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.
The MerativeTM 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.
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.
The use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.
Urologic oncology. 2024 Sep 06 [Epub ahead of print]
Francesco Del Giudice, Łukasz Nowak, Frank Glover, Albert Ha, Michael Scott, Federico Belladelli, Satvir Basran, Shufeng Li, Evan Mulloy, Benjamin Pradere, Vincenzo Asero, Jan Łaszkiewicz, Wojciech Krajewski, Rajesh Nair, Michael L Eisenberg
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. Electronic address: ., Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50 367 Wrocław, Poland., Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA,USA., Department of Urology, Stanford University School of Medicine, Stanford, CA, USA., Department of Urology, Stanford University School of Medicine, Stanford, CA, USA; University Vita-Salute San Rafaele, Milan, Italy; Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS San Raffaele Hospital, Milan, Italy., Department of Urology, Stanford University School of Medicine, Stanford, CA, USA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA., Department of Urology, Croix Du Sud Hospital, Quint-Fonsegrives, France., 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, Guys and St, Thomas' NHS Foundation Trust, London, UK.