Richard Berges

The Evolving Role of Oestrogens and Their Receptors in the Development and Progression of Prostate Cancer

CONTEXT Oestrogens were proven effective in the hormonal treatment of advanced prostate cancer (PCa) >60 yr ago and are still used as second-line hormonal therapy. Paradoxically, oestrogens might also be involved in the development and progression of PCa. OBJECTIVE To examine mechanisms of how oestrogens may affect prostate carcinogenesis and tumour progression. EVIDENCE ACQUISITION Recent data obtained from animal, experimental, and clinical studies were reviewed. EVIDENCE SYNTHESIS The human prostate is equipped with a dual system of oestrogen receptors (oestrogen receptor alpha [ERalpha], oestrogen receptor beta [ERbeta]) that undergoes profound remodelling during PCa development and tumour progression. In high-grade prostatic intraepithelial neoplasia (HGPIN), the ERalpha is upregulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. Preliminary clinical studies with the ERalpha antagonist toremifene have identified the ERalpha as a promising target for PCa prevention. The partial loss of the ERbeta in HGPIN indicates that the ERbeta acts as a tumour suppressor. The ERbeta is generally retained in hormone-naïve PCa but is partially lost in castration-resistant disease. The progressive emergence of the ERalpha and the oestrogen-regulated progesterone receptor (PR) during PCa progression and hormone-refractory disease suggests that these tumours can use oestrogens and progestins for their growth. The TMPRSS2-ERG gene fusion recently reported as a potentially aggressive molecular subtype of PCa is regulated by ER-dependent signalling. TMPRSS2-ERG expression has been found to be increased by ERalpha agonist (oestrogens) and decreased by ERbeta agonists. CONCLUSIONS Oestrogens and their receptors are implicated in PCa development and tumour progression. There is significant potential for the use of ERalpha antagonists and ERbeta agonists to prevent PCa and delay disease progression. Tumours equipped with the pertinent receptors are potential candidates for this new therapeutic approach.

Male lower urinary tract symptoms and related health care seeking in Germany

Objectives: To investigate the prevalence of lower urinary tract symptoms (LUTS) and LUTS– related health care issues in the male population between the ages of 50 and 80 in Germany. Methods: 8,973 randomly chosen men in the age group of interest received by mail a self–administered questionnaire addressing voiding symptoms and bother, common health status, and social demographic as well as health care resources related issues. Results: Of 6,031 (67.2%) returned questionnaires, 5,404 (60.2%) were properly filled out and entered into the database. Of these, 5,004 (56%) completed all IPSS questions. 3,539 (70.7%) of the men presented with no or mild LUTS (IPSS 0–7), 1,465 (29,3%) with moderate to severe voiding symptoms (IPSS >7), respectively. From logistic regression analysis it appears that mainly bother from voiding symptoms as well as incomplete emptying and week stream induced a visit to the doctor. Of men with moderate symptoms (IPSS 8–19), 40% did not report any bother. Conclusion: LUTS is a common condition among German elderly males. In general, bother from LUTS seem to have more effects on health care seeking behavior than symptoms themselves or physical health status. Bother scores may discriminate between those individuals with moderate symptoms (IPSS 8–19), who may be followed through watchful waiting instead of active therapy.

From pathogenesis to prevention of castration resistant prostate cancer

Significant progress in understanding the molecular basis of castration resistant prostate cancer (CRPCa) has been achieved in recent years. Despite this progress, CRPCa still remains a lethal disease. Early detection and prevention of CRPCa may provide a new strategy to improve survival of patients diagnosed with PCa at risk to fail standard androgen deprivation therapy (ADT).

Treatment of symptomatic benign prostatic hyperplasia with β-sitosterol: an 18-month follow-up

Objectives  To determine the long‐term effects of phytotherapy with β‐sitosterol (the trade name for β‐sitosterol used in this study is Harzol®) for symptomatic benign prostatic hyperplasia (BPH).

Management of the BPH Syndrome in Germany: Who Is Treated and How?

Objectives: To review the available data on contemporary management of symptomatic benign prostatic hyperplasia (BPH) within the German healthcare system. Methods: Information was obtained from articles published in scientific journals retrieved through searches in Medline and Embase. In addition, preliminary data from the first representative German survey on lower urinary tract symptoms (LUTS) were obtained (‘Herner LUTS-Study’, a community-based survey in Herne, a city within the industrial complex called the Ruhr Area). Finally, the recently established German guidelines for the diagnosis and treatment of the BPH-Syndrom (BPS) were reviewed. Results: Only few studies are published in the literature analysing the current concepts of management of BPH in Germany. These studies show that there is variation in the concepts of conservatory and surgical management of BPH. The German BPH guidelines suggest watchful waiting for patients with mild LUTS (total I-PSS ≤7) and medical therapy or surgery for those with moderate to severe LUTS (I-PSS >7). There was no final consensus on the role of phytotherapy in the German treatment guidelines, due to the lack of clinical data. α1-Blockers and finasteride (for prostates >40 ml) are recommended medical treatment approaches. Transurethral resection of the prostate (TUR-P) is considered to be the standard surgical procedure. Preliminary data from the Herner LUTS-Study show, that approximately 30% of men aged 50–80 years have moderate to severe LUTS (i.e. total I-PSS score >7). About a third of these men currently seek healthcare. Conclusions: LUTS and BPS are a highly prevalent condition in Germany. With the estimate that the number of men over the age of 65 will almost double in Germany within the next 30 years, it will be a challenge in the next millennium to find the healthcare resources for the management of BPS.

Prospective, Randomized, Multinational Study of Prostatic Urethral Lift Versus Transurethral Resection of the Prostate: 12-month Results from the BPH6 Study

BACKGROUND Transurethral resection of the prostate (TURP) is considered the gold standard for male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, TURP may lead to sexual dysfunction and incontinence, and has a long recovery period. Prostatic urethral lift (PUL) is a treatment option that may overcome these limitations. OBJECTIVE To compare PUL to TURP with regard to LUTS improvement, recovery, worsening of erectile and ejaculatory function, continence and safety (BPH6). DESIGN, SETTING, AND PARTICIPANTS Prospective, randomized, controlled trial at 10 European centers involving 80 men with BPH LUTS. INTERVENTION PUL or TURP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The BPH6 responder endpoint assesses symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation, and safety. Noninferiority was evaluated using a one-sided lower 95% confidence limit for the difference between PUL and TURP performance. RESULTS AND LIMITATIONS Preservation of ejaculation and quality of recovery were superior with PUL (p<0.01). Significant symptom relief was achieved in both treatment arms. The study demonstrated not only noninferiority but also superiority of PUL over TURP on the BPH6 endpoint. Study limitations were the small sample size and the inability to blind participants to enrollment arm. CONCLUSIONS Assessment of individual BPH6 elements revealed that PUL was superior to TURP with respect to quality of recovery and preservation of ejaculatory function. PUL was superior to TURP according to the novel BPH6 responder endpoint, which needs to be validated in future studies. PATIENT SUMMARY In this study, participants who underwent prostatic urethral lift responded significantly better than those who underwent transurethral resection of the prostate as therapy for benign prostatic hyperplasia with regard to important aspects of quality of life. TRIAL REGISTRATION ClinicalTrials.gov NCT01533038.

Prostate size and PSA serum levels in male patients with spinal cord injury

OBJECTIVES To evaluate prostate size and serum prostate-specific antigen (PSA) levels in male patients with spinal cord injury (SCI). As a result of improved medical care, the life expectancy in patients with SCI today equals the life expectancy of the general population. Therefore, male patients with SCI are likely to develop benign prostatic hyperplasia or prostate cancer. Although animal experiments indicate that neurogenic factors play an important role in prostate growth, the influence of these factors is not well examined in humans. METHODS The data of 100 male patients with SCI and 575 noninjured men were evaluated. The inclusion criteria were age older than 35 years and SCI for longer than 2 years. The exclusion criteria were previous prostate surgery, acute urinary tract infection, and bladder or prostate cancer. PSA was measured by an immunoenzymatic assay, and the prostatic volume was assessed by transrectal ultrasonography. For analysis, patients were grouped according to age. RESULTS With increasing age, the mean prostate volume increased in the patients with SCI and in the control group. The mean PSA level increased with age in the control group and to a far lesser extent in the patients with SCI. Neither for the entire cohort nor for the subgroups delineated by age were the differences in mean PSA level and mean prostate volume between patients with SCI and the control group statistically significant. CONCLUSION Prostate growth is detectable in patients with SCI. Although there is a tendency toward a lower prostate volume and lower serum PSA level in patients with SCI, the differences were not statistically significant. According to our results, the reference ranges for PSA levels are not vastly different from the general reference ranges.

Nocturia: state of the art and critical analysis of current assessment and treatment strategies

This editorial of the topic issue of the World Journal of Urology provides a state of the art on nocturia which includes descriptions of the terminology, epidemiology, health-related quality of life, medical and financial consequences, pathophysiology, assessment tools and treatment strategies of nocturia. This summary also includes a flowchart on the pathophysiology of nocturia with illustration of the various causes of reduced bladder capacity, increased fluid intake or increased diuresis; a flowchart with the key findings of frequency–volume charts to determine the underlying pathophysiology; and a flowchart on the treatment of the various causes of nocturia. The editorial critically discusses current assessment and treatment strategies in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and nocturia. The outcome of nocturia remains hidden in drug trials of patients with LUTS/BPH because nocturia-specific measures were not included. The authors recommend using frequency–volume charts, measurement of the hours of undisturbed sleep, and nocturia-specific quality of life questionnaires (e.g., ICIQ-N or N-Qol) in all future studies in patients with LUTS/BPH and nocturia.

Expert opinion on 6-monthly luteinizing hormone-releasing hormone agonist treatment with the single-sphere depot system for prostate cancer

Claude Schulman, Antonio Alcaraz*, Richard Berges†, Francesco Montorsi‡, Pierre Teillac¶ and Bertrand Tombal§ Departments of Urology, University Clinics of Brussels, Erasme Hospital, Brussels, Belgium, *Hospital Clinic, Fundacio Puigvert, Barcelona, Spain, †PAN-Clinic in Cologne, Germany, ‡Universita¢ Vita Salute San, Raffaele, Milan, Italy, ¶Saint-Louis Hospital, Paris, France and §Université Catholique de Louvain, Cliniques universitaires Saint Luc, Brussels, Belgium

[Phytotherapy of benign prostatic hyperplasia. Current evidence-based evaluation].

ZusammenfassungTrotz traditioneller Popularität als Arzneimittel in vielen Ländern Europas und trotz wachsender Beliebtheit als “Nahrungsmittelzusatz” in den USA bleibt die Rolle der Phytotherapie für LUTS (Lower Urinary Tract Symptoms) und benigner Prostatahyperplasie (BPH) umstritten. Legt man evidenzbasierte Kriterien an, zeigen nur wenige randomisierte Studien ohne ausreichend langes Follow-up sowie einige Metaanalysen vornehmlich über Serenoa repens und Pygeum Africanum sowie jüngste Studien mit Kürbiskernen einen klinischen Effekt bei guter Verträglichkeit. Umso mehr sind randomisierte, placebokontrollierte Studien erforderlich, um die tatsächliche therapeutische Potenz der einzelnen Präparate einzuordnen.AbstractDespite its popularity as a medication in various European countries or as a nutritional supplement in the United States, the role of plant extracts for the treatment of LUTS due to BPH remains controversial. Only a few randomized clinical trials that meet standard criteria of evidence-based medicine but with relatively short follow-up times and some meta-analyses mainly regarding Serenoa repens and Pygeum Africanum as well as more recent studies on pumpkin seeds have shown clinical effects and good tolerability. To better judge the therapeutic potential of these plant extracts, additional randomized placebo-controlled clinical trials with sufficient follow-up are needed.