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T J Wilt

Publications and source records attributed to T J Wilt.

At least 19 recordsLinked to original sources
PubMed2006

Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer.

BACKGROUND: Hormone therapy for early prostate cancer has demonstrated an improvement in clinical and pathological variables, but not always an improvement in overall survival. We performed a systematic review of both adjuvant and neo-adjuvant hormone therapy combined with surgery or radiotherapy in localised or locally advanced prostate cancer. OBJECTIVES: The objective of this review was to undertake a systematic review and, if possible, a meta-analysis of neo-adjuvant and adjuvant hormone therapy in localised or locally advanced prostate cancer. SEARCH STRATEGY: We searched MEDLINE (1966-2006), EMBASE, The Cochrane Library, Science Citation Index, LILACS, and SIGLE for relevant randomised trials. Handsearching of appropriate publications was also undertaken. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of patients with localised or locally advanced prostate cancer, that is, stages T1-T4, any N, M0, comparing neo-adjuvant or adjuvant hormonal deprivation in combination with primary therapy (radical radiotherapy or radical prostatectomy) versus primary therapy alone were included in this review. DATA COLLECTION AND ANALYSIS: Data were extracted from eligible studies and assessed for quality, and included information on study design, participants, interventions, and outcomes. Comparable data were pooled together for meta-analysis with intention-to treat principle. MAIN RESULTS: Men with prostate cancer have different clinical outcomes based on their risk (T1-T2, T3-T4, PSA levels and Gleason score). However, the majority of studies included in this review did not report results by risk groups; therefore, it was not possible to perform sub-group analysis. Neo-adjuvant hormonal therapy prior to prostatectomy did not improve overall survival (OR 1.11, 95% CI 0.67 to 1.85, P = 0.69). However, there was a significant reduction in the positive surgical margin rate (OR 0.34, 95% CI 0.27 to 0.42, P < 0.00001) and a significant improvement in other pathological variables such as lymph node involvement, pathological staging and organ confined rates. There was a borderline significant reduction of disease recurrence rates (OR 0.74, 95% CI 0.55 to 1.0, P = 0.05), in favour of treatment. The use of longer duration of neo-adjuvant hormones, that is either 6 or 8 months prior to prostatectomy, was associated with a significant reduction in positive surgical margins (OR 0.56, 95% CI 0.39 to 0.80, P = 0.002). In one study, neo-adjuvant hormones prior to radiotherapy significantly improved overall survival for Gleason 2 to 6 patients; although, in two studies, there was no improvement in disease-specific survival (OR 0.99, 95% CI 0.75 to 1.32, P = 0.97). However, there was a significant improvement in both clinical disease-free survival (OR 1.86, 95% CI 1.93 to 2.40, P < 0.00001) and biochemical disease-free survival (OR 1.93, 95% CI 1.45 to 2.56, P < 0.00001). Adjuvant androgen deprivation following prostatectomy did not significantly improve overall survival at 5 years (OR 1.50, 95% CI 0.79 to 2.85, P = 0.2); although one study reported a significant disease-specific survival advantage with adjuvant therapy (P = 0.001). In addition, there was a significant improvement in disease-free survival at both 5 years (OR 3.73, 95%CI 2.30 to 6.03, P < 0.00001) and 10 years (OR 2.06, 95% CI 1.34 to 3.15, P = 0.0009). Adjuvant therapy following radiotherapy resulted in a significant overall survival gain apparent at 5 (OR 1.46, 95% CI 1.17 to 1.83, P = 0.0009) and 10 years (OR 1.44, 95% CI 1.13 to 1.84, P = 0.003); although there was significant heterogeneity (P = 0.09 and P = 0.07, respectively). There was also a significant improvement in disease-specific survival (OR 2.10, 95% CI 1.53 to 2.88, P = 0.00001) and disease-free survival (OR 2.53, 95% CI 2.05 to 3.12, P < 0.00001) at 5 years. AUTHORS' CONCLUSIONS: Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer. Significant local control may be achieved when given prior to prostatectomy or radiotherapy, which may improve patient's quality of life. When given adjuvant to these primary therapies, hormone therapy, not only provides a method for local control, but there is also evidence for a significant survival advantage. However, hormone therapy is associated with significant side effects, such as hot flushes and gynaecomastia, as well as cost implications. The decision to use hormone therapy should, therefore, be taken at a local level, between the patient, clinician and policy maker, taking into account the clinical benefits, toxicity and cost. More research is needed to guide the choice, the duration, and the schedule of hormonal deprivation therapy, and the impact of long-term hormone therapy with regard to toxicity and the patient's quality of life.

Androgen Antagonists↗
PubMed2004

Laser prostatectomy for benign prostatic obstruction.

BACKGROUND: Symptomatic benign prostatic obstruction is a common problem for older men. The gold standard treatment, transurethral resection of the prostate (TURP), significantly improves urinary symptoms and urinary flow. However, TURP has up to a 20% morbidity. Currently, there are a number of minimally invasive procedures that may be safe, effective alternatives to TURP. One promising surgical technique is laser prostatectomy. OBJECTIVES: To assess the therapeutic efficacy and safety of laser prostatectomy techniques for treating men with symptomatic benign prostatic obstruction. SEARCH STRATEGY: Randomized controlled trials were identified from the Cochrane Collaboration Library, MEDLINE, EMBASE, bibliographies of retrieved articles and reviews, and contacting expert relevant trialists and laser manufacturers. SELECTION CRITERIA: All randomized controlled trials evaluating laser prostatectomy treatment for men with symptomatic BPH. Trials were eligible if they (1) were randomized comparisons of a laser technique with TURP, (2) included at least 10 men with BPO in each treatment arm, (3) provided at least 6-months follow-up, and (4) included clinical outcomes such as urologic symptom scales or urodynamic measurements. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodologic quality was performed independently by two reviewers. Information on study design, subject and treatment characteristics, adverse events, urinary symptoms, and urinary flow were extracted using a standard form. MAIN RESULTS: 20 studies involving 1898 subjects were evaluated, including studies 4 with multiple comparisons. We found 8 comparisons of TURP with contact lasers, 8 with non-contact lasers, 4 with hybrid techniques, and one with interstitial laser coagulation (ILC). Two studies compared transurethral electrovaporization (TUVP) with contact lasers, one study compared interstitial laser coagulation with transurethral microwave thermotherapy (TUMT), and one study compared holmium contact lasers (HoLRP) with open prostatectomy. Among the studies comparing laser prostatectomy with TURP, follow-up duration ranged from 6 to 36 months. Mean age (67.2 yrs), mean baseline symptom score (20.2), and mean baseline peak urinary flow (9.2 ml/s) did not differ by treatment group. The pooled percentage improvements for mean urinary symptoms ranged from 59% to 68% with lasers and 63% to 77% with TURP. The improvements for mean peak urinary flow ranged from 56% to 119% with lasers and 96% to 127% with TURP. Overall, laser subjects were less likely to receive transfusions or develop strictures and their hospitalizations were shorter. Non-contact laser subjects were more likely to have dysuria, urinary tract infection, and retention. Re-operation occurred more often following laser procedures. REVIEWER'S CONCLUSIONS: Laser techniques are a useful alternative to TURP for treating BPO. Small sample sizes and differences in study design limit any definitive conclusions regarding the preferred type of laser technique. Data were insufficient to compare laser techniques with other minimally invasive procedures.

Aged↗
PubMed2004

A meta-analysis of randomised trials suggests a survival benefit for combined radiotherapy and radical cystectomy compared with radical radiotherapy for invasive bladder cancer: are these data relevant to modern practice?

OBJECTIVE: Treatment options for muscle-invasive bladder cancer include radical cystectomy or radical radiotherapy, and the prevailing choice varies by country. The ideal treatment would be a bladder-preserving therapy without compromising survival. The objective of this review was to compare the overall survival after radical surgery (cystectomy) with radical radiotherapy in patients with muscle-invasive cancer. MATERIALS AND METHODS: We searched the Cochrane Controlled Trials Register, Medline, EMBASE, Cancerlit, Healthstar and the Database of Abstracts of Reviews of Effectiveness. Authors of unpublished data were contacted. Randomised trials comparing surgery (alone or with preoperative radiotherapy) with radiotherapy were eligible for assessment. Three reviewers assessed trial quality based on the Cochrane Guidelines. Data were extracted from the text of the article or extrapolated from the Kaplan-Meier plot. The Peto odds ratio was determined to compare the overall survival and disease-specific survival. Analysis was performed on an intention-to-treat basis and treatment actually received. RESULTS: No randomised trials comparing surgery alone with radiotherapy alone were identified. Three randomised trials comparing preoperative radiotherapy followed by radical cystectomy (surgery) versus radical radiotherapy with salvage cystectomy (radical radiotherapy) were eligible for assessment. These trials represented a total of 439 patients, 221 randomised to surgery and 218 to radical radiotherapy. Three trials were combined for the overall survival results, and one was evaluable for the disease-specific survival analysis. The mean overall survival (intention-to-treat analysis) at 3 and 5 years were 45% and 36% for surgery, and 28% and 20% for radiotherapy, respectively. Peto odds ratio (95% confidence interval [CI]) analysis consistently favoured surgery in terms of overall survival. The results were significantly in favour of surgery at 3 years (OR = 1.91, 95% CI 1.30-2.82) and at 5 years (OR = 1.85, 95% CI 1.22 -2.82). On a treatment-received basis, the results were significantly in favour of surgery at 3 years (OR 1.84, 95% CI 1.17-2.90) and 5 years (OR 2.17, 95% CI 1.39-3.38) for overall survival, and at 3 years (OR 1.96, 95% CI 1.06-3.65) for disease-specific survival. CONCLUSIONS: The analysis of this review suggests that there is an overall survival benefit with combined preoperative radiotherapy plus radical surgery compared with radical radiotherapy plus salvage cystectomy in patients with muscle-invasive bladder cancer. However, it must be considered that only three trials were included for analysis, the patient numbers were small and that many patients did not receive the treatment they were randomised to. It must also be noted that many improvements in radiotherapy and surgery have taken place since the initiation of these trials; therefore, the data may not be readily extrapolated to modern practice. Ideally, a new trial comparing modern bladder-sparing therapy with the latest surgical approach to this disease is required.

Cystectomy↗
PubMed2004

Intravesical bacillus Calmette-Guérin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials.

OBJECTIVE: To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical mitomycin C and bacillus Calmette-Guérin (BCG) for tumour recurrence, disease progression and overall survival in patients with medium- to high-risk Ta and T1 bladder cancer. METHODS: The major medical databases were searched comprehensively up to June 2003, and relevant journals hand-searched for randomized controlled trials, in any language, that compared intravesical mitomycin C with BCG in medium- to high-risk patients with Ta or T1 bladder cancer. RESULTS: Twenty-five articles were identified but only seven were considered eligible for the analysis. This represented 1901 evaluable patients in all, 820 randomized to mitomycin C and 1081 to BCG. Six trials had sufficient data for meta-analysis and included 1527 patients, 693 in the mitomycin and 834 in the BCG arm. There was no significant difference between mitomycin C and BCG for tumour recurrence in the six trials, with a weighted mean log hazard ratio, LHR, (variance) of -0.022 (0.005). However, there was significant heterogeneity between trials (P = 0.001). A subgroup analysis of three trials that included only high-risk Ta and T1 patients indicated no heterogeneity (P = 0.25) and a LHR for recurrence of -0.371 (0.012). With mitomycin C used as the control in the meta-analysis, a negative ratio is in favour of BCG and, in this case, was highly significant (P < 0.001). The seventh trial (in abstract form only) used BCG in low doses for two arms of the trial (27 mg and 13.5 mg) compared with a standard dose of mitomycin C (30 mg), and reported a significantly lower recurrence rate with BCG (27 mg) than for mitomycin C (P = 0.001). Only two trials included sufficient data to analyse disease progression and survival, representing 681 patients (338 randomized to BCG and 343 to mitomycin C). There was no significant difference between mitomycin C and BCG for disease progression, with a LHR of 0.044 (0.04) (P = 0.16), or survival, at -0.112 (0.03) (P = 0.50). Adverse events were slightly more frequent with BCG. Local toxicity (dysuria, cystitis, frequency and haematuria) were associated with both mitomycin C (30%) and BCG (44%). Systemic toxicity, e.g. chills, fever and malaise, occurred with both agents (12% and 19%, respectively) although skin rash was more common with mitomycin C. CONCLUSION: Tumour recurrence was significantly lower with intravesical BCG than with mitomycin C only in those patients at high risk of tumour recurrence. However, there was no difference in disease progression or survival, and the decision to use either agent might be based on adverse events and cost.

Adjuvants, Immunologic↗
PubMed2003

Tamsulosin for benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate which can result in bothersome lower urinary tract symptoms. The treatment goal for men with BPH is to relieve these bothersome symptoms. OBJECTIVES: This systematic review assessed the effects of tamsulosin in the treatment of lower urinary tract symptoms (LUTS) compatible with BPH. SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were eligible if they (1) randomized men with BPH to receive tamsulosin in comparison with placebo, other BPH medications or surgical interventions and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements, and (3) had a treatment duration of 30 days or longer. Eligibility was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes were extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of tamsulosin with placebo, medical or surgical interventions was the change in urologic symptom scale scores. Secondary outcomes included changes in urinary flow measures (peak urine flow rate). The main outcome measure for adverse effects was the number of men reporting adverse effects. MAIN RESULTS: Fourteen studies involving 4,122 subjects met inclusion criteria. Study duration ranged from 4-26 weeks, and no placebo-controlled study lasted longer than 13 weeks. The mean age of subjects was 64 years. Baseline symptom scores and urine flow rates demonstrated that men had moderate LUTS. Tamsulosin improved symptoms and peak urine flow relative to placebo. The weighted mean differences (WMD) for mean change from baseline for the Boyarsky symptom score for 0.4 mg and 0.8 mg doses of tamsulosin relative to placebo were -1.1 points (95% CI = -1.49, -0.72; 12% improvement) and -1.6 points (95% CI = -2.3, -1.0; 16% improvement), respectively. The WMD for mean change from baseline in peak urine flow were 1.1 mL/sec (95% CI = 0.59, 1.51) and 1.1 mL/sec (95% CI= 0.65, 1.48) for 0.4 mg and 0.8 mg, respectively. Tamsulosin (0.2 mg-0.4 mg) was as effective as other alpha antagonists and the phytotherapeutic agent Permixon in improving symptoms and flow rates though the doses of all alpha-antagonists studied may not have been optimal. Discontinuations from treatment for any reason and discontinuations "due to adverse events" were similar in the low dose tamsulosin (0.2 mg) and placebo groups but increased to 16% in trials utilizing a 0.8 mg dose of tamsulosin. Low dose tamsulosin was generally well tolerated although not all the trials reported specific adverse events. The most frequently reported adverse events that were significantly greater than placebo included dizziness, rhinitis and abnormal ejaculation. Adverse effects increased markedly as tamsulosin dosing increased, and were reported in 75% of men receiving the 0.8 mg dose. Men receiving a 0.2 mg dose tamsulosin were less likely to discontinue treatment compared to men receiving terazosin. REVIEWER'S CONCLUSIONS: Tamsulosin provided a small to moderate improvement in urinary symptoms and flow compared to men receiving placebo in men with BPH. Effectiveness was similar to other alpha antagonists and increased only slightly with higher doses. Long term effectiveness and ability to reduce complications due to BPH progression could not be determined. Adverse effects were generally mild but their frequency, including withdrawals, increased substantially with the higher doses that are generally available for treatment.

Adrenergic alpha-Antagonists↗
PubMed2003

Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer.

BACKGROUND: Tumour recurrence following transurethral resection (TUR) for Ta and T1 bladder cancer is a major clinical problem. Intravesical administration of mitomycin C (MMC) or bacillus Calmette-Guerin (BCG) has proven prophylactic activity but both are associated with local and systemic side-effects. A systematic review was carried out to compare the efficacy of these two agents. OBJECTIVES: To undertake a systematic review and meta-analysis comparing intravesical mitomycin C and Bacillus Calmette-Guerin in terms of tumour recurrence, disease progression and overall survival in Ta and T1 bladder cancer. Treatment-related toxicities would also be evaluated. SEARCH STRATEGY: A comprehensive search of MEDLINE, EMBASE, Healthstar, Cochrane Controlled Trials Register, Cancerlit, and DARE was performed, and hand searching of relevant journals undertaken. SELECTION CRITERIA: Trials in any language were included in the meta-analysis if they were properly randomised, included medium to high risk patients with Ta or T1 bladder cancer and compared intravesical MMC versus BCG. DATA COLLECTION AND ANALYSIS: Trial eligibility, methodological quality and data extraction were assessed independently by two reviewers. Time to event analysis was evaluated using log hazard ratios, with a sensitivity analysis for subgroups according to patient's risk of recurrence. MAIN RESULTS: Twenty-five articles were identified but only seven were considered eligible. This represented 1901 evaluable patients in total, 820 randomised to MMC and 1081 to BCG. Six trials had sufficient data for meta-analysis and included 1527 patients, 693 in the mitomycin arm and 834 in the BCG arm. The weighted mean log hazard ratio (variance) for tumour recurrence for the six trials was - 0.022 (0.005). This indicated no significant difference between MMC and BCG (p = 0.76). However, the meta-analysis indicated evidence of significant heterogeneity between trials (p = 0.001). A subgroup analysis of three trials that included only high risk Ta and T1 patients indicated no heterogeneity (p = 0.25) and a log hazard ratio (variance) for recurrence of -0.371 ( 0.012). With MMC used as the control in the meta-analysis, a negative ratio is in favour of BCG and, in this case, is highly significant (p = 0.0008). The seventh trial, in abstract form only, used BCG in low doses for two arms of the trial (27 mg and 13.5mg) compared to a standard dose of mitomycin C (30mg), and reported a significantly reduced recurrent rate with BCG (27mg) compared to mitomycin C (p = 0.001). Only two trials included sufficient data to analyse disease progression and survival, representing a total of 681 patients; 338 randomised to BCG and 343 to MMC. There was no significant difference between MMC and BCG for disease progression (log hazard ratio + variance: 0.044 + 0.04, p = 0.16) or survival (-0.112 + 0.03, p = 0.50). Local toxicities (dysuria, cystitis, frequency, and haematuria) were associated with both MMC (30%) and BCG (44%). Systemic toxicities, such as chills, fever and malaise, were observed with both MMC and BCG (12% and 19%, respectively) although skin rash was more common with MMC. REVIEWER'S CONCLUSIONS: The data from the present meta-analysis indicate that tumour recurrence was significantly reduced with intravesical BCG compared to MMC only in the subgroup of patients at high risk of tumour recurrence. However, there was no difference in terms of disease progression or survival, and the decision to use either agent might be based on adverse events and cost.

Administration, Intravesical↗
PubMed2003

Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy--a systematic review of randomised trials.

Recent randomised studies have reported that single fraction radiotherapy is as effective as multifraction radiotherapy in relieving pain caused by bone metastasis. However, there are concerns about the higher re-treatment rates and the efficacy of preventing future complications, such as pathological fracture and spinal cord compression, by single fraction radiotherapy. A systematic review of randomised studies, examining the effectiveness of single fraction radiotherapy versus multiple fraction radiotherapy for metastatic bone pain relief and prevention of bone complications, was conducted to help answer this controversy. Randomised studies comparing single fraction radiotherapy with multifraction radiotherapy on metastatic bone pain were identified. The analyses were performed using intention-to-treat principle. The results were pooled using meta-analysis to estimate the effect of treatment on pain response, re-treatment rate, pathological fracture rate and spinal cord compression rate. Twelve trials involving 3621 sites were included in the meta-analysis. The overall pain-response rates for single fraction radiotherapy and multifraction radiotherapy were 60% (1080/1814) and 59% (1060/1807), respectively, giving an odds ratio (OR) of 1.03 (95% confidence interval [CI] 0.90-1.19), indicating no difference between the two radiotherapy schedules. There was also no difference in complete pain response rates for single fraction radiotherapy (34% [508/1476]) and multifraction radiotherapy (32% [475/1473]), with an OR of 1.10 (950% CI 0.94-1.30). Patients treated by single fraction radiotherapy had a higher re-treatment rate, with 21.5% (267/1240) requiring re-treatment compared with 7.4% (91/1236) of patients in the multifraction radiotherapy arm (OR 3.44 [95% CI 2.67-4.43]). The pathological fracture rate was also higher in single fraction radiotherapy arm patients. Three per cent (37/1240) of patients treated by single fraction radiotherapy developed pathological fracture compared with 1.6% (20/1236) for those treated by multifraction radiotherapy (OR 1.82 [95% CI 1.06-3.11]). The spinal cord compression rates were similar for both arms (OR 1.41 [95% CI 0.72-2.75]). Single fraction radiotherapy was as effective as multifraction radiotherapy in relieving metastatic bone pain. However, the re-treatment rate and pathological fracture rate were higher after single fraction radiotherapy. Studies with quality of life and health economic end points are warranted to find out the optimal treatment option.

Bone Neoplasms↗
PubMed2003

Trazodone for erectile dysfunction: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of trazodone in the treatment of erectile dysfunction (ED) in a meta-analysis. METHODS: The data sources used were Medline and the Cochrane Library databases (January 1966 to May 2002), bibliographies of retrieved articles and review articles, and conference proceedings and abstracts. Trials were eligible for inclusion in the review if they included men with ED, compared trazodone with a control, were randomized, of > or = 7 days' duration and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. RESULTS: Six trials (comprising 396 men) met the inclusion criteria; they consisted of heterogeneous populations, were small, brief and in some cases methodologically weak. Three of the six trials showed an apparently clinically meaningful benefit of trazodone for ED compared with placebo, the differences being statistically significant in two. In pooled results, trazodone monotherapy appeared more likely than placebo to lead to a 'positive treatment response', although this difference was not statistically significant (37% vs 20%; relative benefit increase, 1.6; 95% confidence interval, CI, 0.8-3.3). Subgroup analyses suggested that men with psychogenic ED might be more likely to benefit from trazodone than those with mixed or physiological ED. The efficacy of trazodone also appeared greater at higher doses (150-200 vs 50 mg/day). Men randomized to trazodone were not significantly more likely than those receiving placebo to withdraw for any reason or for an adverse event, or to have specific adverse events, but wide CIs could not exclude a greater risk of these adverse outcomes with trazodone. Specific adverse events with trazodone included dry mouth (19%), sedation (16%), dizziness (16%) and fatigue (15%). CONCLUSION: Trazodone may be helpful in men with ED, possibly more so at higher doses, and in men with psychogenic ED. Future high-quality trials should compare trazodone with placebo and other therapies in men with depression and psychogenic ED.

Adult↗
PubMed2002

Terazosin for benign prostatic hyperplasia.

BACKGROUND: Lower urinary tract symptoms associated with benign prostatic obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve these bothersome symptoms, treatment options include alpha-antagonists, also know as alpha-blockers. OBJECTIVES: We conducted a systematic review to evaluate the effectiveness and adverse effects of the alpha-blocker, terazosin, for treatment of urinary symptoms associated with BPO. SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Studies were included if they (1) were randomized trials of at least 1 month duration, and (2) included men with symptomatic BPO and compared terazosin with placebo or active controls. DATA COLLECTION AND ANALYSIS: Study, patient characteristics and outcomes data were extracted in duplicate onto standardized forms utilizing a prospectively developed protocol. The main outcome measure for comparing the effectiveness of terazosin with placebo or other BPO medications was change in urological symptoms as measured by validated symptom scores. Secondary outcomes included urodynamic measures. The main outcome measure for adverse effects was the number of men reporting side effects. We also evaluated the number of men withdrawing from treatment and the number withdrawing due to adverse effects. MAIN RESULTS: 17 studies involving 5,151 subjects met inclusion criteria (placebo-controlled (10); alpha-blockers (7); finasteride alone or in combination with terazosin as well as placebo (1); microwave therapy (TUMT) (1). Study duration ranged from 4-52 weeks. Mean age was 65 years and 82% of men were white. Baseline urologic symptom scale scores and flow rates demonstrated that men had moderate BPO. Efficacy outcomes were rarely reported in a fashion that allowed for data pooling but indicated that terazosin improved symptom scores and flow rates more than placebo or finasteride and similarly to other alpha antagonists. The pooled mean percentage improvements for the Boyarsky symptom score was 37% for terazosin versus 15% for placebo (n=4 studies). The mean percentage improvement for the American Urological Association symptom score (AUA) was 38% compared to 17% and 20% for placebo and finasteride, respectively (n = 2 studies). The pooled mean improvement in the International Prostate Symptom Score (IPSS) (40%) was similar to tamsulosin (43%). Peak urine flow rates improved greater with terazosin (22%), than placebo (11%) and finasteride (15%) but did not differ significantly from the other alpha-blockers. The percentage of men discontinuing terazosin was comparable to men receiving placebo and finasteride but was greater then with other alpha-antagonists. Adverse effects were greater than placebo and included dizziness, asthenia, headache and postural hypotension. REVIEWER'S CONCLUSIONS: The available evidence suggests that terazosin improves urinary symptoms and flow measures associated with BPO. Effectiveness is superior to placebo or finasteride, similar to other alpha-blockers but less than TUMT. Adverse effects were generally mild but more frequent than other alpha-blockers and associated with between a two-four fold increase in treatment discontinuation.

Adrenergic alpha-Antagonists↗
PubMed2002

Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects.

OBJECTIVE: To systematically review and evaluate the effectiveness and adverse effects of the alpha-antagonist, terazosin, for treating urinary symptoms associated with benign prostatic obstruction (BPO). METHODS: Studies were sought and included in the review if they were randomized trials of at least 1 month duration, involved men with symptomatic BPO and compared terazosin with placebo or active controls. The study, patient characteristics and outcome data were extracted in duplicate onto standardized forms using a prospectively developed protocol. RESULTS: Seventeen studies involving 5151 men met the inclusion criteria, i.e. placebo-controlled (10), alpha-blockers (seven), finasteride alone or combined with terazosin and placebo (one), and microwave therapy (one). The study duration was 4-52 weeks; the mean age of the men was 65 years and 82% were white. Baseline urological symptom scale scores and flow rates showed that men had moderate BPO. Efficacy outcomes were rarely reported in a way that allowed for data pooling, but indicated that terazosin improved symptom scores and flow rates more than did placebo or finasteride, and similarly to other alpha-antagonists. The pooled mean percentage improvement for the Boyarsky symptom score was 37% for terazosin and 15% for placebo (four studies). The mean percentage improvement for the American Urological Association symptom score was 38%, compared with 17% and 20% for placebo and finasteride, respectively (two studies). The pooled mean improvement in the International Prostate Symptom Score of 40% was similar to that with tamsulosin (43%). Peak urinary flow rates improved more with terazosin (22%) than with placebo (11%) and finasteride (15%), but did not differ significantly from the other alpha-antagonists. The percentage of men discontinuing terazosin was comparable with those receiving placebo and finasteride, but greater than with other alpha-antagonists. Adverse effects were greater than with placebo and included dizziness, asthenia, headache and postural hypotension. CONCLUSIONS: The available evidence indicates that terazosin improves the symptoms and flow rates associated with BPO; it was more effective than placebo or finasteride and similar to other alpha-antagonists. Adverse effects were generally mild but more frequent than with other alpha-antagonists and associated with a two- to four-fold increase in treatment discontinuation.

Adrenergic alpha-Antagonists↗
PubMed2001

Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review.

OBJECTIVES: Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen for metastatic prostate cancer has been the subject of 20 randomized trials. The findings range from no expected increase in survival in 17 studies to an estimated 3.7 to 7 months' survival improvement noted in 3 studies. Most recently, a 1999 evidence report from the Agency for Healthcare Research and Quality and a 2000 overview from the Prostate Cancer Trialists Collaborative Group indicated that combined androgen blockade was associated with an approximately 3% to 5% increase in 5-year survival. We report herein a systematic review on combined androgen blockade performed by the Cochrane Collaborative Review Group on Prostate Diseases. METHODS: Controlled trials that included a randomization of immediate nonsteroidal antiandrogens with castration versus castration alone for metastatic prostate cancer and provided information on survival were reviewed. Information on overall survival, toxicity, progression-free survival, cancer-specific survival, and type of nonsteroidal antiandrogen and castration therapies was abstracted by two independent reviewers. RESULTS: Twenty trials (n = 6320 patients) were included. The pooled odds ratio (OR) for overall survival with combined androgen blockade was 1.03 (95% confidence interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95% CI 1.00 to 1.33; n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials) at 1, 2, and 5 years, respectively. Progression-free survival was improved at 1 year (OR = 1.38; 95% CI 1.15 to 1.67; n = 2278 from 7 trials). Cancer-specific survival was improved at 5 years (OR = 1.58; 95% CI 1.05 to 2.37; n = 781 from 2 trials). When analysis was limited to studies identified as being of high quality, the pooled OR for overall survival progressively increased but was not significant at any follow-up interval. CONCLUSIONS: We find that there is a 5% improvement in the percentage of men surviving at 5 years (30% vs. 25%) with combined androgen blockade with nonsteroidal antiandrogens as well as improvements in progression-free survival at 1 year. Appropriate patients with metastatic prostate cancer should be informed of the potential benefits, toxicities, and out-of-pocket expenditures.

Androgen Antagonists↗
PubMed2001

A systematic review of intravesical bacillus Calmette-Guérin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer.

OBJECTIVE: To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer. PATIENTS AND METHODS: An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer. RESULTS: The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was -0.83 (95% confidence interval -0.57 to -1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21-0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported. CONCLUSION: TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease.

Administration, Intravesical↗
PubMed2001

Transurethral incision compared with transurethral resection of the prostate for bladder outlet obstruction: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Transurethral prostatic resection is the gold standard surgical treatment in men with lower urinary tract symptoms suggestive of bladder outlet obstruction but it has also been related to some risks, such as a relatively high rate of blood transfusion, sexual function problems and so forth. Transurethral prostatic incision is a simpler and less invasive procedure than transurethral prostatic resection. However, it is underused. We systematically reviewed all published randomized controlled trials comparing the effectiveness of transurethral prostatic incision with standard transurethral prostatic resection for bladder outlet obstruction and performed a meta-analysis of the available relevant data. MATERIALS AND METHODS: Nine randomized controlled trials comparing the treatment effectiveness of transurethral prostatic resection and transurethral prostatic incision were identified, evaluated and reviewed in a meta-analysis. The quality of these studies was also appraised. RESULTS: Each treatment achieved clear improvements in subjective and objective outcomes. The improvement in symptoms was equivalent 12 months postoperatively for transurethral prostatic incision and resection. For maximum flow rate transurethral prostatic resection resulted in greater improvement than transurethral prostatic incision. However, transurethral prostatic incision had several advantages over transurethral prostatic resection, such as lower incidence of complications, fewer blood transfusions, decreased risk of retrograde ejaculation, and shorter operative time and hospital stay. Also, the treatments had an equivalent incidence of postoperative catheterization duration and reoperation rate within the first 12 months. Furthermore, patients in each group had a similar subjective view of the treatments received. CONCLUSIONS: In the first 12 months after surgery transurethral prostatic incision has effectiveness that is equivalent to transurethral prostatic resection for treating patients with suspected benign prostatic obstruction who have a relatively small prostate. However, there is little evidence on the relative long-term effectiveness of the 2 treatments 2 to 5 or 10 years after surgery. There is no clear cutoff point for prostate size that leads to good results after transurethral prostatic incision. A large-scale, multicenter randomized controlled trial is now required to evaluate comprehensively the effectiveness, impact on quality of life and overall cost of transurethral prostatic incision compared with transurethral prostatic resection.

Humans↗