5α-reductase inhibitors impact prognosis of urothelial carcinoma

Abstract

Background 5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database. Methods The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration. Results Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71–0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82–1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6–1.1). Conclusions Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don’t. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.

Inhibition of Androgen Signalling Improves the Outcomes of Therapies for Bladder Cancer: Results from a Systematic Review of Preclinical and Clinical Evidence and Meta-Analysis of Clinical Studies

“…Further assessment of eligibility, based on the study of the full-text papers, led to the exclusion of 44 papers. Finally, 14 studies (6 preclinical and 8 clinical) were included in the final analysis ( Figure 1 ) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Of these, 6 studies were included in the quantitative synthesis.…”

“…Overall, eight retrospective case-control studies were identified involving a total of 17,454 male patients [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. The study characteristics, patients’ demographics and tumour features are summarized in Table 2 .…”

“…BCa recurrence after TURBT was investigated in six studies [ 14 , 15 , 16 , 17 , 20 , 21 , 22 , 23 ]. The overall pooled data from these studies showed a statistically significant lower RR (RR: 0.50, 95% CI: 0.30–0.82, p = 0.006) in patients undergoing therapy with 5-ARIs or ADT compared to controls ( Figure 2 ).…”

“…Four studies included only patients undergoing therapy with 5-ARIs [ 17 , 21 , 22 , 23 ]. Pooled data from these studies confirmed a statistically significant lower RR of BCa recurrence (RR: 0.46 (95% CI: 0.22–0.95; p = 0.040) ( Figure 3 ).…”

“…BCa-related mortality was investigated in three studies [ 18 , 19 , 23 ]. In the study by Wang et al the number of deaths caused by BCa was 163 (34.39%) and 1873 (39.51%) in the 5-ARIs, and in the control group, respectively [ 23 ]. Compared to nonusers, patients who received 5-ARIs showed a lower risk of BCa death in multivariable adjusted analysis (Odds Ratio: 0.835, 95% CI: 0.71–0.98) [ 23 ].…”