Serial prostate-specific antigen measurements in men with clinically benign prostatic hyperplasia during a 12-month placebo-controlled study with terazosin. HYCAT Investigator Group. Hytrin Community Assessment Trial.

OBJECTIVES: To prospectively analyze whether the treatment of men with clinically benign prostatic hyperplasia (BPH) with alpha blocking agents affects the serum prostate-specific antigen (PSA) levels, and to determine the magnitude of such effect. METHODS: Serial PSA measurements were performed using the Abbott IMx assay over 1 year in 134 men over the age of 55 years participating in the Hytrin Community Assessment Trial (HYCAT). HYCAT is a 1-year, randomized, placebo-controlled, double-blinded study of the alpha1-adrenergic antagonist terazosin. All men had lower urinary tract symptoms and a clinical diagnosis of BPH with an American Urological Association (AUA) symptom index of 13 points or more, an AUA bother score of 8 points or more, and a peak urinary flow rate of less than 15 mL/s. PSA was measured at baseline and at 8, 26, 39, and 52 (end of study) weeks. RESULTS: Baseline serum PSA levels weakly correlated with patients' age at study entry, and modestly with residual urine (positive correlation) and peak flow rate (negative correlation), although none of the levels were statistically significant. Changes of serum PSA during the course of the study did not correlate with either one of the symptom severity or bother assessment tools, residual urine, or peak flow rate. Mean PSA increased from a baseline of 2.5+/-0.22 ng/mL (mean+/-SE) by 0.5+/-0.11 ng/mL in the placebo-, and from 2.7+/-0.23 ng/mL by 0.3+/-0.11 ng/mL in the terazosin-treated patients (P = 0.36 by ANOVA). There were no differences in the changes in serum PSA when patients were stratified by decade of life according to the age-specific PSA reference ranges, or by the final dose of terazosin (2, 5, or 10 mg daily). CONCLUSIONS: The treatment of men with lower urinary tract symptoms and clinical BPH with the alpha1-adrenergic antagonist terazosin does not affect serum PSA concentration, and thus does not confound longitudinal monitoring of serum PSA levels in patients at risk for prostate carcinoma.

The Hytrin Community Assessment Trial study: a one-year study of terazosin versus placebo in the treatment of men with symptomatic benign prostatic hyperplasia. HYCAT Investigator Group.

OBJECTIVES: To determine the clinical effectiveness and safety of alpha(1)-blockade therapy versus placebo in the treatment of men with moderate to severe symptoms of prostatism in a community-based population under usual care conditions. METHODS: The Hytrin Community Assessment Trial is a prospective, placebo-controlled, randomized, double-blinded, 1-year clinical trial, conducted at 15 academic medical centers (regional sites) and 141 private urology practices (satellite sites). A total of 2084 men at least 55 years old with moderate to severe symptoms of benign prostatic hyperplasia (BPH) as determined by an American Urological Association (AUA) Symptom Score (AUA-SS) of 13 or more points and a bother score (AUA-BS) of 8 or more were enrolled. Randomized patients at regional sites were required to have a peak urinary flow rate less that 15 mL/s with voided volume of at least 150 mL. Treatment with terazosin was initiated with 1 mg daily for 3 days, followed by 2 mg daily for 25 days. Thereafter, patients were titrated stepwise to 5 or 10 mg if they failed to achieve a 35% or greater improvement in the AUA-SS. Primary outcome measures were AUA-SS, AUA-BS, BPH Impact Index (BII), disease-specific quality of life (QQL) score, and treatment failure as defined as discontinuation due to persistent or worsening symptoms or need for surgical intervention for BPH. Secondary outcome measures were peak urinary flow rate and postvoid residual urine volume. RESULTS: AUA-SS (0 to 35 point scale) improved from a baseline mean of 20.1 points by 37.8% during terazosin (n=976) and by 18.4% during placebo (n=973) treatment (P<0.001). Similarly, statistically superior improvements were observed in regard to the AUA-BS, BII, and the QQL score in the terazosin-treated patients. Peak urinary flow rate improved from a baseline of 9.6 mL/s (both regional treatment groups) by 2.2 mL/s in the terazosin group (n=137) and by 0.7 mL/s in the placebo group (n=140) (P< or = 0.05). Treatment failure occurred in 11.2% of terazosin- and 25.4% of placebo-treated patients (P<0.001; Kaplan-Meier adjusted withdrawal rates of 365 days). Withdrawal from study drug treatment due to adverse events occurred in 19.7% of terazosin- and 15.2% of placebo-treated patients (P<0.001). CONCLUSIONS: Terazosin given once daily in a dose ranging from 2 to 10 mg in community-based urology practices under conditions simulating usual care is effective in reducing the symptoms, perception of bother, and the impairment of QQL due to urinary symptoms in men with moderate to severe symptoms of prostatism. This effect is superior to placebo and maintained over 12 months of follow-up. Clinical research outcome studies in BPH can be conducted in community-based practices, thus simulating as closely as possible "usual care" conditions.

The cost-effectiveness of terazosin and placebo in the treatment of moderate to severe benign prostatic hyperplasia.

OBJECTIVES: To evaluate the cost-effectiveness and functional status effects of terazosin, an alpha(1)-adrenoceptor antagonist, compared with placebo in the treatment of men with moderate to severe, symptomatic, benign prostatic hyperplasia (BPH). METHODS: Prospective, randomized, double-blind, placebo-controlled multicenter trial of 2084 patients was conducted at 15 academic regional centers and 141 community-based satellite centers. Information about the use of health care resources and non-disease-specific functional status measures was collected by a standardized telephone interview of patients at baseline and every month thereafter for 12 months. Other information, such as American Urologic Association (AUA) disease-specific functional status scores, was obtained from the patient study records. Patients had a mean age of 65.7 years (range, 46 to 94), with a clinical diagnosis of BPH. At baseline men had at least moderate BPH symptoms by AUA Symptom score (13 or more) and Bother Score (8 or more). On entry, patients at regional sites had peak urinary flow rates 15 mL/s or less and total voided urine volumes 150 mL or greater. A total of 1053 patients were randomized to terazosin and 1031 to placebo treatment. Primary outcome measures included payments for all direct medical resource consumption (inpatient care, emergency department care, outpatient care, and medications); changes in three AUA disease-specific functional status indicators, (Symptom, Bother, and Quality of Life scores), and non-disease-specific functional status measures (days of work loss, days of customary activity loss, and days of bed rest). RESULTS: Total payments for health care resource (including study drug medication), adjusted to reflect 1000 patients per treatment group, were $3,781,803 and $3,568,263 in the placebo and terazosin groups, respectively. All three AUA disease-specific functional status scores improved significantly more in the terazosin group than in the placebo group. We found no difference between terazosin and placebo in all three nonspecific functional status measures. CONCLUSIONS: Compared with placebo, terazosin therapy for moderate to severe symptomatic BPH results in approximately equivalent payments for direct medical care, better disease-specific functional status improvement, and comparable change in non-disease-specific functional status measures.