Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer
Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer
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DOI：
10.1016/j.juro.2015.05.104
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发表时间：
2015-11-01
影响因子：
6.6
通讯作者：
Downs, Tracy M.
中科院分区：
文献类型：
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作者：
Blute, Michael L., Jr.;Rushmer, Timothy J.;Downs, Tracy M.
目的：先前的报道表明，抑制肾素-血管紧张素系统可以减少非肌层浸润性膀胱癌的复发。我们评估了初次手术时血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂治疗是否与减少非肌层浸润性膀胱癌患者的复发或进展有关。材料和方法：使用机构膀胱癌数据库，我们确定了340名具有初次经尿道膀胱肿瘤电切术数据的患者。进展定义为增加至T2期。考克斯比例风险模型被用来评估与复发和无进展survival.Results的关联：中位患者年龄为69.6岁。在中位随访3年（IQR 1.3-6.1）期间，200例患者（59%）复发，14例（4.1%）分期进展。在这些患者中，143例在首次经尿道切除术时正在接受血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂。在单变量分析中，与无复发生存率改善相关的因素包括原位癌（p = 0.040）、卡介苗治疗（p = 0.003）和血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂治疗（p = 0.009）。多变量分析表明，接受卡介苗治疗（HR 0.68，95% CI 0.47-0.87，p = 0.002）或血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂治疗（HR 0.61，95% CI 0.45-0.84，p = 0.005）的患者发生肿瘤复发的可能性较低。接受血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂治疗的患者的5年无复发生存率为45.6%，未接受血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂治疗的患者为28.1%（p = 0.009）。进行亚组分析，以评估非肌层浸润性膀胱癌的病理（Ta，T1和原位癌）在85例患者的卡介苗治疗单独和52人，它与血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂。多因素分析显示，单纯使用卡介苗治疗的患者（HR 2.19，95% CI 1.01-4.77，p = 0.04）显示，与卡介苗和血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂治疗的患者相比，（Ta期HR 0.45，95%CI 0.21-0.98，p = 0.04）。结论：药物抑制肾素-血管紧张素系统与膀胱癌患者预后改善相关。应在前瞻性随机试验中研究非肌层浸润性膀胱癌患者的肾素-血管紧张素系统抑制剂给药。
Purpose: Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer.Materials and Methods: Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival.Results: Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guerin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guerin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guerin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guerin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guerin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04).Conclusions: Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial.