Assessment of Therapeutic Benefit and Option Strategy on Intravesical Instillation for Preventing Bladder Cancer Recurrence after Radical Nephroureterectomy in Patients with Upper Urinary Tract Urothelial Carcinoma.
Assessment of Therapeutic Benefit and Option Strategy on Intravesical Instillation for Preventing Bladder Cancer Recurrence after Radical Nephroureterectomy in Patients with Upper Urinary Tract Urothelial Carcinoma.
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上尿路尿路上皮癌根治性肾输尿管切除术后膀胱灌注预防膀胱癌复发的疗效评估和选择策略
DOI：
10.1155/2022/1755368
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发表时间：
2022
影响因子：
--
通讯作者：
Liu, Zhiyu
中科院分区：
文献类型：
--
作者：
Fan, Bo;Teng, Qiliang;Sun, Min;Wang, Yingzi;Wang, Yutong;Lin, Zhe;Wang, Yuchao;Duan, Xu;Zhang, Liren;Chen, Tingyu;Chen, Sishan;Tai, Yu;Zhang, Ce;Song, Xishuang;Liu, Zhiyu
上尿路尿路上皮癌(UUT-UC)是一种侵袭性很强的疾病，根治性肾输尿管切除术(RNU)后22%-50%的患者继发膀胱复发。虽然膀胱内灌注治疗能有效预防膀胱癌复发，但在东北中国地区尚无相关研究报道。有关RNU后膀胱内灌注的临床疗效的研究结果存在一定的争议，药物的最佳疗效和最小的不良反应还没有被广泛接受。本研究旨在系统评价膀胱内灌注预防膀胱癌复发的效果。在这项回顾性队列研究中，自2006年10月至2017年9月，158例UUT-UC患者接受RNU治疗，分为4组：表阿霉素(EPB)滴注组、羟基喜树碱(HCPT)滴注组、卡介苗(BCG)滴注组和未滴注组。采用COX单因素和多因素分析确定膀胱内无复发生存率(IVRFS)的危险因素。诺模图模型也被应用于预测患者的结果。随后，为了全面评价膀胱内灌注的临床意义，检索了PubMed、Ovid和Embase等数据库，并将已发表研究的数据与我们的结果进行了直接的Meta分析。此外，对不同的滴注疗法进行了网络Meta分析，以评价不同滴注药物的临床疗效。在我们的回溯性队列研究中，Kaplan-Meier生存曲线显示未灌注组与IVRFS恶化相关。多因素分析显示，膀胱内灌注是IVRFS的独立保护因素(危险比[HR] = 0.731)。此外，校准图、受试者工作特征(ROC)曲线、曲线下面积(AUC)值和C指数显示诺模图的预测准确性优先。接下来，包括19项研究的直接荟萃分析表明，膀胱内灌注可以预防膀胱癌的复发，合并风险比(RR)估计为0.53。根据研究类型、膀胱内复发年份、首次滴注时间和滴注次数进行的亚组分析也证实了结果的稳健性。此外，与术后滴注相比，术中滴注可降低膀胱复发的风险。然后，通过7篇研究的网络Meta分析表明，吡柔比星( = 89.2%)是降低膀胱癌复发风险最有效的药物，其次是卡介苗(Sucra = 83.5%)、丝裂霉素C(Sucra = 53.6%)、EPB(Sucra = 52.6%)和羟基喜树碱(Sucra = 5.1%)。UUT-UC患者RNU后维持膀胱内灌注的计划有效地预防了膀胱癌的复发。需要进行大规模的前瞻性试验，以进一步证实其价值。与其他化疗方案相比，THP有希望成为预防膀胱癌复发的有效药物。由于纳入的研究有中等的偏倚风险，网络荟萃分析的结果应谨慎应用。
Upper urinary tract urothelial carcinoma (UUT-UC) is a very aggressive disease, characterized by 22%–50% of patients suffering from subsequent bladder recurrence after radical nephroureterectomy (RNU). Although the therapy of intravesical instillation is reported to be effective in preventing bladder recurrence, no study had been reported in Northeast China. The findings relating to the clinical effectiveness of intravesical instillation after RNU are somewhat controversial, and the best efficacy and least adverse effects of instillation drugs have not been widely accepted. Here, we aimed at evaluating the efficacy of intravesical instillation for the prevention intravesical recurrence systematically. In this retrospective cohort study, from October 2006 to September 2017, 158 UUT-UC patients underwent RNU were divided into 4 groups: epirubicin (EPB) instillation group, hydroxycamptothecin (HCPT) instillation group, bacillus Calmette–Guerin (BCG) instillation group, and noninstillation group. Cox univariate and multivariate analyses were employed to identify the risk factors for intravesical recurrence-free survival (IVRFS). The nomogram model was also applied to predict patient outcomes. Subsequently, to evaluate the clinical significance of intravesical instillation comprehensively, several databases including PubMed, Ovid, and Embase were searched and data from published studies with our results were combined by direct meta-analysis. Moreover, a network meta-analysis comparing instillation therapies was conducted to evaluate the clinical efficacy of different instillation drugs. In our retrospective cohort study, the Kaplan–Meier survival curve demonstrated noninstillation groups were associated with worsened IVRFS. Meanwhile, multivariate analysis indicated that intravesical instillation was independent protective factors for IVRFS (hazard ratio [HR] = 0.731). Moreover, calibration plots, receiver operating characteristic (ROC) curves, area under the curve (AUC) values, and the C-index showed the priority of nomogram's predictive accuracy. Next, direct meta-analysis including 19 studies showed that intravesical instillation could prevent the recurrence of bladder cancer with a pooled risk ratio (RR) estimate of 0.53. Subgroup analysis by study type, year of intravesical recurrence, first instillation time, and instillation times also confirmed the robustness of the results. Moreover, intraoperative instillation was associated with a decrease in the risk of bladder recurrence compared with postoperative instillation. Then, a network meta-analysis including 7 studies indicated that pirarubicin (THP) (surface under the cumulative ranking curve [SUCRA] = 89.2%) is the most effective therapy to reduce the risk of bladder recurrence, followed by BCG (SUCRA = 83.5%), mitomycin C (MMC) (SUCRA = 53.6%), EPB (SUCRA = 52.6%), and HCPT (SUCRA = 5.1%) after the analysis of the value ranking. A maintenance schedule of intravesical instillation prevents the recurrence of bladder cancer after RNU in UUT-UC patients effectively. Large, prospective trials are needed to further confirm its value. Compared with other chemotherapy regimens, THP may be a promising drug with favorable efficacy to prevent bladder recurrence. As included studies had moderate risk of bias, the results of network meta-analysis should be applied with caution.
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影响因子：
4.5
作者：
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DOI：
10.1016/j.urolonc.2020.05.002
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