Reginald C. Bruskewitz

The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia

Background Finasteride is known to improve urinary symptoms in men with benign prostatic hyperplasia, but the extent to which the benefit is sustained and whether finasteride reduces the incidence of related events, including the need for surgery and the development of acute urinary retention, are not known. Methods In this double-blind, randomized, placebo-controlled trial, we studied 3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands who were treated daily with 5 mg of finasteride or placebo for four years. Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence of outcome events were assessed every four months in 3016 men. Prostate volume was measured in a subgroup of the men. Complete data on outcomes were available for 2760 men. Results During the four-year study period, 152 of the 1503 men in the placebo group (10 percent) and 69 of the 1513 men in the finasteride group (5 percent) underwent surgery for benign prostatic hyperplasia (reduction in risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65 percent). Acute urinary retention developed in 99 men (7 percent) in the placebo group and 42 men (3 percent) in the finasteride group (reduction in risk with finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent). Among the men who completed the study, the mean decreases in the symptom score were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001). Treatment with finasteride also significantly improved urinary flow rates and reduced prostate volume (P<0.001). Conclusions Among men with symptoms of urinary obstruction and prostatic enlargement, treatment with finasteride for four years reduces symptoms and prostate volume, increases the urinary flow rate, and reduces the probability of surgery and acute urinary retention.

The effect of finasteride in men with benign prostatic hyperplasia

Background Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. Methods In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. Results As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. Conclusions The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

SERUM PROSTATE SPECIFIC ANTIGEN IS A STRONG PREDICTOR OF FUTURE PROSTATE GROWTH IN MEN WITH BENIGN PROSTATIC HYPERPLASIA

PURPOSE We analyze patterns of prostate growth in men diagnosed with benign prostatic hyperplasia (BPH) and treated with placebo during 4 years, and determine which baseline parameters were the strongest predictors of growth. MATERIALS AND METHODS A total of 3,040 men were enrolled in the 4-year randomized, placebo controlled Proscar Long-Term Efficacy and Safety study. Of these men a subgroup of 10% underwent pelvic magnetic resonance imaging prostate volume measurement at baseline and yearly thereafter. Absolute and percent volume changes during 4 years were calculated in the 164 placebo treated men in the subgroup. The ability of age, baseline prostate volume and prostate specific antigen (PSA) to predict prostate growth in placebo treated patients was assessed by multiple linear regression analyses, receiver operator characteristics curves, and evaluations of growth stratified by tertiles of baseline serum PSA and decades of life. RESULTS In placebo treated patients a steady increase in mean plus or minus standard deviation prostate volume from year to year was noted (2.5+/-6.1, 4.9+/-6.8, 6.4+/-8.5 and 7.2+/-8.8 ml. at years 1, 2, 3 and 4, respectively). Mean volume changes at 4 years ranged from -9 to +30 ml. Mean percent change from baseline ranged from 12.5% to 16.6% for men 50 to 59 years old to those 70 to 79 years old. Baseline serum PSA was a strong predictor of growth with 7.4% to 22.0% change at 4 years from the lowest to highest PSA tertiles. Annualized growth rates from baseline were 0.7 ml. per year for PSA 0.2 to 1.3, 2.1 for PSA 1.4 to 3.2 and 3.3 for PSA 3.3 to 9.9 ng./ml. Multiple linear regression analysis showed that serum PSA was a stronger predictor of prostate growth than age or baseline prostate volume. All but 1 man with baseline serum PSA greater than 2.0 ng./ml. had prostate growth during 4 years, and 32.6% of men with serum PSA less than 2.0 exhibited a decrease in volume. CONCLUSIONS Serum PSA is a stronger predictor of growth of the prostate in placebo treated patients than age or baseline prostate volume. Since prostate volume is a risk factor for acute urinary retention and the need for BPH related surgery, the ability of PSA to predict prostate growth may be an important factor when considering individual treatment options for BPH. Such use of PSA represents a shift in paradigm away from focusing solely on symptoms of BPH toward a more comprehensive approach with consideration of predicting and preventing risk factors of BPH related outcomes.

The Effect of Finasteride in Men with Benign Prostatic Hyperplasia

BACKGROUND Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. METHODS In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. RESULTS As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. CONCLUSIONS The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

3-Year Followup of Urinary Symptoms after Transurethral Resection of the Prostate

A total of 84 patients underwent detailed symptom analysis and urodynamic study preoperatively, and 3 and 12 months after transurethral resection of the prostate. In addition, 69 patients were contacted 3 years postoperatively for a detailed symptom analysis. These 3-year data then were compared to earlier evaluations. At 3 years 75 per cent of the patients claimed to have improvement, while 13 per cent stated that they were the same symptomatically. At the 1-year evaluation 84 per cent of the patients believed that they were improved and 10 per cent stated that they were unchanged. At 3 years 18 per cent of the patients had urge incontinence (an increase from 6 per cent at 1 year), while none complained of marked nocturia or frequency. Mean total irritative and obstructive symptoms were minimal and unchanged from the 1-year evaluation. Of the patients 33 per cent noticed decreased or absent erections and most blamed the surgery. One patient required another prostatic resection, while stricture developed in 3 and bladder neck contracture occurred in 6. We conclude that prostatic resection results in reasonable 3-year symptomatic improvement but it is hampered by other complications, including bladder neck contracture and, possibly, impotence.

5-YEAR OUTCOME OF SURGICAL RESECTION AND WATCHFUL WAITING FOR MEN WITH MODERATELY SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA: A DEPARTMENT OF VETERANS AFFAIRS COOPERATIVE STUDY

PURPOSE We determine outcomes after 5 years of followup for men who were randomized to receive transurethral resection or watchful waiting for moderate symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS A total of 556 patients were evaluated up to 60 months after randomization providing 966 patient-years of followup for transurethral prostatic resection and 990 for watchful waiting. Patients randomized to watchful waiting were evaluated according to whether they remained on treatment or crossed over to surgery. Outcomes included treatment failure, a genitourinary symptom score, peak flow rate, post-void residual urine volume and the degree of bother from genitourinary symptoms. RESULTS All outcomes were significantly better for transurethral prostatic resection than for watchful waiting. Treatment failure rates were 10% for transurethral prostatic resection versus 21% for watchful waiting (p = 0.0004). The crossover rate at 5 years was 36% and was positively associated with the degree of bother. Men with low pretreatment peak flow rates who were randomized to transurethral prostatic resection had 85% greater improvement in peak flow rate than comparable men who were randomized to watchful waiting and eventually crossed over to resection. However, after crossover, bother from genitourinary symptoms was similar to that of the resection group. CONCLUSIONS For men with moderate symptoms of benign prostatic hyperplasia transurethral prostatic resection has more favorable outcomes up to 5 years of followup compared to watchful waiting. While many men do well on watchful waiting, those who undergo transurethral prostatic resection after a trial of watchful waiting have less improvement in measures of bladder function than men randomized to resection, although there is no difference in serious adverse outcomes or bother from genitourinary symptoms.

Correlation of the American urological association symptom index with self-administered versions of the Madsen-Iversen, Boyarsky and Maine medical assessment program symptom indexes

We correlated the American Urological Association (AUA) symptom index with other indexes that have been used to measure symptoms for benign prostatic hyperplasia (BPH) and compared their psychometric properties. A self-administered questionnaire that allowed derivation of AUA, Maine Medical Assessment Program, Madsen-Iversen and Boyarsky symptom scores was completed by 76 men with clinically defined BPH, 59 younger control subjects, and 27 men before and after prostatectomy. The scores from the 4 indexes were strongly correlated (r = 0.77 to 0.93). All 4 indexes had good internal consistency and test-retest reliabilities. All indexes were predictive of patient global ratings of the degree of bother from the urinary condition. The AUA index discriminated BPH patients from controls significantly better than the Maine Medical Assessment Program index, and equivalently to the Madsen-Iversen and Boyarsky indexes (despite having fewer items). All 4 indexes were responsive when BPH patients underwent prostatectomy, although the AUA and Madsen-Iversen indexes were significantly more sensitive.

A PROSPECTIVE, RANDOMIZED 1-YEAR CLINICAL TRIAL COMPARING TRANSURETHRAL NEEDLE ABLATION TO TRANSURETHRAL RESECTION OF THE PROSTATE FOR THE TREATMENT OF SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA

PURPOSE We assess the 1-year efficacy and safety of transurethral needle ablation of the prostate compared to transurethral resection of the prostate for the treatment of symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS A prospective, randomized clinical trial of 121 men 50 years old or older with symptomatic BPH was performed at 7 medical centers across the United States. Of the men 65 (54%) were treated with transurethral needle ablation of the prostate and 56 (46%) underwent transurethral resection of the prostate. Mean and percentage changes from baseline and between cohorts for American Urological Association (AUA) symptom score, AUA bother score, quality of life score, peak urinary flow rate and post-void residual urine volume were measured at 1, 3, 6 and 12 months following treatment. Length of procedure, hospitalization, type of anesthesia, post-procedure catheterization, side effects and sexual function were compared. RESULTS Transurethral needle ablation and resection resulted in a statistically significant improvement in AUA symptom, bother and quality of life scores, peak urinary flow rate and post-void residual. At 1-year followup, needle ablation and resection were equally effective in enhancing quality of life. Needle ablation had less effect on sexual function, with resection being associated with a greater incidence of retrograde ejaculation. Needle ablation could be performed as an outpatient procedure with local anesthesia while resection required anesthesia and hospitalization. Needle ablation was associated with markedly fewer side effects than resection. CONCLUSIONS Compared to transurethral resection of the prostate, transurethral needle ablation of the prostate is an efficacious, minimally invasive treatment for symptomatic BPH that is associated with few side effects.

Analysis of Presenting Symptoms in Prostatism

A prospective evaluation was done of 84 patients who were selected for transurethral prostatectomy based on the presenting symptoms and findings at cystoscopy. In addition, urodynamic studies were performed but the results were not made available to the urologist who selected the patients for surgery. Postoperative symptom analysis and repeat urodynamic examinations were done at 3 months in 68 patients and at 12 months in 50. There was no significant association between irritative symptoms and uninhibited detrusor contractions. Furthermore, no associations were identified between obstructive symptoms and infravesical obstruction as defined by urodynamic criteria. The study failed to identify a need for routine invasive urodynamic investigation of patients with benign prostatic hypertrophy.

Further Study of the Increased Mortality Following Transurethral Prostatectomy: A Chart-Based Analysis

Previous studies using large administrative databases found an elevated relative risk of reoperation and death after transurethral resection of the prostate compared to open prostatectomy. To investigate whether differences in case-mix unmeasured by administrative data explained this finding, we reviewed the charts of 485 patients who had undergone prostatectomy (236 open and 249 transurethral) at the Health Science Centre, Winnipeg, Manitoba, Canada between 1974 and 1980. Data from patient histories, physical examinations and laboratory evaluations were abstracted and used to control for case-mix in models comparing the rates of reoperation and mortality after transurethral versus open prostatectomy. Several models were specified. In all models the relative risk of dying after transurethral prostatectomy remained elevated (1.36 to 1.89), as did the risk for reoperation (3.62). A prospective trial is needed to establish the relative safety and effectiveness of transurethral and open prostatectomy.