Abarelix and other gonadotrophin-releasing hormone antagonists in prostate cancer.

Hormonal therapy is the main recommended treatment for locally advanced and metastatic prostate cancer. Luteinizing hormone-releasing hormone (LHRH) agonists, such as buserelin, goserelin, leuprorelin and triptorelin, stimulate the pituitary's gonadotrophin-releasing hormone (GnRH) receptor, ultimately leading to its de-sensitization and subsequent reduction of LH and testosterone levels. However, this reduction is accompanied by a well described increase or 'surge' in LH and testosterone levels, necessitating the concomitant administration of an antiandrogen to combat the potential effects of transient acceleration in cancer activity. Two pure GnRH antagonists have been developed, abarelix and degarelix, that are devoid of any agonist effect on the GnRH receptor and consequently do not result in testosterone flare. Abarelix was the first GnRH antagonist to be developed and was approved by the USA Food and Drug Administration in 2004 for the initiation of hormonal castration in advanced or metastasizing hormone-dependent prostate carcinoma, when rapid androgen suppression is necessary. Clinical data on both abarelix and degarelix show that they can produce rapid and sustained decreases in testosterone to castrate levels without the need for co-administration of an antiandrogen, and with a very low complication rate in the short term.

Prostate cancer diagnosis in the new millennium: strengths and weaknesses of prostate-specific antigen and the discovery and clinical evaluation of prostate cancer gene 3 (PCA3).

The decision to take a prostate biopsy is traditionally guided by a digital rectal examination and measurement of serum total prostate-specific antigen (tPSA). However, both techniques are subject to inherent weaknesses. The prostate cancer gene 3 (PCA3), a gene-based marker, specific for prostate cancer, supplements the predictive power of tPSA to improve diagnosis of disease. Including this new marker in the standard of care for men at risk of prostate cancer should be considered, as it presents marked potential for better decision making for a prostate biopsy and for improving overall patient care.

The current status of robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is a rapidly evolving technique for the treatment of localized prostate cancer. In the United States, over 65% of radical prostatectomies are robot-assisted, although the acceptance of this technology in Europe and the rest of the world has been somewhat slower. This article reviews the current literature on RARP with regard to oncological, continence and potency outcomes-the so-called 'trifecta'. Preliminary data appear to show an advantage of RARP over open prostatectomy, with reduced blood loss, decreased pain, early mobilization, shorter hospital stay and lower margin rates. Most studies show good postoperative continence and potency with RARP; however, this needs to be viewed in the context of the paucity of randomized data available in the literature. There is no definitive evidence to show an advantage over standard laparoscopy, but the fact that this technique has reached parity with laparoscopy within 5 years is encouraging. Finally, evolving techniques of single-port robotic prostatectomy, laser-guided robotics, catheter-free prostatectomy and image-guided robotics are discussed.

Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer: the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors.

A cure cannot be assured for all men with clinically localized prostate cancer undergoing radical treatment. Molecular markers would be invaluable if they could improve the prediction of occult metastatic disease. This study was carried out to investigate the expression of BCL-2, Ki-67, p53 and E-cadherin in radical prostatectomy specimens. We sought to assess their ability to predict early biochemical relapse in a specific therapeutic setting. Eighty-two patients comprising 41 case pairs were matched for pathological stage, Gleason grade and preoperative prostate-specific antigen (PSA) concentration. One patient in each pair had biochemical recurrence (defined as PSA >or= 0.2 ng mL(-1) within 2 years of surgery) and the other remained biochemically free of disease (defined as undetectable PSA at least 3 years after surgery). Immunohistochemical analysis was performed to assess marker expression on four replicate tissue microarrays constructed with benign and malignant tissue from each radical prostatectomy specimen. Ki-67, p53 and BCL-2, but not E-cadherin, were significantly upregulated in prostate adenocarcinoma compared with benign prostate tissue (P < 0.01). However, no significant differences in expression of any of the markers were observed when comparing patients who developed early biochemical relapse with patients who had no biochemical recurrence. This study showed that expression of p53, BCL-2 and Ki-67 was upregulated in clinically localized prostate cancer compared with benign prostate tissue, with no alteration in E-cadherin expression. Biomarker upregulation had no prognostic value for biochemical recurrence after radical prostatectomy, even after considering pathological stage, whole tumour Gleason grade and preoperative serum PSA level.

Outcomes of robotic assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is a rapidly evolving technique for the treatment of localized prostate cancer. However, cynics point to the increasing role of market forces in the robotic revolution. As yet, Europe has not taken up RARP in large numbers and this may in part relate to the high level of expertise in laparoscopy previously gained. Furthermore, setting up a robotic program is a major undertaking for many surgical units. This article reviews the current literature on RARP with regard to oncologic, continence and potency outcomes - the so called 'trifecta'. Preliminary data appears to show an advantage of RARP over open prostatectomy with reduced blood loss, decreased pain, early mobilization, shorter hospital stay and lower margin rates. Most intra-institutional studies demonstrate good postoperative continence and potency with RARP; however this needs to be viewed in the context of a paucity of randomized data available in the literature. There is no definitive data to show an advantage over standard laparoscopy, but the fact that this technique has reached parity with laparoscopy within 5 years is encouraging.

Allelic imbalance at 13q14.2 approximately q14.3 in localized prostate cancer is associated with early biochemical relapse.

Allelic imbalance (AI), particularly at chromosomes 8p, 10q, and 13q, is the most frequently observed genetic change in sporadic prostate cancer. AI at these sites may inactivate tumor suppressor genes that regulate normal cell growth. To establish the relationship between AI and progression, we analyzed loci on 8p, 10q, and 13q14 in archival prostate tumors matched for Gleason grade, pre-operative prostate-specific antigen levels, and pathologic stage, and they were paired on the basis of relapse status after 3 years. AI was identified in 66% of patients without relapse and in 73% with relapse. There was no statistically significant difference for AI at 8p21.3 and 10q23.2 between the two groups of patients, but significant differences between relapsers and nonrelapsers in the frequency of AI at D13S165 at 13q14.2 (P=0.006) and D13S273 at 13q14.3 (P=0.03). There was also a significantly higher incidence of AI at both loci in the relapsers compared to the nonrelapsers (P=0.03). In three relapsers, AI occurred at all three loci between 13q14.2 and 13q14.3, with no nonrelapsers demonstrating AI at all three loci. These findings show that AI at 13q14.2 approximately q14.3 is an important event in the progression of localized prostate cancer, and suggest a possible role for microRNAs.

Benign prostatic hyperplasia: solutions to an ageing problem.

As the population ages, the demand for treatment of the symptoms of benign prostatic hyperplasia has never been higher. Equally the choice of treatments has never been greater. This review considers the medical and surgical options.

[Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging.male (MSAM-7)]. / Troubles urinaires du bas appareil et dysfonction sexuelle masculine: l'enquête MSAM-7 ou enquête multinationale de l'homme agé.

OBJECTIVES: Lower urinary tract symptoms (LUTS), which are often caused by benign prostatic hypertrophy (BPH), and sexual dysfunction are common in older men, with an overall prevalence of > 50% in men aged > 50 years. Men with LUTS have been reported to experience sexual dysfunction, including ejaculatory loss, painful ejaculation, and erectile dysfunction. This study was conducted to investigate the relationship between LUTS and sexual problems in aging men. METHODS: A large-scale, multinational survey was conducted in the US and six European countries to systematically investigate the relationship between LUTS and sexual dysfunction in older men. Detailed questionnaires were mailed to a national representative sample of men aged 50 to 80 years in each country. Selection was made on the basis of age, occupation, geographie region, and population density. LUTS and sexual function were assessed by validated symptom scales, including the International Prostate Symptom Score, the Danish Prostatic Symptom Score, and the International Index of Erectile Function. Subjects also completed a health and demographics questionnaire. RESULTS: A total of 34,800 surveys were mailed out, 14,254 were completed and returned, and 12,815 were deemed evaluable and included in the analysis. Results were consistent from one country to another. Although 90% of the men had LUTS, only 19% had sought medical help for urinary problems and only 11% were medically treated. Sexual activity was reported by 83% of the sample, with 71% reporting at least one episode of sexual activity during the previous 4 weeks. Sexual disorders and their bothersomeness were strongly related to both age and severity of LUTS. The relationship between sexual problems and LUTS is independent of comorbidities such as diabetes, hypertension, cardiac disease, and hypercholesterolemeia. CONCLUSIONS: Sexual activity is common in a majority of men over age 50 and is an important component of overall quality of life. The presence and severity of LUTS are independent risk factors for sexual dysfunction in older men. These results highlight the clinical importance of evaluating LUTS in patients with sexual dysfunction, and the need to consider sexual issues in the management of patients with benign prostatic hypertrophy.

Measurement of blood E2F3 mRNA in prostate cancer by quantitative RT-PCR: a preliminary study.

The use of serum prostate-specific antigen (PSA) measurements necessitates biopsies for accurate prostate cancer (CaP) diagnosis. Overall efficiency of accurate diagnosis, when PSA levels are used alone, is less than 60%. E2F3 was evaluated as an alternative biomarker using patient blood samples. Expression levels were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and correlated with accurate clinicopathological data. Statistical analysis demonstrated significant differences in E2F3 expression levels (p<0.0001), and high levels of discrimination (receiver operator curve/area under curve analysis values (AUC) >0.88), in particular at early stages of disease development, between benign disease and localized CaP. Limited levels of discrimination were observed at the later stages of disease development, between localized and metastatic disease (p=0.076, AUC=0.633). A cut-off point of 0.34 with high specificity for benign disease (92.3%) and sensitivity for CaP diagnosis (81.0%) was identified. At this cut-off point, 85% patients were correctly diagnosed with either malignant or benign disease. This study demonstrates the strength of E2F3 as a potential marker for discriminating benign and malignant disease, addressing the current limitations of serum PSA measurements.

Diabetes and the urologist: a growing problem.

The incidence of diabetes continues to increase dramatically; this incidence is predominantly of the type-2 form which clusters together with other comorbidities of hypertension and lipid abnormalities, to form the metabolic syndrome. These conditions will have an increasing impact on urological practice, with erectile dysfunction, hypogonadism, voiding difficulties and urinary tract infections all more common in these patients. These symptoms might be the initial presentation of previously undiagnosed diabetes and it is important to recognise this condition early to avoid later complications including end-stage renal failure.