Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan.
Eur Urol Focus. 2022 Mar;8(2):447-456. doi: 10.1016/j.euf.2021.03.016. Epub 2021 Mar 21.
Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment.
To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC.
The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy.
Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26-1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39-2.11 vs OR 0.93, 95% CI 0.40-2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666).
Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression.
A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.
对于没有明确循证决策树的中危非肌肉浸润性膀胱癌（NMIBC）患者，可能存在临床困境。
进行系统评价和网络荟萃分析（NMA），以总结中危 NMIBC 患者膀胱内治疗的肿瘤学结局的现有证据。
根据系统评价和荟萃分析的首选报告项目声明，于 2020 年 10 月检索 MEDLINE、EMBASE 和 ClinicalTrials.gov 数据库。如果研究报告了接受经尿道膀胱肿瘤切除术联合和不联合膀胱内化疗或卡介苗（BCG）免疫治疗的中危 NMIBC 患者的肿瘤学结局，则认为其符合纳入标准。
12 项研究纳入定性综合（系统评价）；其中 3 项研究被认为适合进行定量综合（NMA）。对五种不同方案的治疗与 5 年复发风险的关系进行了 NMA。与无维持化疗相比，化疗联合维持治疗 5 年复发的可能性较低（比值比[OR]0.51，95%可信区间[CI]0.26-1.03）。与无维持化疗相比，免疫治疗（无论全剂量还是低剂量方案）与 5 年复发的可能性显著降低无关（OR0.90，95%CI0.39-2.11 与 OR0.93，95%CI0.40-2.19）。治疗排序分析表明，维持化疗方案具有最低的 5 年复发风险（P 评分 0.9666）。
我们的分析表明，与无维持化疗相比，中危 NMIBC 患者接受维持化疗方案治疗可显著降低 5 年复发风险。无论剂量方案如何，BCG 免疫疗法在中危 NMIBC 患者中的疗效似乎并不优于化疗。然而，由于缺乏比较研究，因此需要进行精心设计的大规模试验来验证我们的研究结果，并为疾病复发和进展提供有力的证据。
维持化疗方案可降低未侵犯膀胱肌肉的膀胱癌长期复发率。直接膀胱内插入化疗和无维持化疗方案的免疫治疗似乎对预防癌症复发的效果有限。
