tumor growth was reported by Camps et al. 5 They demonstrated that transformed fibroblasts induced human epithelial cells from different organs (prostate, breast and bladder) to form adenocarcinomas in athymic mice.The fibroblast activated microenvironment, as a consequence of stromal-epithelial interaction in tumor progression, modifies not only the behavior of the tumorigenic cells, but also other stroma...

This report presents our experience with T therapy in a cohort of T-deficient men on active surveillance (AS) for Gleason 3 + 3 and Gleason 3 + 4 prostate cancer (PCa). A retrospective chart review identified 28 men with T deficiency who underwent T therapy (T group) for at least 6 months while on AS for PCa. A comparison group of 96 men on AS for PCa with untreated T deficiency (no-T group) was identified at the same institution. The AS protocol followed a modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 + 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T group, 3 (10.7%) men developed an increase in Gleason score while on AS. Of 22 men in the T group with Gleason 3 + 3 disease, 7 (31.8%) men developed biopsy progression including 3 men (13.6%) who developed Gleason 3 + 4 PCa. Of 6 men with Gleason 3 + 4 disease at baseline, 2 (33.3%) men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 + 4. All 96 men in the no-T group had Gleason 3 + 3 disease at baseline and, 43 (44.7%) developed biopsy progression, including 9 men (9.38%) with upgrading to Gleason 7 (3 + 4). Biopsy progression rates were similar for both groups and historical controls. Biopsy progression in men on AS appears unaffected by T therapy over 3 years. Prospective placebo-controlled trials of T therapy in T-deficient men on AS should be considered given the symptomatic benefits experienced by treated men.

ObjectiveTo determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS). Patients and MethodsTotal testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver-operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan-Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. ResultsA total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several-fold increase in the risk of disease reclassification (OR 4.3,). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification. ConclusionsFree testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.

Low age adjusted free T as well as single cutoff free T correlates with poorly differentiated prostate cancer in surgically treated patients.