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-Guérin (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.
To undertake a systematic review and meta-analysis comparing intravesical mitomycin C and Bacillus Calmette-Guérin in terms of tumour recurrence, disease progression and overall survival in Ta and T1 bladder cancer. Treatment-related toxicities would also be evaluated.
A comprehensive search of MEDLINE, EMBASE, Healthstar, Cochrane Controlled Trials Register, Cancerlit, and DARE was performed, and hand searching of relevant journals undertaken.
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.
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 13.5 mg) compared to a standard dose of mitomycin C (30 mg), and reported a significantly reduced recurrent 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.
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.
膀胱內Bacillus CalmetteGuerin與Mitomycin C用於Ta及T1膀胱癌之比較
Ta及T1期之膀胱癌經尿道切除後之腫瘤復發，是重要之臨床問題。膀胱內投予mitomycin C (MMC)或bacillus CalmetteGuerin (BCG) 已證實具有預防的效果，但兩者都會帶來局部或全身的不良反應。本文即是對這兩種藥物的功效，進行系統性的回顧。
對MEDLINE, EMBASE, Healthstar, Cochrane Controlled Trials Register、Cancerlit、及DARE進行廣泛搜尋，並且手動搜尋相關期刊。
試驗的妥適性、方法學品質及資料採擷由兩位回顧者獨立評估。使用log hazard ratio進行timetoevent analysis，並依病人的復發風險，進行敏感度分析。
有25篇文章被搜尋到，但只有7篇堪稱可用。總共有1,901名病患可評估，其中820名被分派至MMC，而1,081名至BCG。共6個試驗具有足夠的資料進行統合分析，包含1,527名病患，其中693名被分派至MMC，而834名至BCG組。6個試驗中,腫瘤復發的加權後平均log hazard ratio (變異數) 是0.022 (0.005) ，亦即MMC及BCG之間並無顯著差異(p = 0.76)。然而，統合分析指出各試驗之間存有顯著的差異 (p = 0.001)。3個僅包含高危險Ta及T1病患試驗的次群體分析指出，彼此試驗設計上差異不大 (p = 0.25)，因此統合分析可看出復發的log hazard ratio (變異數)是 −0.371 (0.012)。若以MMC為對照，負值的比率表示BCG組較優，而且十分顯著 (p = 0.0008)。第7個試驗，僅為摘要形式，使用兩組低劑量BCG (27 mg及13.5 mg)，與標準劑量之MMC (30 mg)比較，發現使用BCG (27 mg) 比起MMC，復發率顯著降低 (p = 0.001)。只有2個試驗包含足以分析疾病進展及存活的資料，總共681名病患，338名隨機分派至BCG，343名至MMC組。MMC與BCG之間，對疾病進展 (log hazard ratio + 變異數: 0.044 + 0.04, p = 0.16) 及存活期 (log hazard ratio + 變異數: −0.112 + 0.03, p = 0.50) 皆無顯著差異。膀胱局部毒性(解尿疼痛、膀胱炎、頻尿、及血尿)在MMC (30%) 及BCG (44%) 皆可看到。全身性毒性，如寒顫、發燒及疲倦，在MMC及BCG皆有發現(各為12%及19%)，然而皮疹較常見於MMC。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。