Search

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.

Background: Muscle invasive bladder cancer is a serious clinical problem and is fatal for the majority of patients. Alternative treatments for this condition are radical cystectomy or radical radiotherapy. The choice of treatment varies according to the resident country. The ideal treatment would be a bladder preserving therapy with total eradication of the tumour without compromising survival., Objectives: The objective of this review was to compare the overall survival after radical surgery (cystectomy) versus radical radiotherapy in patients with muscle invasive cancer., Search Strategy: We searched the Cochrane Controlled Trials Register (July 2001), MEDLINE (July 2001), EMBASE (July 2001), CancerLIT (July 2001), Healthstar (July 2001) and the Database of Abstracts of Reviews of Effectiveness (July 2001). Attempts to contact authors of unpublished data were undertaken., Selection Criteria: Randomised trials comparing surgery versus radiotherapy were eligible for assessment., Data Collection and Analysis: 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., Main Results: Three randomised trials comparing pre-operative 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 for the disease-specific analysis [Bloom 1982]. 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) 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 (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., Reviewer's Conclusions: The analysis of this review suggests that there is an overall survival benefit with radical surgery compared to radical radiotherapy in patients with muscle-invasive bladder cancer. However, it must be considered that only three trials were included for analysis, the patients 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 both radiotherapy and surgery have taken place since the initiation of these trials.

Background: Muscle invasive bladder cancer is a serious clinical problem and is fatal for the majority of patients. Alternative treatments for this condition are radical cystectomy or radical radiotherapy. The choice of treatment varies according to the resident country. The ideal treatment would be a bladder preserving therapy with total eradication of the tumour without compromising survival., Objectives: The objective of this review was to compare the survival after radical surgery (cystectomy) versus radical radiotherapy in patients with muscle invasive cancer., Search Strategy: We searched the Cochrane Controlled Trials Register (July 2000), Medline (July 2000), EMBASE (July 2000), Cancerlit (July 2000), Healthstar (July 2000) and the Database of Abstracts of Reviews of Effectiveness (July 2000). Attempts to contact authors of unpublished data were undertaken., Selection Criteria: Randomised trials comparing surgery versus radiotherapy were eligible for assessment., Data Collection and Analysis: Three reviewers assessed trial quality based on the Cochrane Guidelines. Data was 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., Main Results: Three randomised trials comparing pre-operative 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. Peto odds ratio analysis consistently favoured surgery in terms of survival. It was significant at 3 (OR = 2.11, 95% CI 1.10,4.07) and 5 years (OR = 2.40, 95% CI 1.35, 4.29) for overall survival and at 3 years (OR = 1.96, 95% CI 1.06,3.65) for disease-specific survival for patients that actually received the protocol treatment. On an intention-to-treat analysis for disease-specific survival, the results were significantly in favour of surgery at 3 years (OR = 1.96, 95% CI 1.06,3.65) but not at 5 years., Reviewer's Conclusions: The evidence from this review suggests that there is no overall statistically significant benefit to radiotherapy or surgery ( with pre-operative radiotherapy) in muscle invasive bladder cancer in terms of survival, but the trends consistently favour surgery.

Background: Intravesical therapy with Bacillus Calmette-Guerin (BCG) aims to reduce the incidence of tumour recurrence following transurethral resection (TUR) for patients with superficial bladder cancer., Objectives: The objective of this review was to compare the incidence of tumour recurrence after the standard therapy of transurethral resection versus transurethral resection plus intravesical Bacillus Calmette-Guerin., Search Strategy: We searched the Cochrane Controlled Trials Register (March 2000), Medline (February, 2000), EMBASE (February, 2000), Cancerlit (February, 2000), Healthstar (February, 2000), Database of Abstracts of Reviews of Effectiveness (February, 2000) and the Bath Information Data Service. The Proceedings of the American Society Clinical Oncology was hand searched (1996 - 1999)., Selection Criteria: Randomised or quasi-randomised trials of transurethral resection alone versus transurethral resection plus intravesical Bacillus Calmette-Guerin. Patients with Ta and T1 bladder cancer of medium or high risk of tumour recurrence, were eligible for inclusion., Data Collection and Analysis: Four reviewers assessed trial quality and two abstracted the data independently. The Peto odds ratios and log hazard ratios were determined to compare the number of patients with disease recurrence at 12 months and the rate of recurrence, respectively., Main Results: Six randomised trials were included involving 585 eligible patients. There were significantly fewer patients with disease recurrence at 12 months in the BCG plus TUR group compared to those that received TUR alone (odds ratio 0.30, CI 0.21, 0.43). The overall log hazard ratio for recurrence (-0.83, variance 0.02) indicated a significant benefit of BCG treatment in reducing tumour recurrence. Toxicities associated with BCG consisted mainly of cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported., Reviewer's Conclusions: In patients with medium/high risk Ta or T1 bladder cancer, immunotherapy with intravesical BCG following TUR appears to provide a significant advantage over TUR alone in delaying tumour recurrence.

Biliary excretion of platinum was measured in a patient receiving an intravenous infusion of cis-dichlorodiammineplatinum (II). Over a 3-day period, less than 1% of the administered platinum was detected in the bile, and 47% appeared in the urine, indicating that biliary excretion is a minor route of elimination.