The efficacy of post-TURBT intravesical BCG was evaluated in a Cochrane database review which compared tumour recurrence following TURBT with TURBT plus intravesical BCG for patients with stage Ta and T1 disease. In six randomised trials involving 585 eligible patients, there were significantly fewer recurrences at 12 months in the TURBT plus BCG group compared to those receiving TURBT alone (odds ratio 0.30, 95% confidence interval {CI} 0.21 to 0.43).r
Han and Panr also conducted a meta-analysis to determine whether intravesical BCG reduced recurrence after transurethral resection of superficial bladder cancer. They searched 176 trials, and identified 25 trials with recurrence information on 4767 patients. Of 2342 patients undergoing BCG therapy, 949 (40.5%) had tumour recurrence compared with 1205 (49.7%) of the 2425 patients in the non-BCG group. In the combined results, a statistically significant difference in the OR for tumour recurrence between the BCG and the non BCG-treated groups was found (randomised combined effect OR 0.61, 95% CI 0.46 to 0.80, P<0.0001). Stratified by BCG maintenance and disease type, the combined results of the individual reports showed statistically significance for BCG maintenance (OR 0.47, 95% CI 0.28 to 0.78, P=004) and treatment for papillary carcinoma (OR 0.50, 95% CI 0.33 to 0.75, P=0.0008). Chemotherapy + BCG plus chemotherapy/immunotherapy were not better than BCG alone. They concluded that adjuvant intravesical BCG with maintenance treatment is effective for the prophylaxis of tumour recurrence in superficial bladder cancer. For patients with papillary carcinoma, adjuvant intravesical BCG with maintenance therapy should be offered.r
Another systematic review of intravesical BCG compared to mitomycin-C (MMC) has been done by Shelley and Court et al.r They reviewed 25 articles but only 7 were considered eligible. This represented 1901 evaluable patients in total, 820 randomised to MMC and 1081 to BCG. 6 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 13.5 mg) compared to a standard dose of mitomycin C (30 mg), and reported a significantly reduced recurrence rate with BCG (27 mg) 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.r
Efficacy
Disease free survival in all patientsr:
© Journal of Urology 1999
Toxicity
Toxicityr |
BCG
n=585 (%) |
Urinary frequency |
71 |
Cystitis |
67 |
Fever |
25 |
Haematuria |
23 |
Flu-like illness |
15 |
Malaise |
14 |
Allergic symptoms |
10 |
Nausea |
8 |
Epididymitis |
6 |
Prostatitis |
3 |
Contracted bladder |
2 |
BCG sepsis |
0 |
Deaths |
0 |