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

Abstract

OBJECTIVETo 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. METHODSThe 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. RESULTSTwenty-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%). SystemicThe first paper in this section is a meta-analysis of randomized trials into the effect of two intravesical agents used to reduce tumour recurrence in high-risk superficial bladder cancer. This is the highest level of evidence-based medicine and the results presented here suggest that intravesical BCG is superior to mitomycin C. There was no difference in the effect of the two agents on disease progression or survival. In a study from Amsterdam and Rome, the authors describe a phase I trial into the toxicity and safety of intravesical gemcitabine, and found that it was well tolerated with no systemic toxicity.In a paper from Taiwan the link between viral infections and tumour foundation is evaluated, in this case specifically infections with the Epstein-Barr virus and its correlation with urothelial cancer. The authors found ...

An Individual Patient Data Meta-Analysis of the Long-Term Outcome of Randomised Studies Comparing Intravesical Mitomycin C versus Bacillus Calmette-Guérin for Non–Muscle-Invasive Bladder Cancer

“…Several meta-analyses have dealt with this comparison. The Cochrane group performed a meta-analysis of seven trials and concluded that tumour recurrence was significantly reduced with BCG only in the subgroup of patients at high risk of tumour recurrence [8]. This finding is in contrast to another metaanalysis that suggested the superiority of BCG over MMC for prevention of tumour recurrence in the combined data, and particularly in the subgroup of patients treated with maintenance BCG, regardless of the actual tumour risk group (intermediate or high risk) [5].…”

Câncer de bexiga: estadiamento e tratamento I

“…Outra revisão comparativa mostrou que o BCG apresentou menor taxa de recorrência que a mitomicina C, sendo o agente mais recomendado para a terapia intravesical no regime seqüencial 16 (A), principalmente nos casos de carcinoma in situ. O momento do início do tratamento, dose, número de aplicações, intervalo entre as aplicações e tempo de permanência da droga na bexiga foram estabelecidos empiricamente.…”

“…Os efeitos colaterais mais freqüentes foram: disúria, cistite, polaciúria e hematúria. As complicações sistêmicas são febre, calafrios, indisposição e rash cutâneo 16 (A) 18 (B).…”

Immunotherapy of transitional cell carcinoma of urinary bladder

“…Postoje razne sheme za terapiju održavanja, no najčešće se aplicira kroz tri tjedna u određenim mjesečnim intervalima (3-ili 6-mjesečnim). Najveća vrijednost intravezikalne aplikacije BCG-om je smanjenje rizika od recidiva i progresije bolesti [16][17][18] . Neke studije navode i produženje stope preživljenja u oboljelih od karcinoma mjehura uz BCG imunoterapiju.…”

“…53, No. 3, p. 314-319 ljiva je veća uspješnost BCG terapije, ali i veća stopa nuspojava uz BCG terapiju [16][17][18] . Carcinoma in situ (CIS) predstavlja dijagnostički i terapijski izazov 19 .…”