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
Authors: Shelley M.D. , Wilt T.J. , Court J. , Coles B. , Kynaston H. , Mason M.D. 
Published: February 2004

The 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 that there was indeed a strong association between infection with this virus and a considerable proportion of primary urothelial TCCs.

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.