Intravesical Bacillus Calmette-Guerin Versus Mitomycin C For Superficial Bladder Cancer: A Formal Meta-Analysis of Comparative Studies on Recurrence and Toxicity

Department of Urology, Medical University of Lübeck, Lübeck, Germany.
The Journal of Urology (Impact Factor: 3.75). 01/2003; 169(1):90-5. DOI: 10.1097/01.ju.0000039680.90768.b3
Source: PubMed

ABSTRACT We compare the therapeutic efficacy and toxicity of intravesical bacillus Calmette-Guerin (BCG) with mitomycin C on recurrence of stages Ta and T1 bladder carcinoma.
Combined published and unpublished data from comparative studies on BCG versus mitomycin C for superficial bladder carcinoma considering possible confounding factors were analyzed. Odds ratio (OR) and its 95% CI were used as primary effect size estimate. Toxicity data were evaluated descriptively.
In 11 eligible clinical trials 1,421 patients were treated with BCG and 1,328 were treated with mitomycin C. Within the overall median followup time of 26 months 38.6% of the patients in the BCG group and 46.4% of those in the mitomycin C group had tumor recurrence. In 7 of 11 studies BCG was significantly superior to mitomycin C, in 3 studies no significant difference was found, while in 1 study mitomycin C was significantly superior to BCG. An overall statistically significant superiority of BCG versus mitomycin C efficacy in reducing tumor recurrence was detected (OR 0.56, 95% CI 0.38 to 0.84, p = 0.005). In the subgroup treated with BCG maintenance all 6 individual studies showed a significant superiority of BCG over mitomycin C (OR 0.43, 95% CI 0.35 to 0.53, p <0.001). In 4 of the 5 studies with reported data on toxicity BCG associated cystitis was significantly more frequent than in the mitomycin C group (53.8% versus 39.2%). The combined cystitis OR was 1.81 (95% CI 1.48 to 2.23, p <0.001). The OR for cystitis in the BCG maintenance group did not significantly differ from that in the nonmaintenance therapy group.
The results suggest superiority of BCG over mitomycin C for prevention of tumor recurrences in the combined data and particularly in the BCG maintenance treatment subgroup, irrespective of the actual (intermediate or high) tumor risk status. The toxicity with BCG is higher but does not differ between BCG maintenance and nonmaintenance groups.

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    • "In contrast, patients who were able to tolerate BCG and had an initial response were reported to have a 38.6% recurrence rate after a median follow-up of 26 months [46]. BCG unresponsiveness is defined as persistent high grade tumor at 6 months or a recurrence within 6 months or less after achieving a disease-free state [47] [48]. "
    04/2015; 1(1):15-27. DOI:10.3233/BLC-150014
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    • "En revanche, la fréquence des effets secondaires n'a pas a été augmentée en cas de traitements d'entretien. La méta-analyse de Böhle et al. a montré que la fréquence des syndromes irritatifs vésicaux n'était pas différente selon que les patients reçoivent ou pas un traitement d'entretien [31] (niveau de preuve 1). Dans une étude de phase III comparant deux groupes de 320 et 319 patients traités respectivement sans et avec traitement d'entretien, Van der Meijden et al. ont objectivé que la majorité des EI locorégionaux et généraux survenaient durant le traitement d'induction par BCG et n'étaient pas corrélés au nombre d'instillations réalisées dans le cadre du traitement d'entretien [32] (niveau de preuve 1). "
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    ABSTRACT: BCG therapy, which is the standard treatment for non-muscle invasive bladder tumours with high risk of recurrence and progression, has potential life-threatening adverse effects (AEs). Rapid deterioration of general condition in a patient with history of bladder tumour should question about an ongoing treatment with BCG and specify the date of the last instillation. Trauma during catheterization and untreated concomitant urinary infection upon instillations are risk factors of severe AEs. In emergency, the diagnosis of severe AEs of BCG therapy is only based on the medical questioning with the notion of current BCG treatment and risk-bearing event upon instillation. Management of AEs is related to their pathophysiological mechanisms and relies on a combination of antibiotics against BCG, the symptomatic treatment, and corticosteroid therapy which has shown to improve patient outcomes.
    La Presse Médicale 02/2013; 42(7-8). DOI:10.1016/j.lpm.2012.10.017 · 1.17 Impact Factor
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    • "Advances in Urology this therapeutic, which may result in tumour progression [5] [6] [7] [8] [9]. Other important fact related with BCG treatment is that 90% of patients will experience some sort of side effects (local cystitis symptoms such dysuria, frequency alteration, and occasional haematuria) [10] [11] and, for this reason, an elevated number of patients did not complete the treatment schedule [12] [13] although a significant higher withdrawal rate of patients treated with BCG could not be demonstrated [12] [13] [14]. Since the response to BCG is unpredictable, it is important to find a reliable predictive biomarker and/or a marker that could identify elevated risk groups of treatment failure and side effects development. "
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    ABSTRACT: The most effective therapeutic option for managing nonmuscle invasive bladder cancer (NMIBC), over the last 30 years, consists of intravesical instillations with the attenuated strain Bacillus Calmette-Guérin (the BCG vaccine). This has been performed as an adjuvant therapeutic to transurethral resection of bladder tumour (TURBT) and mostly directed towards patients with high-grade tumours, T1 tumours, and in situ carcinomas. However, from 20% to 40% of the patients do not respond and frequently present tumour progression. Since BCG effectiveness is unpredictable, it is important to find consistent biomarkers that can aid either in the prediction of the outcome and/or side effects development. Accordingly, we conducted a systematic critical review to identify the most preeminent predictive molecular markers associated with BCG response. To the best of our knowledge, this is the first review exclusively focusing on predictive biomarkers for BCG treatment outcome. Using a specific query, 1324 abstracts were gathered, then inclusion/exclusion criteria were applied, and finally 87 manuscripts were included. Several molecules, including CD68 and genetic polymorphisms, have been identified as promising surrogate biomarkers. Combinatory analysis of the candidate predictive markers is a crucial step to create a predictive profile of treatment response.
    Advances in Urology 08/2012; 2012(5):232609. DOI:10.1155/2012/232609
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