Accuracy and repeatability of prostate volume measurements by transrectal ultrasound.

We evaluated six alternative methods of prostate volume determination by transrectal ultrasound, three based on planimetry and three based on measurement of prostate diameters. Prostate volume measurements were made on an average of 6.5 occasions over a 3 y period on 41 patients with benign prostatic hyperplasia, using standard techniques. We defined the average of multiple planimetries as the prostate reference volume. Agreement with the reference volume and reproducibility at repeat testing was in the same range for single planimetry and volume determinations based on the formulas height (H) x width (W) x length (L) x pi/6 and W x W x H x pi/6, but was poorer using the formula W x W x W x pi/6. Using the average result of two successive planimetry measurements increased the reproducibility of planimetry, being statistically significantly better than for one single planimetry (P=0.024) or for the formula W x W x H x pi/6 (P=0.048). Our study suggests that the simple formula based methods of prostate volume determination provide results that are only marginally inferior to one single planimetry, but results are improved by performing two planimetry measurements.

Treatment of benign prostatic hyperplasia. A pharmacoeconomic perspective.

Men with moderate symptoms of benign prostatic hyperplasia (BPH) are the best candidates for medical treatment, while surgery is usually indicated for patients with severe symptoms. Men with mild symptoms do not usually need treatment, but they might be re-evaluated annually if desirable. Finasteride, which produces selective hormonal deprivation, is now established as a well tolerated drug for the long term medical therapy of BPH. Recent studies suggest that finasteride is most effective in men with large prostates (> 40 ml), and the drug should probably be reserved for these patients. alpha-Blockers work in men with small or large prostates, and their rapid onset of action facilitates the identification of responders. alpha-Blockers are more effective than finasteride during the first year of treatment, but only finasteride induces regression of the prostate and offers increased efficacy over time. Even if drug therapy reduces the need for prostate surgery, the total economic cost of BPH treatment is likely to rise because of the increasing application of medical treatment. The magnitude of this increase depends largely on what percentage of the male population embark on long term therapy, at what age treatment is started, and how successful it is. At present, the answers to these questions are largely unknown. The personal economic expenses for men who begin long term medical therapy will probably be an important factor in deciding how common drug treatment for BPH will become in the future. For many men, the main benefit of drug treatment will be the relief of urinary symptoms, but whether this improvement is substantial enough to improve their overall quality of life has not yet been clearly demonstrated in controlled studies.

Complications of invasive, urodynamic examinations and prostate biopsies in patients with benign prostatic hyperplasia.

We studied 85 men with moderate to severe symptoms of benign prostatic hyperplasia (BPH) who completed two placebo-controlled studies of drug therapy. During the 48 week period of treatment and follow-up the patients underwent 164 procedures which included urethral instrumentation, predominantly without antibiotic prophylaxis, and 187 procedures of urethral instrumentation in combination with transperineal prostate biopsy with antibiotic prophylaxis. The risk for a patient to acquire clinically significant urinary tract infection was 2.4% after urethral instrumentation alone and 7.5% when urethral instrumentation was combined with prostate biopsy. Invasive urodynamic examinations of prostate biopsies in studies of new treatment modalities for BPH should only be performed when necessary to obtain important information, and after full informed patient consent. The combination of prostate biopsy and urethral instrumentation increases the infection rate considerably and should be avoided.

Morphometry of benign prostatic hyperplasia during androgen suppressive therapy. Relationships among epithelial content, PSA density, and clinical outcome.

We performed light microscopic morphometry on prostate biopsies of 41 patients who underwent androgen suppressive therapy for 24 weeks with the luteinizing hormone releasing hormone (LHRH) agonist leuprolide depot for symptomatic benign prostatic hyperplasia (BPH). Before treatment started, the prostates consisted of 88.4% stroma, 9.0% epithelium and 2.6% glandular lumen. After completion of therapy, the percentages were 94.7, 3.0 and 2.3, respectively. The absolute reductions of volume were 27% for stroma, 77% for epithelium and 40% for lumen. Correlations between pretreatment parameters (epithelial content, stromal epithelial ratio and prostate specific antigen density (PSAD)) and the clinical outcome parameters (prostate volume reduction, improvement in maximum flow rate, reduction of symptom score and reduction in outflow resistance) were not statistically significant, indicating that the histological composition of BPH tissue or PSAD are poor parameters to predict differences in response for individual patients during hormonal therapy for BPH. By comparing morphometry results of the core biopsies with morphometry performed on corresponding TURP tissue, it appeared that the lumen content of the biopsies was somewhat underestimated.

A prospective, placebo-controlled study of the luteinizing hormone-releasing hormone agonist leuprolide as treatment for patients with benign prostatic hyperplasia.

Several physicians have used luteinizing hormone-releasing hormone agonists for small, selected groups of patients with benign prostatic hyperplasia but their clinical role in this indication is still not well defined. We investigated the effect of the luteinizing hormone-releasing hormone agonist leuprolide given as an injection every 28 days for 24 weeks in a double-blind, placebo-controlled trial with 50 evaluable patients along an extensive protocol with the main emphasis on objective parameters for outcome assessment. Prostate volume decreased by 34.5% (2.6% in the placebo group). Maximum flow rate at spontaneous micturition and after instillation of saline improved by 2.0 ml. per second (32%) and 3.0 ml. per second (54%) more than with placebo. Detrusor pressure during micturition decreased by approximately 24% for patients who received leuprolide compared to placebo and was accompanied by a 25% increase in flow rate, which indicated decreased bladder outlet resistance. Improvement in urodynamic parameters generally was of statistical significance. Symptom scores improved significantly for both groups throughout the study when compared to those before treatment. At between group comparison, the improvement for irritative symptoms in favor of leuprolide reached statistical significance at week 48. With few exceptions, leuprolide patients tolerated the treatment well even if they had side effects, such as flushing and decreased sexual function.

Safety, side effects and patient acceptance of the antiandrogen Casodex in the treatment of benign prostatic hyperplasia.

Casodex, a new nonsteroidal antiandrogen, was investigated in this double-blind, randomized, placebo-controlled study comprising 28 evaluable patients with benign prostatic hyperplasia, who received Casodex at a dosage of 50 mg daily or a placebo for 24 weeks. The good safety profile of Casodex was confirmed. In common with other nonsteroidal antiandrogens, Casodex was associated with breast enlargement and/or tenderness, being reported by all patients upon direct questioning. A change in sexual function was assessed by two questionnaires, one of them revealing no statistically significant difference between the groups. However, using an alternative questionnaire, approximately half of the patients reported reduced erectile function (p = 0.002), mostly partial, and reduced sexual activity (p = 0.015), whereas libido was well maintained when compared to the placebo. Casodex was not associated with hot flushes. No other side effects of clinical significance were seen, and Casodex was well tolerated by the majority of the patients.

Measuring the quality of life of patients with benign prostatic hyperplasia. Assessment of the usefulness of a new quality of life questionnaire specially adapted to benign prostatic hyperplasia patients.

A questionnaire consisting of 36 questions based on a visual analogue scale for measuring the quality of life (QOL) of benign prostatic hyperplasia (BPH) patients is presented and assessed. The sensitivity of the questionnaire is demonstrated by its ability to register a statistically significant (p less than 0.01) improvement of QOL after prostate surgery (transurethral resection of the prostate). Its reliability is shown by its ability to give reproducible results in a nonoperated BPH patient group. Patient compliance has been excellent. It is discussed to what extent questions directly concerning symptoms from prostatism should be included in QOL questionnaires for BPH patients. Nonparametric statistics are applied. It is concluded that questionnaires like this are useful tools in the assessment of BPH patients, irrespective of the treatment modality. They will probably be of particular value in studies of drug therapy of BPH, complementing methods of assessment like symptom score and urodynamic parameters.

alpha-blockade in the treatment of symptomatic benign prostatic hyperplasia.

PURPOSE: The clinical and urodynamic effects of oral alpha 1-selective adrenoceptor blockers in the treatment of symptomatic benign prostatic hyperplasia were quantified, and side effects and patient tolerance were assessed. MATERIALS AND METHODS: A total of 29 original reports of placebo controlled clinical trials of alpha-blockers in which results were adequately presented was identified and reviewed, along with additional pertinent literature. We assumed that the efficacy of the different alpha-blockers was basically the same and the weighted average treatment effect was calculated in comparison with placebo. RESULTS: The average improvement in maximum urine flow rate was 1.5 ml. per second but this rate would probably approach 1.8 to 1.9 ml. per second if all dosages had been titrated up to the highest level tolerated. Overall symptom score decreased by 14% and residual urine volume decreased by 29%. A slight decrease in detrusor pressure during voiding was suggested. CONCLUSIONS: alpha-Blockers were beneficial in the treatment of benign prostatic hyperplasia. Tolerance to treatment appeared to develop in a large proportion of patients after 6 months of therapy. However, for patients who benefit from long-term use of alpha-blockers effective treatment might be maintained for years.

Effects of the nonsteroidal antiandrogen Casodex on lipoproteins, fibrinogen and plasminogen activator inhibitor in patients with benign prostatic hyperplasia.

The effect of the nonsteroidal antiandrogen Casodex (176334) on a number of risk factors for cardiovascular diseases was investigated in a double-blind, randomized, placebo-controlled study comprising 27 evaluable patients with benign prostatic hyperplasia who received either placebo or Casodex at a dosage of 50 mg daily for 24 weeks. We hypothesized that the 30-35% increase in serum levels of testosterone and estradiol seen during treatment with Casodex might induce changes in various risk factors. We found no statistically significant change in total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. Apolipoproteins A1 and B also remained unchanged, along with plasma concentrations of fibrinogen and plasminogen activator inhibitor 1. Casodex has the potential to become an important drug for treatment of prostatic diseases. Our study does not suggest that the drug is associated with an increased cardiovascular risk.

A prospective, placebo-controlled study of the antiandrogen Casodex as treatment for patients with benign prostatic hyperplasia.

Casodex, a new nonsteroidal antiandrogen, is presently being investigated in phase III studies as a new hormonal treatment for advanced prostatic cancer. The safety and efficacy of Casodex at a dosage of 50 mg. daily for 24 weeks in patients with benign prostatic hypertrophy were investigated in this double-blind placebo-controlled trial, initially planned for 60 patients. Inclusion was discontinued at 30 patients after report of liver toxicity when Casodex was given long-term at high doses to mice. Prostate volume was decreased by 26.4% at the end of therapy (3.7% in the placebo group). The differences between Casodex and placebo therapy for the changes in values from baseline to 24 weeks of treatment in maximum urinary flow rate at spontaneous micturition and after instillation of saline were 0.8 and 1.4 ml. per second (not statistically significant). Pressure-flow examinations and frequency-volume charts did not show any treatment effect. Casodex patients tended to obtain more improvement in symptom scores than placebo patients, reaching statistical significance for irritative symptoms at week 24. Even if all patients had side effects, mostly mild, Casodex was well tolerated and patient compliance was excellent.

Patient recruitment to and cost of a prospective trial of medical treatment for benign prostatic hyperplasia.

409 consecutive patients, referred by general practitioners for assumed benign prostatic hyperplasia (BPH), were evaluated for inclusion into a hormone therapy trial for BPH. 97 patients were excluded initially. Upon examination of the 312 remaining patients, 221 were found to be ineligible for various reasons and 11 refused to participate. Other patients were excluded after a second, more extensive examination and 5 patients withdrew during the trial. We are now left with 66 patients (16.1% of the patients initially referred), of which approximately 33 are receiving placebo treatment. The financial costs for the hospital to carry out a drug trial with approximately 65 evaluable patients is estimated to exceed 40,000 pounds.

Can prostate epithelial content predict response to hormonal treatment of patients with benign prostatic hyperplasia?

OBJECTIVES: There are large interindividual differences in response to medical therapy for men with benign prostatic hyperplasia. Selection of patients for alpha-blocker versus hormonal treatment is often based more on assumptions than on well-documented knowledge. A more scientifically based decision of therapy has a potential for economical savings and increased effectiveness. METHODS: We performed morphometry on prostate biopsy specimens and determined the amount of stroma, epithelium, and glandular lumen (pretreatment characteristics) in 34 men with benign prostatic hyperplasia before 24 weeks of androgen suppressive therapy. Androgen suppressive therapy consisted of either the luteinizing hormone-releasing hormone agonist leuprolide depot (3.75 mg intramuscularly every 28 days) or the nonsteroidal antiandrogen bicalutamide (50 mg/day orally). The evaluation of the clinical response (effectiveness parameters) was based on changes in prostate volume, peak urinary flow rate, symptom score, and bladder outlet obstruction. RESULTS: A large prostate volume before treatment was associated with more pronounced symptom score improvement, but neither prostate-specific antigen nor any of the parameters of tissue composition used (percentage of epithelium, epithelial volume, and stromal/epithelial ratio) predicted a favorable response to hormonal treatment. CONCLUSIONS: The pretreatment variables that are readily available at present have a limited role in helping clinicians to decide the optimal medical treatment for patients with benign prostatic hyperplasia.

Safety, side effects and patient acceptance of the luteinizing hormone releasing hormone agonist leuprolide in treatment of benign prostatic hyperplasia.

The luteinizing hormone releasing hormone agonist leuprolide was investigated in a double-blind, randomized, placebo-controlled study comprising 50 evaluable patients with moderate to severe symptoms resulting from benign prostatic hyperplasia. Patients received 3.75 mg. leuprolide depot or placebo as an injection every 28 days for 24 weeks. Hemoglobin level decreased by 0.8 gm/100 ml. (p = 0.0052) for patients receiving leuprolide. Mean testicular volume decreased by 28.9% (p < 0.001) compared to placebo. Of 26 patients receiving leuprolide 5 had a weight gain of more than 3 kg. Almost all patients receiving leuprolide experienced hot flushes. Breast changes, and loss of energy and vigor were not more pronounced than for patients receiving placebo. Erectile function and sexual activity were lost during treatment. Libido also decreased but was still partially retained. Despite this, patients receiving leuprolide were generally contented with their sexual life during treatment. Side effects were bothersome for some patients but were reversible. Of the patients in our study 73% expressed that they could repeat or continue treatment if that had been possible. The high cost of these drugs will limit their use for a benign condition, such as benign prostatic hyperplasia.

[Timely screening routines for prostatic cancer by Norwegian physicians]. / Norske legers rutiner for opportunistisk screening for prostatakreft.

It has been claimed, though not scientifically proven, that early diagnosis and treatment of prostate cancer reduce cancer-related mortality. The aim of the present study is to assess the frequency of PSA-based screening in Norwegian primary health care. In 1998 Norwegian general practitioners and occupational physicians reported their use of diagnostic PSA (prostatic specific antigen) testing in men without urinary symptoms (opportunistic PSA screening). There were considerable variations between counties and an increasing tendency to screen 60% of physicians performed opportunistic PSA screening; however, 55% only "sometimes". Men over 75 were frequently tested. The results reflect the scientific uncertainty regarding opportunistic PSA screening. PSA screening as an element of health care policy can only be recommended if cancer-related mortality is reduced by early diagnosis and treatment of prostate cancer.

Effects of bicalutamide and leuprolide on prostate-specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP) in men with benign prostatic hyperplasia (BPH).

The effects of the nonsteroidal antiandrogen bicalutamide (Casodex(TM)) and the luteinizing hormone releasing hormone agonist leuprolide depot (Procren Depot(TM), Lupron Depot(TM)) on serum prostate-specific antigen (PSA), acid phosphatase (ACP), and prostatic acid phosphatase (PAP) in patients with benign prostatic hyperplasia (BPH) were determined. Thirty patients with BPH were randomised to receive bicalutamide 50 mg orally once daily or a placebo for 24 weeks, followed by 24 weeks of follow-up (bicalutamide study). In another study 55 men were randomised between 3.75 mg leuprolide depot intramuscularly at every 28 days for 24 weeks or placebo injections (leuprolide study). In both studies blood sampling was performed at baseline, at week 12 at week 24 and 24 weeks after the end of therapy. Androgen suppression with bicalutamide 50 mg daily for 24 weeks resulted in a median of 56% reduction of PSA (P<0.001 when compared to placebo). Acid phosphatase and PAP did not change. Leuprolide resulted in a median of 87% reduction of serum PSA (P<0.001) and a 39% reduction of PAP (P=0.023), whereas ACP was unchanged. Both bicalutamide and leuprolide induced a pronounced decline in serum PSA in BPH patients. The studies suggest a stronger androgen suppressive effect of leuprolide than of bicalutamide, but this difference might largely be due to too low a dosage of bicalutamide. ACP and PAP were relatively insensitive to androgen suppression. Our study suggests a different degree of androgen suppression on PSA originating from benign tissue versus cancer tissue, and that the direction of this discrepancy might be different for various androgen suppressive regimens.Prostate Cancer and Prostatic Diseases (2001) 4, 173-177.

Effects of the luteinizing hormone-releasing hormone agonist leuprolide on lipoproteins, fibrinogen and plasminogen activator inhibitor in patients with benign prostatic hyperplasia.

The impact of chronic administration of the luteinizing hormone-releasing hormone agonist leuprolide depot on cardiovascular risk factors was investigated in a controlled double-blind study comprising 50 evaluable patients with benign prostatic hyperplasia. In the 26 patients receiving leuprolide the mean total cholesterol level increased by 10.6%, high density lipoprotein cholesterol by 8.2% and triglycerides by 26.9% (p = 0.003, 0.052 and 0.050, respectively). Low density lipoprotein cholesterol levels were unchanged. Apolipoprotein A1 increased by 13.2% (p = 0.001), while apolipoprotein B, fibrinogen, thrombocytes and plasminogen activator inhibitor were unchanged. Hemoglobin decreased by 1.2 gm./100 ml. without a concomitant decrease in serum erythropoietin concentration. These changes act in different directions with regard to cardiovascular risk and the overall effect is difficult to assess.

Effects on the endocrine system of long-term treatment with the non-steroidal anti-androgen Casodex in patients with benign prostatic hyperplasia.

OBJECTIVE: To study the hormonal changes resulting from long-term use of the non-steroidal anti-androgen Casodex. PATIENTS AND METHODS: A randomized, placebo-controlled study was carried out on 27 patients with benign prostatic hyperplasia (BPH). Fourteen patients received Casodex 50 mg daily for 24 weeks and 13 received a placebo. The patients were followed up for a further 24-week period. RESULTS: Serum concentrations of luteinizing hormone (LH) increased by an average of 40% while follicle-stimulating hormone (FSH) remained unchanged. Testosterone increased by 35%, oestradiol by 29% and oestrone by 23%; all changes were statistically significant. Levels of androstenedione and dihydrotestosterone increased by 11% and 15%, respectively, but these increases did not reach statistical significance. A non-significant increase was also observed for sex hormone-binding globulin. The hormonal changes were reversible upon discontinuation of therapy. Prolactin and dehydroepiandrosterone-sulphate levels did not change. CONCLUSION: This study indicates that Casodex, due to competitive inhibition of central androgen receptors, increases LH secretion, thus causing increased production and increased metabolism of testosterone.

Effects on the endocrine system of long-term treatment with the luteinizing hormone-releasing hormone agonist leuprolide in patients with benign prostatic hyperplasia.

Hormonal changes resulting from long-term use of the luteinizing hormone-releasing hormone agonist leuprolide depot were studied in a randomized placebo-controlled study comprising 50 evaluable patients with benign prostatic hyperplasia (BPH). A total of 26 patients received 3.75 mg leuprolide depot intramuscularly every 28 days for 24 weeks and 24 received a placebo. The patients were followed up for a further 24-week period. Serum concentrations of luteinizing hormone decreased by 90% and follicle-stimulating hormone by 55% during the treatment period. Mean testosterone levels decreased by 96% to 0.7 nmol l-1 and dihydrotestosterone decreased by 90%. The adrenal androgens androstenedione and dehydroepiandrosterone sulphate decreased by 48 and 24%, respectively. In most patients, estradiol decreased to non-detectable values, while the decrease in estrone was 35%. There was no change in prolactin and sex hormone-binding globulin as compared to the placebo group. Hormonal changes were reversible, but the suppression of testicular hormone production was not completely normalized in all patients 24 weeks after discontinuation of the treatment.