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An update of a systematic review of alpha1-adrenoceptor (AR) antagonists in the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) showed that these agents have comparable efficacy. The total symptom score is improved by 30-45% and maximum urinary flow rate by 15-30% vs baseline. alpha1-AR antagonists that can be started at their therapeutic dose have a more rapid onset of action than alpha1-AR antagonists that have to be titrated. alpha1-AR antagonists can be differentiated according to their tolerability. Alfuzosin (especially the 10 mg once daily dose) and tamsulosin (especially the 0.4 mg once daily dose) are better tolerated than doxazosin and terazosin. However, alfuzosin might induce more cardiovascular adverse events (AEs) in the elderly and/or patients with cardiovascular comorbidity and/or comedication. Tamsulosin tends to interfere less with blood pressure regulation and induce less vasodilatory AEs than alfuzosin, especially in the elderly, and is well tolerated in patients with cardiovascular comorbidity and/or comedication. Cardiovascular AEs might lead to potentially serious complications such as falls, fractures and institutionalization. Abnormal ejaculation has mainly been reported in placebo-controlled trials with tamsulosin but in direct comparative trials its rate with tamsulosin 0.4 mg was similar to, or only slightly higher than, the rate with alfuzosin. In addition, abnormal ejaculation is not reported as bothersome by the patient or associated with serious complications. It can be concluded that an alpha1-AR antagonist with a low potential to interfere with blood pressure regulation and to induce cardiovascular AEs, also in patients with cardiovascular comorbidity and/or comedication, can be considered a first-choice treatment option in LUTS/BPH.

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Dutasteride is a new dual 5alpha-reductase inhibitor for the treatment of benign prostatic hyperplasia. It differs from finasteride as it inhibits both isoenzymes of 5alpha-reductase and results in near-complete suppression of serum dihydro-testosterone. Similar to finasteride, it reduces serum prostatic specific antigen by approximately 50% at 6months and total prostate volume by 25% in 2years. Randomised, placebo-controlled trials conducted over 2years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and the need for surgery. The main side effects are erectile dysfunction, decreased libido, gynaecomastia and ejaculation disorders. However, long-term usage for > 4years did not reveal increased new onset of sexual side effects. In addition, the combination of dutasteride and tamsulosin is well-tolerated and has the added advantage of rapid symptomatic relief. Finally, dutasteride has been shown to possess tumour regression properties invitro and its role in chemoprevention of prostate cancer will be confirmed in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

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Biochemical parameters and pathological features as well as biopsy related morbidity of prostate cancer detected on second, third and fourth repeat prostate biopsy in men with a serum total PSA level between 4 ng/mL and 10 ng/mL were evaluated and compared to those cancers detected on initial prostate biopsy. In a prospective European Prostate Cancer Detection study, 1051 men with a total PSA level between 4 ng/mL and 10 ng/mL underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a first repeat biopsy after 6 weeks. If also negative a third and even a fourth biopsy was performed at 8 weeks intervals. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. Cancer detection rates on first, second, third and fourth biopsy were 22% (231/1051), 10% (83/820), 5% (36/737) and 4% (4/94), respectively. Percent free PSA and PSA-TZ were the most powerful parameters to predict cancer on repeat biopsy. Overall, of patients with clinically localized disease (67% of cancers detected), 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% had organ confined disease on first, repeat, third and fourth biopsy, respectively. Despite statistical significant differences with respect to multifocality (p=0.009) and cancer location (p=0.001) (cancers on second biopsy showing a lower rate of multifocality and a more apico-dorsal location), there were no differences with respect to stage (p=0.2), Gleason score (p=0.3), percentage Gleason grade 4/5 (p=0.2), serum PSA and patient age between first and second biopsy. However, cancers detected on third and fourth biopsy had a significantly lower Gleason score (p=0.001 and 0.001), lower rate of grade 4/5 cancer (p=0.02), lower cancer volume (p= 0.001 and 0.001) and lower stage (p= 0.001). Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Interestingly, patients under 60 years of age reported a higher pain apprehension as quantified with the visual analog pain scale (VAS). Further, the use of the Vienna tables allowed an accurate calculation of the number of biopsy cores required based on prostate volume and age. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and second biopsy were similar, suggesting similar biological behavior. Cancers detected on third and fourth biopsy had a lower grade, stage and cancer volume as compared to cancers on first and repeat biopsy. Morbidity of first and repeat biopsy were similar, whereas third and fourth biopsy had a slightly higher complication rate. Hence, a second prostate biopsy in all cases of a negative finding on initial biopsy appears justified. Third and fourth repeat biopsies however, should only be obtained in very selected patients with high suspicion of cancer and/or poor prognostic factors on the first or second biopsy. Power Doppler TRUS will further enhance prostate cancer detection as will artificial neural networks as patient selecting tools.

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PURPOSE OF REVIEW: Prevalence of benign prostatic hyperplasia (BPH) is increasing with the aging population worldwide. Knowledge of the natural history of BPH is crucial for primary, secondary and tertiary prevention of its progression. This review examines the evidence of the natural history of BPH, highlighting the group of patients with mild symptoms and the risk factors for progression. RECENT FINDINGS: Several community and clinical studies have demonstrated the progressive nature of BPH. Different surrogate endpoints, which include symptom score, peak urinary flow rate, prostate volume, and the occurrence of acute urinary retention and need for surgery, have been described. Prostatic specific antigen and prostate volume are the two most common predictors of clinical progression and are helpful to the clinician for identifying high-risk patients. SUMMARY: With further understanding of the natural history and the predictors of progression of BPH, management can be better tailored according to risk stratification and the results of clinical trials of effectiveness can be better interpreted.

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PURPOSE OF REVIEW: Serenoa repens extract is a popular phytotherapeutic agent in men with lower urinary tract symptoms. Although the exact mechanism of action is unknown, the agent is generally well accepted for its easy availability and good tolerability. This paper reviews the evidence of its efficacy in comparison with placebo, 5-alpha reductase inhibitor and alpha-1 adrenoreceptor antagonist. RECENT FINDINGS: Serenoa repens extract is comparable with 5-alpha reductase (finasteride) and alpha-1 antagonist in the treatment of benign prostatic hyperplasia in terms of symptom score and peak urinary flow rate improvement, but has a lower incidence of associated sexual dysfunction. Furthermore, long-term usage (36 months) of Serenoa repens decreases the progression rate of the condition as compared with watchful waiting. In addition, the efficacies of Serenoa repens are proven in several placebo-controlled trials. SUMMARY: Serenoa repens has proven its role in the management of benign prostatic hyperplasia and will remain as a viable first-line treatment option.

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OBJECTIVES: To determine the risk of clinical progressions in men with mild lower urinary tract symptoms of bladder outlet obstruction and identify the predictors for progression in this group of men. METHODS: A total of 397 men who presented to the urology clinics with mild symptoms of bladder outlet obstruction (International Prostate Symptom Score less than 8) were analyzed in this longitudinal study conducted during a 4-year period. They began with the watchful waiting protocol and were followed up every 3 months for 48 months. Age, International Prostate Symptom Score (IPSS), divided into obstructive symptom score and irritative symptom score, serum prostate-specific antigen level, total prostate volume, transitional zone volume, urinary flow rates, and postvoid residual urine volume were documented. RESULTS: The cumulative incidence of clinical progression, defined as worsening of the IPSS with migration to the moderate symptom group (IPSS 8 to 18) or severe symptom group (IPSS 19 to 35) and an increase in IPSS of more than 2 points, was 6%, 13%, 15%, 24%, 28%, and 31% at 6, 12, 18, 24, 36, and 48 months, respectively. Nineteen patients (4.9%) developed acute urinary retention within the 48-month follow-up period. Of these 19 patients, only 2 (0.6%) required transurethral resection of the prostate. The variables of importance for disease progression in the artificial neural network analysis were, in order of statistical significance, prostate-specific antigen level, obstructive symptom score, and transitional zone volume. CONCLUSIONS: The risk for men with mild symptoms of bladder outlet obstruction to progress clinically and develop complications such as acute retention of urine is moderate. Prostate-specific antigen, obstructive symptom score, and transitional zone volume were identified as important risk factors.

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