5α-还原酶抑制剂联合或不联合α受体阻滞剂与良性前列腺增生男性发生上尿路尿路上皮癌的风险：美国保险理赔数据分析
5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data.
作者信息
Del Giudice Francesco, Nowak Łukasz, Glover Frank, Ha Albert, Scott Michael, Belladelli Federico, Basran Satvir, Li Shufeng, Mulloy Evan, Pradere Benjamin, Asero Vincenzo, Łaszkiewicz Jan, Krajewski Wojciech, Nair Rajesh, Eisenberg Michael L
机构信息
Department of Maternal Infant and Urologic Sciences, "Sapienza" University of Rome, Policlinico Umberto I Hospital, Rome, Italy. Viale del Policlinico 155, 00161, Rome, Italy; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50 367 Wrocław, Poland.
出版信息
Urol Oncol. 2025 Apr;43(4):266.e9-266.e16. doi: 10.1016/j.urolonc.2024.07.018. Epub 2024 Sep 7.
BACKGROUND
Increasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database.
METHODS
The Merative Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time.
RESULTS
Overall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58-1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87-1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods.
CONCLUSIONS
The use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.
背景
越来越多的数据表明，雄激素受体信号传导可能在尿路上皮癌的致癌过程中起重要作用。虽然已经探讨了5α还原酶抑制剂（5-ARi）对良性前列腺增生（BPH）男性膀胱癌风险的化学保护作用，但结果相互矛盾，关于5-ARi治疗以及上尿路尿路上皮癌（UTUC）发生风险的证据仍然缺乏。因此，我们的目标是使用一个大型美国数据库来研究5-ARi给药对新UTUC病例发生率的影响。
方法
使用默克多市场扫描数据库（Merative Marketscan®）来识别2007年至2021年间年龄≥50岁、诊断为BPH且正在使用5-ARi的男性，并随后与配对对照进行匹配。采用多变量Cox回归模型来确定5-ARi和/或α受体阻滞剂（α-B）药物与UTUC发生率之间的关联。基于暴露风险（以2年为阈值）进行了额外的亚组分析，以研究5-ARi与UTUC随时间的关系。
结果
总体而言，识别出n = 1,103,743名无BPH处方的BPH男性、n = 31,142名使用5-ARi的男性以及n = 160,049名使用5-ARi + α-B的男性。在随访期间，共有n = 4,761名患者被诊断为UTUC。匹配后，未接受积极BPH治疗的男性中UTUC发生率为0.36%至0.41%，而5-ARi组和5-ARi + α-B组分别为0.30%和0.52%。在多变量分析中，无论是5-ARi单药治疗（调整后风险比[aHR]：0.91，95%置信区间[CI]：0.58 - 1.44）还是5-ARi + α-B联合治疗（aHR：1.02，95% CI：0.87 - 1.19），均未观察到对UTUC风险的化学保护作用。在短期（≤2年）和长期（>2年）随访期内均是如此。
结论
使用5-ARi治疗BPH，无论是单独使用还是与α-B联合使用，均与UTUC的发生无关。
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