Bladder Cancer Survival of Men Receiving 5α-Reductase Inhibitors

Mäkelä, Ville; Kotsar, Andres; Tammela, Teuvo L.J.; Murtola, Teemu J.

doi:10.1016/j.juro.2018.04.082

Cited by 22 publications

(19 citation statements)

References 8 publications

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“…Kaplan-Meier analysis of recurrence-free survival with and without 5-ARI stratified by amount of BCG received: (A) Group I < 6 instillations (B) Group II < 1 year maintenance (C) Group III at least 1 year maintenance. who received 5-ARIs had a 25% reduction in disease specific survival compared to the control group who received ␣-blockers [12]. Finally, an evaluation of AR expression in bladder tumors from patients who also received androgen deprivation therapy suggests that these beneficial effects may be due to an AR-mediated effect of the loss of androgens [14].…”

Section: Discussionmentioning

confidence: 95%

“…In preclinical models the androgen receptor (AR) has been implicated in the development and progression of bladder cancer [6,7,11]. More recently, several clinical studies have suggested that men who receive 5-ARIs may have better bladder cancer outcomes [8,9,12,13]. Shiota et al demonstrated a reduced bladder cancer recurrence rates among patients who received 5-ARIs or androgen deprivation therapy in a cohort of 228 Japanese men [8].…”

Section: Discussionmentioning

confidence: 99%

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Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

Alhogbani

Gilbert

Lodde

et al. 2020

BLC

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BACKGROUND: Prior research implicates the androgen receptor pathway as important in bladder cancer progression and recurrence. In particular, use of 5-alpha reductase inhibitors (5-ARIs) appears to improve bladder cancer outcomes. This study aims to determine if concomitant use of 5-ARIs with intravesical Bacille Calmette-Guérin (BCG) decreases recurrences in patients with non-muscle invasive bladder cancer (NMIBC). MATERIALS & METHODS: This retrospective analysis included male patients diagnosed with NMIBC who were treated with induction intravesical BCG at our institution from 2013 to 2018. Patients were excluded who received prior induction BCG. Recurrence and progression-free survival were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards and Poisson events models. RESULTS: We identified 206 male patients, of whom 39 received 5-ARIs and 167 did not. Most patients (72.8%) received >6 instillations of BCG, with 20.4% completing all induction and maintenance treatments during a median follow up of 3.31 years. There were no significant differences in recurrence or progression-free survival between 5-ARI users or non-users (59% vs 55.7%; p = 0.72 and 97.4% vs 98.2%; p = 1.00, respectively). Similarly, no differences in the number of recurrences between groups was observed (p = 0.78). However, the proportion of patients who completed all prescribed BCG installations was higher among 5-ARI users (39.7% vs 17.9 %, p = 0.07). CONCLUSIONS: In contrast to prior reports, our study does not suggest that 5-ARI use decreases the recurrence rate in men receiving induction BCG for NMIBC. However, our results suggest 5-ARI use may improve patient tolerance to BCG.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

Alhogbani

Gilbert

Lodde

et al. 2020

BLC

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“…However, a study conducted by Ville et al has compared the bladder cancer specific mortality rate between 5-ARIs and α-blockers, a drug group that may also be affected by the same lead time bias with different medication mechanism. The risk reduction was only discovered in the 5-ARIs group, which indicated that lead time bias could not fully explain the decreased mortality rate [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

5α-reductase inhibitors impact prognosis of urothelial carcinoma

Wang

Juan

et al. 2020

BMC Cancer

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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.

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“…# P < 0.05 (vs. testosterone treatment).up demonstrated a significantly lower incidence of bladder cancer in men with finasteride treatment (1.07%) than in those without 5␣-RIs (1.46%) (hazard ratio 0.634; P = 0.0004)[18]. The beneficial effects of 5␣-RI therapy on the development and/or progression of bladder cancer have been further supported by a meta-analysis of 5 studies[30] as well as subsequent retrospective studies[20][21][22]. However, data from a double-blinded randomized clinical trial to determine if an ␣1-blocker doxazosin and/or finasteride could prevent the progression of BPH indicated no impact of 5␣-RI therapy (P = 0.67) on bladder cancer incidence in men with [9/1,216 (0.74%)] versus without [9/1,484 (0.61%)] finasteride treatment[19].…”

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confidence: 87%

5α-Reductase Inhibitors Do Not Prevent the Development and Progression of Urothelial Cancer: In Vitro Evidence

Nagata

Goto

Jiang

et al. 2020

BLC

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BACKGROUND: Androgen receptor (AR) activation has been implicated in the pathogenesis of urothelial cancer. However, it remains controversial whether 5α-reductase inhibitors (5α-RIs), which are known for blocking the conversion of testosterone to the more potent androgen dihydrotestosterone and often prescribed for the treatment of, for instance, benign prostatic hyperplasia, contribute to preventing the development of bladder cancer. OBJECTIVE: To determine the role of 5α-RI therapy in urothelial tumorigenesis and tumor progression, using cell line models. METHODS: In a human non-neoplastic urothelial SVHUC subline stably expressing a full-length wild-type human AR (SVHUC-AR) with carcinogen/MCA challenge and human bladder cancer lines, we assessed the effects of three 5α-RIs, dutasteride (up to 100 nM), finasteride (up to 500 nM), and epristeride (up to 5μM), on neoplastic/malignant transformation and cell growth, respectively. RESULTS: In AR-positive bladder cancer UMUC3 and 5637-AR cells, an AR antagonist bicalutamide significantly inhibited their proliferation, whereas three 5α-RIs failed to do. Similarly, these 5α-RIs did not significantly inhibit the migration of bladder cancer cells induced by the treatment of testosterone which could be metabolized into dihydrotestosterone in culture medium. In MCA-SVHUC-AR cells, induction of their neoplastic transformation by testosterone, which was prevented by bicalutamide, was confirmed. However, no significant inhibitory effects of 5α-RIs on the neoplastic transformation of AR-positive urothelial cells treated with or without testosterone were observed. CONCLUSIONS: Using in vitro models for urothelial cancer, 5α-RI treatment even at supra-pharmacological doses was thus found to have no significant impact on the prevention of both tumorigenesis and tumor progression.

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Bladder Cancer Survival of Men Receiving 5α-Reductase Inhibitors

Abstract: Patients who receive 5α-reductase inhibitors have improved disease specific survival after bladder cancer diagnosis compared to those who do not receive them while α-blockers were not associated with survival. This supports the benefits of 5α-reductase inhibitors in bladder cancer.

Cited by 22 publications

References 8 publications

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

Does 5-alpha Reductase Inhibitor Use Improve The Efficacy of Intravesical Bacille Calmette-Guérin (BCG) for Non-muscle Invasive Bladder Cancer?

5α-reductase inhibitors impact prognosis of urothelial carcinoma

5α-Reductase Inhibitors Do Not Prevent the Development and Progression of Urothelial Cancer: In Vitro Evidence

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