Martini Thomas, Wezel Felix, Löbig Niklas, Mitterberger Michael J, Colleselli Daniela
Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Deutschland.
Universitätsklinik für Urologie und Andrologie, Paracelsus Medizinischen Universität, Salzburg, Österreich.
Aktuelle Urol. 2017 Aug;48(4):314-328. doi: 10.1055/s-0043-108944. Epub 2017 Jun 13.
Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure. We performed a systematic search in the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, including all randomised controlled trials (RCTs), quasi-RCTs and single-arm studies, in which patients with NMIBC were treated with second-line intravesical or systemic therapy after BCG failure. A minimum of eight patients were included in each treatment arm. Full papers were restricted to English language. Literature research and data analysis were assessed independently by two reviewers. Data on treatment response, recurrence, time to recurrence, progression and rate of cystectomy were collected and analysed. This systematic review included 42 publications with a total of 3521 patients (2371 BCG failures). Valrubicin, taxanes, gemcitabine, combination chemotherapy, thermochemotherapy, photodynamic therapy, combination of BCG and interferon and immunotherapies or targeted therapies were identified as conservative treatment options. For taxanes, gemcitabine and thermochemotherapy there is the highest evidence for a clinical meaningful response with minor toxicities. Despite some promising response rates for taxanes, gemcitabine or thermochemotherapy, an evidence-based recommendation for treatment options superior to RC in patients failing BCG therapy cannot be made. The definition of BCG failure is still inconsistent and heterogeneous outcomes in patients with BCG failure have been reported. In order to identify effective conservative therapy options in patients failing BCG therapy, prospective trials with a standardised trial design are needed.
辅助性卡介苗（BCG）膀胱内灌注是高危非肌层浸润性膀胱癌（NMIBC）患者推荐的标准治疗方法。然而，相当一部分患者治疗失败，根治性膀胱切除术（RC）是后续的金标准。另一方面，对于不适合或不愿意接受手术的患者，保守替代方案仍未得到满足。本研究旨在确定卡介苗治疗失败后NMIBC患者的保守治疗方案。我们在Cochrane对照试验中央注册库（CENTRAL）、MEDLINE和EMBASE数据库中进行了系统检索，纳入了所有随机对照试验（RCT）、半随机对照试验和单臂研究，其中NMIBC患者在卡介苗治疗失败后接受二线膀胱内或全身治疗。每个治疗组至少纳入8例患者。全文仅限于英文。文献研究和数据分析由两名评审员独立评估。收集并分析了治疗反应、复发、复发时间、进展和膀胱切除术率的数据。这项系统评价纳入了42篇出版物，共3521例患者（2371例卡介苗治疗失败）。已确定缬更昔洛韦、紫杉烷、吉西他滨、联合化疗、热化疗、光动力疗法、卡介苗与干扰素联合疗法以及免疫疗法或靶向疗法为保守治疗方案。对于紫杉烷、吉西他滨和热化疗，有最高证据表明其具有临床意义的反应且毒性较小。尽管紫杉烷、吉西他滨或热化疗有一些令人鼓舞的反应率，但对于卡介苗治疗失败的患者，无法做出优于根治性膀胱切除术的基于证据的治疗方案推荐。卡介苗治疗失败的定义仍然不一致，并且已报道了卡介苗治疗失败患者的异质性结果。为了确定卡介苗治疗失败患者有效的保守治疗方案，需要采用标准化试验设计的前瞻性试验。
