Nayan Madhur, Bhindi Bimal, Yu Julie L, Hermanns Thomas, Mohammed Aza, Hamilton Robert J, Finelli Antonio, Jewett Michael A S, Zlotta Alexandre R, Fleshner Neil E, Kulkarni Girish S
Department of Surgery, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada; Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada.
Department of Surgery, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada; Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada.
Urol Oncol. 2015 Sep;33(9):386.e7-13. doi: 10.1016/j.urolonc.2015.05.024. Epub 2015 Jun 19.
Metformin, a first-line oral therapy for diabetes, has anticancer properties. Our objective was to evaluate the association between metformin use and oncologic outcomes in diabetic patients undergoing radical cystectomy (RC) for bladder cancer (BC).
A single-institution retrospective cohort (January 1997-June 2013) of diabetic patients undergoing RC was assembled. Medication use was assessed at time of surgery. Outcome measures were recurrence-free survival (RFS), BC-specific survival (BCSS), and overall survival (OS). Multivariable Cox proportional hazards models were used. To create parsimonious models, the change of estimate approach (10% threshold) was used as a variable selection strategy for final model inclusion separately for each outcome measure.
Of 421 patients, 85 (20%) had diabetes. There were 39 (46%) patients on metformin therapy. Among diabetic patients, there were 21 patients with BC recurrence, 16 who died of BC, and 30 who died overall. In univariate analyses, metformin use among diabetic patients was associated with improved RFS (hazard ratio = 0.54, 95% CI: 0.33-0.88, P = 0.013) and trended toward improved BCSS (hazard ratio = 0.65, 95% CI: 0.40-1.07, P = 0.087), but not with OS (P = 0.87). In multivariable models, metformin use among diabetic patients was associated with significantly improved RFS (adjusted hazard ratio = 0.38, 95% CI: 0.20-0.72, P = 0.003) and BCSS (adjusted hazard ratio = 0.57, 95% CI: 0.35-0.91, P = 0.019), but not with OS (P = 0.89). Use of other oral hypoglycemic agents or insulin was not associated with oncologic outcomes.
Our study is among the first to report an association between metformin use and improved RFS and BCSS in diabetic patients undergoing RC. Given its low cost and demonstrated safety among nondiabetic patients, further studies are warranted to evaluate potential therapeutic and preventive roles of metformin in BC.
二甲双胍是糖尿病的一线口服治疗药物，具有抗癌特性。我们的目的是评估在接受膀胱癌根治性膀胱切除术（RC）的糖尿病患者中，使用二甲双胍与肿瘤学结局之间的关联。
收集了一家机构中接受RC的糖尿病患者的单机构回顾性队列（1997年1月至2013年6月）。在手术时评估药物使用情况。结局指标为无复发生存期（RFS）、膀胱癌特异性生存期（BCSS）和总生存期（OS）。使用多变量Cox比例风险模型。为创建简约模型，采用估计值变化法（10%阈值）作为变量选择策略，分别针对每个结局指标纳入最终模型。
421例患者中，85例（20%）患有糖尿病。39例（46%）患者接受二甲双胍治疗。在糖尿病患者中，有21例发生膀胱癌复发，16例死于膀胱癌，30例死亡。在单因素分析中，糖尿病患者使用二甲双胍与改善RFS相关（风险比=0.54，95%CI：0.33 - 0.88，P = 0.013），且有改善BCSS的趋势（风险比=0.65，95%CI：0.40 - 1.07，P = 0.087），但与OS无关（P = 0.87）。在多变量模型中，糖尿病患者使用二甲双胍与显著改善RFS（调整后风险比=0.38，95%CI：0.20 - 0.72，P = 0.003）和BCSS（调整后风险比=0.57，95%CI：0.35 - 0.91，P = 0.019）相关，但与OS无关（P = 0.89）。使用其他口服降糖药或胰岛素与肿瘤学结局无关。
我们的研究是首批报告在接受RC的糖尿病患者中，使用二甲双胍与改善RFS和BCSS之间存在关联的研究之一。鉴于其成本低且在非糖尿病患者中已证明的安全性，有必要进一步研究评估二甲双胍在膀胱癌中的潜在治疗和预防作用。
