Lee Hsiang Ying, Lin Po-Hung, Pang See-Tong, Fang Jen-Kai, Tsai Chung-You, Tsai Yao-Chou, Chen Yung-Tai, Chen Wei-Chieh, Yeh Hsin-Chih, Li Wei-Ming
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Cancer Med. 2025 Jan;14(1):e70567. doi: 10.1002/cam4.70567.
Upper tract urothelial carcinoma (UTUC) presents a higher incidence rate in Taiwan compared to Western societies. The aim of this study is to investigate the potential of metformin in improving survival outcomes for patients with UTUC in Taiwan.
This retrospective study included 940 patients with UTUC and type 2 diabetes from the Taiwan UTUC Collaboration Group, spanning 21 hospitals from July 1988 to September 2023. Patients were divided into two groups: those treated with metformin (n = 215) and those without metformin treatment (n = 725). Parameters analyzed included age, BMI, renal function, tumor grade and location, and pathological staging. Oncological outcomes measured were overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS). Statistical analysis involved the use of Student's t-test, Mann-Whitney test, Chi-squared test, Fisher's exact test, and Cox proportional hazard regression.
Significant differences were observed between the two groups in BMI, preoperative creatinine, eGFR, tumor location, tumor laterality, tumor size, and pathological grade and T stage. Patients treated with metformin exhibited a lower risk of CSS (HR = 0.619; p = 0.018) and improved OS (HR = 0.713; p = 0.024), although no significant association was found with BRFS (HR = 1.034; p = 0.791). The protective effect of metformin on OS was particularly significant in patients with advanced T stage, metastasis, and high-grade tumors.
The study suggests that metformin use in UTUC patients with diabetes is associated with improved OS and CSS but not BRFS. The underlying mechanisms warrant further investigation. Repurposing metformin, a well-established and safe drug, may develop new therapeutic strategies for UTUC.
与西方社会相比，上尿路尿路上皮癌（UTUC）在台湾的发病率更高。本研究的目的是探讨二甲双胍对改善台湾UTUC患者生存结局的潜力。
这项回顾性研究纳入了台湾UTUC协作组的940例UTUC合并2型糖尿病患者，时间跨度为1988年7月至2023年9月，涉及21家医院。患者分为两组：接受二甲双胍治疗的患者（n = 215）和未接受二甲双胍治疗的患者（n = 725）。分析的参数包括年龄、体重指数、肾功能、肿瘤分级和位置以及病理分期。测量的肿瘤学结局包括总生存期（OS）、癌症特异性生存期（CSS）和无膀胱复发生存期（BRFS）。统计分析采用学生t检验、曼-惠特尼检验、卡方检验、费舍尔精确检验和Cox比例风险回归。
两组在体重指数、术前肌酐、估算肾小球滤过率（eGFR）、肿瘤位置、肿瘤侧别、肿瘤大小以及病理分级和T分期方面存在显著差异。接受二甲双胍治疗的患者CSS风险较低（HR = 0.619；p = 0.018），OS有所改善（HR = 0.713；p = 0.024），尽管未发现与BRFS有显著关联（HR = 1.034；p = 0.791）。二甲双胍对OS的保护作用在晚期T分期、转移和高级别肿瘤患者中尤为显著。
该研究表明，糖尿病UTUC患者使用二甲双胍与改善OS和CSS相关，但与BRFS无关。其潜在机制值得进一步研究。重新利用二甲双胍这种成熟且安全的药物，可能为UTUC开发新的治疗策略。
