Schmidt Stefanie, Kunath Frank, Coles Bernadette, Draeger Desiree Louise, Krabbe Laura-Maria, Dersch Rick, Kilian Samuel, Jensen Katrin, Dahm Philipp, Meerpohl Joerg J
UroEvidence@Deutsche Gesellschaft für Urologie, Martin-Buber-Str. 10, Berlin, Germany, 14163.
University Hospital Erlangen, Department of Urology, Krankenhausstrasse 12, Erlangen, Germany, 91054.
Cochrane Database Syst Rev. 2020 Jan 8;1(1):CD011935. doi: 10.1002/14651858.CD011935.pub2.
People with urothelial carcinoma of the bladder are at risk for recurrence and progression following transurethral resection of a bladder tumour (TURBT). Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) are commonly used, competing forms of intravesical therapy for intermediate- or high-risk non-muscle invasive (Ta and T1) urothelial bladder cancer but their relative merits are somewhat uncertain.
To assess the effects of BCG intravesical therapy compared to MMC intravesical therapy for treating intermediate- and high-risk Ta and T1 bladder cancer in adults.
We performed a systematic literature search in multiple databases (CENTRAL, MEDLINE, Embase, Web of Science, Scopus, LILACS), as well as in two clinical trial registries. We searched reference lists of relevant publications and abstract proceedings. We applied no language restrictions. The latest search was conducted in September 2019.
We included randomised controlled trials (RCTs) that compared intravesical BCG with intravesical MMC therapy for non-muscle invasive urothelial bladder cancer.
Two review authors independently screened the literature, extracted data, assessed risk of bias and rated the quality of evidence according to GRADE per outcome. In the meta-analyses, we used the random-effects model.
We identified 12 RCTs comparing BCG versus MMC in participants with intermediate- and high-risk non-muscle invasive bladder tumours (published from 1995 to 2013). In total, 2932 participants were randomised. Time to death from any cause: BCG may make little or no difference on time to death from any cause compared to MMC (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.79 to 1.20; participants = 1132, studies = 5; 567 participants in the BCG arm and 565 in the MMC arm; low-certainty evidence). This corresponds to 6 fewer deaths (40 fewer to 36 more) per 1000 participants treated with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Serious adverse effects: 12/577 participants treated with BCG experienced serious non-fatal adverse effects compared to 4/447 participants in the MMC group. The pooled risk ratio (RR) is 2.31 (95% CI 0.82 to 6.52; participants = 1024, studies = 5; low-certainty evidence). Therefore, BCG may increase the risk for serious adverse effects compared to MMC. This corresponds to nine more serious adverse effects (one fewer to 37 more) with BCG. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Time to recurrence: BCG may reduce the time to recurrence compared to MMC (HR 0.88, 95% CI 0.71 to 1.09; participants = 2616, studies = 11, 1273 participants in the BCG arm and 1343 in the MMC arm; low-certainty evidence). This corresponds to 41 fewer recurrences (104 fewer to 29 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations, imprecision and inconsistency. Time to progression: BCG may make little or no difference on time to progression compared to MMC (HR 0.96, 95% CI 0.73 to 1.26; participants = 1622, studies = 6; 804 participants in the BCG arm and 818 in the MMC arm; low-certainty evidence). This corresponds to four fewer progressions (29 fewer to 27 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Quality of life: we found very limited data for this outcomes and were unable to estimate an effect size.
AUTHORS' CONCLUSIONS: Based on our findings, BCG may reduce the risk of recurrence over time although the Confidence Intervals include the possibility of no difference. It may have no effect on either the risk of progression or risk of death from any cause over time. BCG may cause more serious adverse events although the Confidence Intervals once again include the possibility of no difference. We were unable to determine the impact on quality of life. The certainty of the evidence was consistently low, due to concerns that include possible selection bias, performance bias, given the lack of blinding in these studies, and imprecision.
膀胱尿路上皮癌患者在经尿道膀胱肿瘤切除术（TURBT）后有复发和进展的风险。丝裂霉素C（MMC）和卡介苗（BCG）是常用的、用于中高危非肌层浸润性（Ta和T1）膀胱尿路上皮癌的膀胱内治疗的竞争形式，但其相对优势尚不确定。
评估与MMC膀胱内治疗相比，BCG膀胱内治疗对成人中高危Ta和T1期膀胱癌的疗效。
我们在多个数据库（CENTRAL、MEDLINE、Embase、Web of Science、Scopus、LILACS）以及两个临床试验注册库中进行了系统的文献检索。我们检索了相关出版物的参考文献列表和摘要会议记录。我们没有设置语言限制。最新检索于2019年9月进行。
我们纳入了比较膀胱内BCG与膀胱内MMC治疗非肌层浸润性膀胱尿路上皮癌的随机对照试验（RCT）。
两位综述作者独立筛选文献、提取数据、评估偏倚风险，并根据GRADE对每个结局的证据质量进行评级。在荟萃分析中，我们使用随机效应模型。
我们确定了12项RCT，比较了BCG与MMC在中高危非肌层浸润性膀胱肿瘤患者中的疗效（发表于1995年至2013年）。共有2932名参与者被随机分组。任何原因导致的死亡时间：与MMC相比，BCG对任何原因导致的死亡时间可能几乎没有影响（风险比（HR）0．97，95％置信区间（CI）0．79至1．20；参与者＝1132，研究＝5；BCG组567名参与者，MMC组565名参与者；低质量证据）。这相当于每1000名接受BCG治疗的参与者在五年内死亡人数减少6人（减少40人至增加36人）。由于研究局限性和不精确性，我们将证据的确定性降低了两个等级。严重不良反应：接受BCG治疗的577名参与者中有12人发生严重非致命不良反应，而MMC组447名参与者中有4人发生。合并风险比（RR）为2．31（95％CI 0．82至6．52；参与者＝1024，研究＝5；低质量证据）。因此，与MMC相比，BCG可能会增加严重不良反应的风险。这相当于BCG组多了9例严重不良反应（减少1例至增加37例）。由于研究局限性和不精确性，我们将证据的确定性降低了两个等级。复发时间：与MMC相比，BCG可能会缩短复发时间（HR 0．88，95％CI 0．71至1．09；参与者＝2616，研究＝11，BCG组1273名参与者，MMC组1343名参与者；低质量证据）。这相当于BCG组在五年内复发次数减少41次（减少104次至增加29次）。由于研究局限性、不精确性和不一致性，我们将证据的确定性降低了两个等级。进展时间：与MMC相比BCG对进展时间可能几乎没有影响（HR 0．96，95％CI 0．73至1．26；参与者＝1622，研究＝6；BCG组804名参与者，MMC组818名参与者；低质量证据）。这相当于BCG组在五年内进展次数减少4次（减少29次至增加27次）。由于研究局限性和不精确性，我们将证据的确定性降低了两个等级。生活质量：我们发现关于这个结局的数据非常有限，无法估计效应大小。
根据我们的研究结果，随着时间的推移，BCG可能会降低复发风险，尽管置信区间包括无差异的可能性。随着时间的推移，它可能对进展风险或任何原因导致死亡的风险没有影响。BCG可能会导致更严重的不良事件，尽管置信区间再次包括无差异的可能性。我们无法确定其对生活质量的影响。由于存在可能的选择偏倚、实施偏倚（鉴于这些研究缺乏盲法）和不精确性等问题，证据的确定性一直很低。
