Quan Yongjun, Jeong Chang Wook, Kwak Cheol, Kim Hyeon Hoe, Kim Hyung Suk, Ku Ja Hyeon
Department of Urology, Seoul National University Hospital, Seoul Department of Urology, Dongguk University Ilsan Medical Center, Goyang, Korea.
Medicine (Baltimore). 2017 Oct;96(42):e8300. doi: 10.1097/MD.0000000000008300.
Intravesical bacillus Calmette-Guerin (BCG) instillation is widely used as an adjuvant therapy after transurethral resection of bladder tumor (TURBT) in patients with intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC). However, the effective dose, duration, and strain of BCG have not yet been clearly determined. We aimed to elucidate the relationship between dose, duration, and strain of BCG and clinical outcomes in NMIBC patients treated with TURBT.
We conducted a literature search in Embase, Scopus, and PubMed databases for all relevant articles published up to October 2016 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The relative risks of clinical outcomes, including recurrence, progression, cancer-specific mortality, and all-cause mortality according to dose (standard vs low), duration (induction vs maintenance), and strain of BCG were presented as the pooled risk ratio (RR) and 95% confidence interval (CI).
Nineteen studies meeting the inclusion criteria were finally selected in this meta-analysis. The risk of recurrence was significantly highly observed in case of low-dose BCG (RR, 1.17; 95% CI 1.06-1.30) and induction BCG (RR, 1.33; 95% CI 1.17-1.50) only group without heterogeneity among the included studies. Although there were no significant differences between dose or duration and other clinical outcomes. On direct comparison in each study comparing BCG strains, the Tice stain showed a relatively high probability of recurrence compared with the Connaught (RR, 1.29; 95% CI 1.01-1.64) and RIVM (RR, 2.04, 95% CI 1.28-3.25) strains. Funnel plot testing revealed no significant publication bias.
The use of standard dose and maintenance BCG instillation may be effective to reduce recurrence rate after TURBT for NMIBC. Further large scale, well-designed, and prospective studies, with stratification of the patients into risk group at randomization, will be required to determine the optimal guideline of BCG use to improve clinical outcomes in NMIBC.
膀胱内灌注卡介苗（BCG）广泛用于中高危非肌层浸润性膀胱癌（NMIBC）患者经尿道膀胱肿瘤切除术（TURBT）后的辅助治疗。然而，BCG的有效剂量、疗程和菌株尚未明确确定。我们旨在阐明BCG的剂量、疗程和菌株与接受TURBT治疗的NMIBC患者临床结局之间的关系。
我们按照系统评价和Meta分析的首选报告项目指南，在Embase、Scopus和PubMed数据库中检索了截至2016年10月发表的所有相关文章。根据BCG的剂量（标准剂量与低剂量）、疗程（诱导与维持）和菌株，将包括复发、进展、癌症特异性死亡率和全因死亡率在内的临床结局的相对风险表示为合并风险比（RR）和95%置信区间（CI）。
本Meta分析最终纳入了19项符合纳入标准的研究。仅在低剂量BCG组（RR，1.17；95%CI 1.06-1.30）和诱导BCG组（RR，1.33；95%CI 1.17-1.50）观察到复发风险显著升高，纳入研究之间无异质性。虽然剂量或疗程与其他临床结局之间无显著差异。在每项比较BCG菌株的研究中直接比较发现，与康诺特菌株（RR，1.29；95%CI 1.01-1.64）和荷兰国家公共卫生与环境研究所菌株（RR，2.04，95%CI 1.28-3.25）相比，Tice菌株显示出相对较高的复发概率。漏斗图检验未发现显著的发表偏倚。
使用标准剂量和维持性BCG灌注可能有效降低NMIBC患者TURBT后的复发率。需要进一步开展大规模、设计良好的前瞻性研究，并在随机分组时将患者分层为风险组，以确定BCG使用的最佳指南，从而改善NMIBC的临床结局。
