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Biomedical subjects

Claus G Roehrborn

Publications and source records attributed to Claus G Roehrborn.

At least 19 recordsLinked to original sources
PubMed2004

Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

CONTEXT: Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. OBJECTIVE: To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. DESIGN, SETTING, AND PATIENTS: Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. MAIN OUTCOME MEASURE: Disease progression after salvage radiotherapy, defined as a serum PSA value > or =0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. RESULTS: Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P =.001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P =.02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level < or =2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less. CONCLUSIONS: Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.

Adult↗
PubMed2004

Survivin expression is associated with features of biologically aggressive prostate carcinoma.

BACKGROUND: Survivin counteracts cell death and controls mitotic progression. The objectives of the current study were to compare the expression patterns of survivin in normal prostate, primary prostate carcinoma, and lymph node tissues involved with prostate carcinoma and to determine whether the expression of survivin is associated with prostate carcinoma characteristics and progression. METHODS: Immunohistochemical staining for survivin and for transforming growth factor beta1 (TGF-beta1) and its receptors (types I and II; TGF-betaR1 and TGF-betaR2, respectively) was carried out on archival specimens from 114 consecutive patients who underwent radical prostatectomy (median follow-up, 64.8 months). Punch biopsies of the index carcinoma and normal tissue from each specimen were sectioned onto a single slide and stained. The authors also evaluated the expression of survivin in normal and malignant lymph node tissue from eight patients. RESULTS: Survivin was expressed in 41 of 114 normal prostate specimens (36%) from prostates that contained carcinoma, in 81 of 114 primary prostate carcinoma specimens (71%), in 3 of 8 normal lymphoid specimens (38%), and in 7 of 8 prostate carcinoma lymphoid specimens (88%). Survivin expression was associated with higher final Gleason sum (P = 0.001), loss of TGF-betaR1 and TGF-betaR2 expression (P = 0.041 and P = 0.008, respectively), and an increased risk of biochemical progression on univariate analysis (P = 0.0441). Among patients who had disease progression, survivin was expressed more commonly in those who had tumors with features of aggressive behavior. CONCLUSIONS: The expression of survivin gradually increased from normal prostate tissue, to low-grade primary carcinoma, to high-grade primary carcinoma and was highest in lymph node metastases. Survivin expression was associated further with alteration of the TGF-beta pathway and with overall and aggressive biochemical progression after radical prostatectomy.

Adult↗
PubMed2004

Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia.

PURPOSE: We provide a comprehensive overview of the role of alpha1-adrenergic receptors (alpha1ARs) as critical mediators of lower urinary tract symptoms (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH), and we review the pharmacological antagonists of alpha1ARs. MATERIALS AND METHODS: A review was performed of pertinent studies in the literature relating to the pathophysiology of LUTS and BPH, focusing on the role of alpha1ARs, and of clinical trial and practice data evaluating the different agents that inhibit these receptors. RESULTS: Further characterization of the alpha1AR gene family indicates that 3 receptor subtypes exist in humans. Their different distribution between urinary tract and cardiovascular tissues has provided a strategy for the development of improved therapeutic agents. Since excessive activity of the alpha1aAR and alpha1dAR subtypes appears to be a common feature in symptomatic BPH and alpha1aARs are enriched in prostatic tissue, drugs that demonstrate high alpha1aAR selectivity have attracted attention. Tamsulosin, which has high affinity for alpha1aAR and alpha1dAR subtypes but not for alpha1bAR, shows efficacy similar to the nonsubtype selective agents terazosin and doxazosin. It is associated with fewer cardiovascular side effects, although it has some ejaculatory side effects. The nonsubtype selective agent alfuzosin also demonstrates efficacy and offers an enhanced side effect profile, particularly minimizing hypotension. Other agents with super selective specificity for the alpha1aAR subtype are under investigation. CONCLUSIONS: Further advances in the treatment of LUTS associated with BPH may depend not only on receptor subtype selectivity, but also on other pharmacokinetic and pharmacodynamic factors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2004

Sustained decrease in incidence of acute urinary retention and surgery with finasteride for 6 years in men with benign prostatic hyperplasia.

PURPOSE: We determined the effect of long-term treatment with finasteride on the incidence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH) related surgery in men with BPH. MATERIALS AND METHODS: The Proscar (Merck and Co., Inc., Whitehouse Station, New Jersey) Long-Term Efficacy and Safety Study (PLESS) was comprised of 3040 men with enlarged prostates, moderate to severe symptomatic BPH and no clinical evidence of prostate cancer. Patients were randomized to placebo or 5 mg finasteride daily for 4 years. Of the 3016 randomized patients with available efficacy data 62% completed the original 4-year study (1006 on finasteride and 891 on placebo) and 89% of these (908 from the original finasteride arm and 785 from the placebo arm) continued in a 2-year open extension on finasteride. Followup was attempted in discontinued patients. Complete 6-year outcomes data, including 6-year followup in 770 men who had discontinued treatment during years 1 to 6, were available for 2463 (82%) of the 3016 originally randomized patients. RESULTS: For patients on continuous finasteride treatment the decrease in incidence of AUR and/or BPH related surgery in the 4-year base study was sustained during the open extension. In patients who were switched from placebo to finasteride in the extension, the incidence of AUR and/or BPH related surgery was similar to that in the continuous finasteride arm. CONCLUSIONS: The 6-year data from PLESS confirmed and further extended the findings from the original 4-year trial, demonstrating that finasteride treatment led to a sustained decrease in the incidence of AUR and/or BPH related surgery in men with BPH and enlarged prostates.

Acute Disease↗
PubMed2004

Lymphovascular invasion is a pathological feature of biologically aggressive disease in patients treated with radical prostatectomy.

UNLABELLED: We examined whether invasion of lymphatic and/or vascular vessels (LVI), or perineural spaces (PNI) is associated with prostate cancer features and outcome. MATERIALS AND METHODS: A total of 630 consecutive men underwent radical retropubic prostatectomy for clinically localized disease. LVI and PNI examination was part of the routine specimen evaluation. RESULTS: Foci of LVI were identified in 32 patients (5%) and 381 (60.5%) had PNI. LVI and PNI were associated with clinical stage T2 disease, higher biopsy and final Gleason sum, extraprostatic extension, seminal vesicle involvement, positive surgical margins and a higher percent of positive biopsy cores (p <0.001). LVI was associated with metastases to regional lymph nodes and higher preoperative serum prostate specific antigen (p <0.001 and 0.004, respectively). PNI and LVI were associated with an increased risk of rapid biochemical progression after radical prostatectomy on univariate (p <0.001 and 0.001, respectively) but not on multivariate analysis. LVI was associated with shorter prostate specific antigen doubling time after biochemical progression (p = 0.012) and higher probabilities of failed local salvage radiation therapy (p = 0.0169), distant metastases (p <0.001) and death (p <0.001). CONCLUSIONS: Only LVI is associated with metastases to regional and distant sites, and most importantly with overall survival. LVI and PNI are associated with established markers of biologically aggressive disease and rapid biochemical progression in patients who underwent radical prostatectomy. Our findings support the routine evaluation of LVI status in radical prostatectomy specimens and its inclusion in predictive models for clinical outcomes, since it appears to be a pathological marker of the lethal phenotype of prostate cancer.

Adult↗
PubMed2003

The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

5-alpha Reductase Inhibitors↗
PubMed2003

Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses.

OBJECTIVES: To determine the clinical utility of urine-based bladder tumor markers (UBBTMs) and cytology in the treatment of patients with transitional cell carcinoma on the basis of their statistical performance. METHODS: A comprehensive literature review was performed using Medline (1966 to current) and other search engines. Data regarding the statistical performance of UBBTMs were double extracted and rectified. Studies addressing comparable patient populations were combined and hierarchical Bayesian meta-analyses performed to calculate the sensitivity and specificity of commonly used UBBTMs, as well as urinary cytology. Patient populations were stratified by tumor stage and grade when data were presented in an extractable fashion. RESULTS: The literature review yielded 54 publications, 338 distinct patient groups (controls, screening population, patients with cancer, strata based on grade and stage) and more than 10,000 patients. The number of groups varied from 1 to 18, and the number of patients ranged from less than 100 to more than 1500 for the various markers. All UBBTMs have better sensitivity compared with cytology, especially for low-grade/stage disease, but do not match cytology regarding specificity. In patients with grade 1 and 2 tumors, several UBBTMs are significantly superior statistically in terms of sensitivity compared with cytology. The sensitivity for transitional cell carcinoma in situ (Tis) is surprisingly poor for all UBBTMs. CONCLUSIONS: UBBTMs can be used for follow-up of low-grade/stage tumors but should not replace cystoscopy. All UBBTMs have better sensitivity than cytology and could potentially replace routine cytology during patient follow-up.

Bayes Theorem↗
PubMed2003

Salvage radiotherapy for biochemical failure of radical prostatectomy: a single-institution experience.

OBJECTIVES: To review the efficacy of salvage radiotherapy (RT), to treat elevated prostate-specific antigen (PSA) levels for presumed local recurrence of prostatic adenocarcinoma after retropubic prostatectomy, and identify the factors that may predict for successful treatment. METHODS: Fifty-one patients with hormonally naive pT2-3N0-1M0 prostate cancer were treated with RT for locally persistent or recurrent disease. The patients received a median dose of 65.7 Gy (range 61.2 to 72.3) to the prostate bed. Successfully treated patients had undetectable PSA levels; the endpoint of the study was biochemical failure. RESULTS: The median follow-up was 3.8 years; 42 of 51 patients had at least 2 years of follow-up. Twenty-three patients (45%) were biochemically free of disease. The estimated biochemically free of disease rate at 3 and 5 years was 56% and 16%, respectively. Whether the patients were treated for persistently elevated PSA levels or for rising PSA levels from undetectable levels after retropubic prostatectomy, their PSA values were equally likely to drop to undetectable levels (65%). Univariate analysis demonstrated two factors that significantly predicted for successful salvage treatment: the absence of seminal vesicle invasion and the absence of lymphovascular invasion. A pretreatment PSA level less than 0.425 ng/mL trended toward statistical significance (P = 0.059). Only seminal vesicle invasion maintained significance on multivariate analysis. The RT was well tolerated, and the gastrointestinal and genitourinary toxicity was largely Radiation Therapy Oncology Group grade 1. CONCLUSIONS: Salvage RT is moderately effective in treating patients with locally persistent or recurrent prostate adenocarcinoma. Seminal vesicle invasion and lymphovascular invasion predicted for unsuccessful treatment.

Adenocarcinoma↗
PubMed2003

Distinguishing neurogenic from non-neurogenic detrusor overactivity: a urodynamic assessment of lower urinary tract symptoms in patients with and without Parkinson's disease.

OBJECTIVES: To examine the urodynamic (UDS) attributes of detrusor overactivity (DO) in patients with Parkinson's disease in comparison to DO in men without neurologic disease, in whom DO is presumably outlet obstruction induced. METHODS: The UDS database was reviewed for three groups of patients: group 1, men with lower urinary tract symptoms (LUTS) and no known neurologic condition with DO (n = 22); group 2, men with Parkinson's disease and LUTS (n = 39); and group 3, women with Parkinson's disease and LUTS (n = 18). Statistical analysis was used to compare the UDS parameters and diagnoses among the groups and to test for associations between Parkinson's disease duration, Hoehn and Yahr score, and UDS findings. RESULTS: Patients with Parkinson's disease had a significantly lower median volume at first detrusor contraction than those with non-neurogenic DO. The percentage of group 1 patients with urge incontinence was significantly lower than that found in the other two groups (9.1% versus 53.8% and 55.6%, P <0.001 and 0.002, respectively). No statistically significant correlation between the duration or severity of Parkinson's disease and UDS parameters was found. CONCLUSIONS: Men with non-neurogenic LUTS are less likely to have urge incontinence on UDS than either men or women with Parkinson's disease. DO owing to Parkinson's disease occurs earlier during filling compared with non-neurogenic DO, especially in women. The duration and severity of Parkinson's disease are not predictive of the nature or severity of UDS abnormalities.

Aged↗
PubMed2003

First dose efficacy of alfuzosin once daily in men with symptomatic benign prostatic hyperplasia.

OBJECTIVES: To evaluate the onset of action of alfuzosin once daily (OD) as determined by uroflowmetry early after initial dosing. Alfuzosin OD is an extended-release formulation of a uroselective, alpha1-adrenoreceptor-blocking agent (alpha-blocker) used in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: This was a randomized, placebo-controlled, two-way Latin square crossover study. Forty-nine patients were selected for this study on the basis of their symptomatic improvement during previous treatment with alpha-blockers and significant decreases in urinary flow rate when that treatment was withdrawn. RESULTS: Our analysis showed that significant increases in the maximal urinary flow rate (Qmax) in 34 assessable patients occurred as soon as 8 hours after the initial dose of medication and persisted for at least 4 days. The DeltaQmax for alfuzosin 10 mg OD was 3.2 mL/s and for placebo it was 1.1 mL/s. The difference of means for the assessable population was 2.1 (95% confidence interval 0.8 to 3.4, P = 0.002). The overall incidence of adverse events was low. Only dizziness, experienced by 3 patients treated with alfuzosin compared with 1 patient treated with placebo, appeared to be related to the study drug. CONCLUSIONS: Together, our findings suggest that alfuzosin OD exhibits a urodynamically measurable effect on bladder outlet obstruction due to benign prostatic hyperplasia in men with lower urinary tract symptoms within hours of the first administration.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2003

Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia.

OBJECTIVES: To examine the effect of finasteride on serum testosterone in men with benign prostatic hyperplasia (BPH). METHODS: The Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year trial comparing the safety and efficacy of finasteride 5 mg with placebo in 3040 men with moderate to severe symptomatic BPH and enlarged prostates. PLESS included the prospective measurement of annual serum testosterone in a randomly selected subset of patients comprising approximately 10% of the randomized population (n = 301). RESULTS: Finasteride treatment led to a modest, but significant (P <0.001), increase relative to placebo in serum testosterone, with this increase greatest in patients who had low baseline testosterone levels. The larger testosterone increases seen in finasteride-treated patients in the lower baseline testosterone tertiles were associated with significant mean reductions relative to placebo at year 4 in body mass index (BMI), ranging from 0.6 to 0.8 kg/m2. No statistically significant between-group difference was found in BMI in the upper testosterone tertile. The sexual adverse experience profiles for finasteride and placebo were similar across the baseline testosterone cohorts examined. CONCLUSIONS: Finasteride treatment led to a generally modest increase relative to placebo in serum testosterone, with the greatest increases occurring in men with low baseline testosterone levels. The physiologic significance of these changes in men with low baseline testosterone levels is unclear, but the associated reduction in BMI is intriguing and may be related, because BMI is known to be negatively correlated with serum testosterone levels in men.

5-alpha Reductase Inhibitors↗
PubMed2003

Factors influencing the outcomes of penile prosthesis surgery at a teaching institution.

OBJECTIVES: To evaluate the long-term outcomes of penile prosthesis surgery at a teaching institution. METHODS: Patients who had penile prosthesis surgery from 1988 to 1999 at a private teaching hospital and the Dallas Veterans Affairs Medical Center were identified and charts abstracted for age at first prosthesis, ethnicity, etiology of impotence, comorbid medical disease, previous treatments, surgeon, type of prosthesis, perioperative complications, social history, and outcome. Patient outcomes were determined either from recent clinical documentation within the prior year or by telephone survey of patients. Frequent implanters were defined as those surgeons who performed more than 10 procedures during the study period. Kaplan-Meier curves were used to evaluate survival for patients and prostheses; statistical significance was assessed by the log-rank test. RESULTS: A total of 152 patients were identified, 81 patients at the Veterans Affairs Medical Center and 71 patients at the private hospital. A total of 180 procedures were performed by 15 attending surgeons, 4 of whom performed most (n = 132) of these procedures. No statistically significant difference was noted in patient age between the two hospitals. No statistically significant differences were found in survival of the penile prostheses on the basis of a history of smoking, diabetes, hypertension, or coronary artery disease. First prostheses had statistically significant better survival compared with secondary prostheses (5-year rate 71% versus 42%; 10-year rate 60% versus 35%, P = 0.0002). The overall infection rate at final follow-up was 9.9% and 18.8% for primary and secondary prostheses, respectively (P = 0.03). The 5-year survival outcomes with first prostheses for frequent implanters were superior to those of infrequent implanters (70% versus 63%, P = 0.034). Malleable prostheses had fewer complications than three-piece inflatable prostheses (10-year survival rate 87% versus 50%, P = 0.0081). CONCLUSIONS: Superior penile prosthesis outcomes were achieved with first penile prostheses when implanted by higher volume implanters. Meticulous technique and experience are important in all penile prosthesis surgery; however, outcome analysis emphasizes that the differences in outcomes are most apparent with first prostheses, which represent the best opportunity for the patient to achieve good results.

Adult↗
PubMed2003

Heterogeneity of 5 alpha-reductase gene expression in benign prostatic hyperplasia.

PURPOSE: The search for molecular markers of benign prostatic hyperplasia in general is based on an analysis of a limited number of biopsy samples. Little is known about the homogeneity of the expression of key genes in different zones of the prostate. We studied the intraprostatic (that is within the same gland) and inter-prostatic (that is between glands) variability of 5 alpha-reductase 2 (5aR2) gene expression. MATERIALS AND METHODS: Ten tissue samples removed by open prostatectomy were the source of tissue specimens. Two frozen sections were generated from each of several random biopsies taken from each adenoma immediately after enucleation, 1 of which was used for 5aR2 gene expression analysis and 1 for morphometric analysis. Results among biopsies were compared using the 5 alpha-reductase index (ratio of 5 alpha-reductase expression to an internal standard measured as electrophoretic band intensity). Morphometric composition was determined for smooth muscle, collagen, epithelium and glandular lumens. Statistical comparisons were performed with ANOVA by pairwise multiple comparison (Dunn) and Spearman's rank correlation procedure. RESULTS: For the 71 biopsies analyzed mean 5 alpha-reductase index was 0.23 +/- 0.16 and overall tissue distribution was smooth muscle 34%, collagen 35%, epithelium 14% and glandular lumens 17%. Inter-prostate and intraprostate variability in 5 alpha-reductase index was statistically significant (p = 0.004) as was the variability in stromal-to-epithelial ratio (p = 0.012). The 5 alpha-reductase index showed strong correlation with stroma (%) and negative correlation with epithelium (%). CONCLUSIONS: Benign prostatic hyperplasia is heterogeneous in terms of tissue morphometry and expression of single important genes. This finding limits the use of single biopsy based markers to predict biological behavior, and has significant impact on the ability of distinguishing longitudinal changes in tissue composition from sampling artifacts.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

Nadir prostate-specific antigen as a predictor of progression to androgen-independent prostate cancer.

OBJECTIVES: To determine the value of the before and after treatment level of prostate-specific antigen (PSA) to predict the time to androgen-independent progression (AIP) in patients with advanced prostate cancer who received androgen-deprivation therapy (ADT) at the time of recurrence or progression. METHODS: The records of 153 patients with advanced or metastatic prostate cancer who were treated with ADT were retrospectively reviewed. Fifty-six percent of the patients were initially treated with ADT. In the remainder, ADT was started at progression and/or failure. AIP was defined as two consecutive elevations of serum PSA above the nadir value by any threshold. Kaplan-Meier and multiple logistic regression analyses were used to determine the potential predictors of AIP. RESULTS: The median duration of the PSA response was 24 months. The most important predictors of the time to AIP were the initial Gleason grade and the nadir PSA level after the initiation of ADT. The odds ratio of having a response greater than 24 months was 15-times higher in patients achieving an undetectable serum PSA level versus those who did not. For each point increase in the Gleason sum, patients had a five times higher chance of progressing to AIP in 24 months or less. CONCLUSIONS: The ability to achieve an undetectable nadir PSA level and the initial Gleason grade are significant predictors of the time to AIP in men treated with ADT for metastatic and advanced prostate cancer.

Aged↗
PubMed2002

Are all alpha-blockers created equal? An update.

alpha-Receptor blockers, used to treat lower urinary tract symptoms, exert effects on areas of the body other than the prostate where alpha-receptors are located, including the blood vessels and the central nervous system. alpha-Receptors in the central and peripheral nervous system may be involved in bladder activation. alpha(1a)-Receptors are the appropriate target in men with obstructive symptoms, although alpha(1d)-receptors may also be important in patients with irritative symptoms. There is conflicting evidence about the selectivity of alpha-blockers. Clinical trials of these agents do not necessarily reflect results observed in animal and laboratory studies on uroselectivity. The few published comparator studies of alpha-blockers indicate similar efficacies, although side-effect profiles differ somewhat. Randomized, controlled studies of different alpha-blockers with sufficient power to detect differences in side effects between agents are needed.

Adrenergic alpha-Antagonists↗
PubMed2002

Cost comparison for laparoscopic nephrectomy and open nephrectomy: analysis of individual parameters.

OBJECTIVES: To identify the cost components of laparoscopic nephrectomy (LN) that could be targeted to reduce the cost of the procedure. LN is typically more costly than open nephrectomy (ON) because of longer operative times and the use of disposable equipment. METHODS: We compared the overall cost and individual cost centers for uncomplicated LN (n = 11) and ON (n = 8) at a large metropolitan county hospital. A model was created using the DATA program (TreeAge software, version 3.5) to compare the costs of treatment with either ON or LN. We conducted a series of one-way sensitivity analyses to evaluate the effect of varying individual probabilities and costs. Two-way sensitivity analyses were performed to evaluate the costs of ON and LN while varying the hospital length of stay, operative time, and cost of laparoscopic equipment. RESULTS: LN was less costly overall than ON by $1211 (P = 0.037), despite significant differences favoring ON in overall operating room costs and operating room supply costs. The cost superiority of LN was a consequence of statistically significant differences in the cost of hospitalization, including room and board, that favored the laparoscopic group. One-way sensitivity analyses showed that LN was less costly if (a) the operative time of LN was less than 281 minutes; (b) the length of hospitalization after LN was less than 5.8 days; (c) the operating room costs for LN were less than $3439; (d) the laparoscopic equipment costs were less than $2129; (e) the ON time exceeded 78 minutes; (f) the length of hospitalization for ON was more than 3.6 days; or (g) the operating room costs for ON were greater than $1333. CONCLUSIONS: The sensitivity analyses enable individual surgeons and institutions to determine the cost impact of ON and LN, given their unique clinical scenarios. At our institution, key cost centers in determining cost effectiveness include length of operating time, hospitalization, and cost of laparoscopic instrumentation for ON and LN. LN is cost effective compared with ON if short operating times and brief length of stays are achieved.

Costs and Cost Analysis↗
PubMed2002

Reporting of acute urinary retention in BPH treatment trials: importance of patient follow-up after discontinuation and case definitions.

OBJECTIVES: A growing number of reports of retrospective analyses of adverse events occurring during studies with alpha-blockers in men with benign prostatic hyperplasia (BPH) have compared acute urinary retention (AUR) event rates with placebo-controlled finasteride trials. Because of differences in study designs, the present analysis was undertaken to compare data on the rates of AUR across different BPH trials accurately. METHODS: We report the incidence of spontaneous AUR for placebo, finasteride, and alpha-blockers based on published data in randomized clinical trials in men with BPH. RESULTS: On the basis of the data from all published randomized finasteride and alpha-blocker studies reporting AUR, the overall incidence rate for spontaneous AUR during active treatment with placebo, alpha-blockers, and finasteride ranged from 0.9 to 5.2, 0 to 1.2, and 0.3 to 1.2, respectively. The only study to provide data on AUR occurring during post-treatment follow-up was the Proscar Long-Term Efficacy and Safety Study (PLESS), in which approximately 25% of events occurred in patients after they had discontinued the study. Several of the alpha-blocker studies had significantly shorter durations, relatively small patient populations with smaller prostate volumes, lower numbers of events reported, and higher discontinuation rates with no follow-up, all of which could tremendously affect the reporting of AUR. Additionally, only PLESS reported on both spontaneous and precipitated AUR. CONCLUSIONS: Simply comparing the reported rates of AUR from published studies without taking into consideration spontaneous versus precipitated AUR, discontinuation rates, total patient follow-up, and prostate volume does not adequately allow for comparison of the true event rate across different clinical trials.

Acute Disease↗