Possible role of 5-alpha reductase inhibitors in non-invasive bladder urothelial neoplasm: Multicentric retrospective study

Pastore, Antonio Luigi; Nunzio, Cosimo De; Salhi, Yazan Al; Fuschi, Andrea; Martoccia, Alessia; Velotti, G.; Amigoni, Nelia; Tubaro, Andrea; Artibani, Walter; Carbone, Antonio

doi:10.1016/s1569-9056(19)33551-1

Cited by 3 publications

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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 .…”

Section: Resultsmentioning

confidence: 99%

“…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 ).…”

Section: Resultsmentioning

confidence: 99%

“…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 ).…”

Section: Resultsmentioning

confidence: 99%

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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

et al. 2021

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Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30–0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22–0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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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

et al. 2021

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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: 89%

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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Impact of Androgen Suppression Therapy on the Risk and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis

Xiang

Hao

et al. 2021

Front. Oncol.

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PurposeThe purpose of this study was to summarize the existing evidence and develop a comprehensive systematic review of the impact of androgen suppression therapy (AST) on the incidence or clinical outcomes of bladder cancer.MethodsWe systematically searched the PubMed and Embase databases from inception to June 20, 2021 to identify all observational studies examining the incidence or clinical outcomes of bladder cancer in patients who received AST. AST is defined as the use of 5-alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT).ResultsA total of 18 observational studies were included. Our results showed that AST was not significantly associated with a reduced risk of BCa incidence (OR: 0.92, 95% CI: 0.68–1.24) compared with the lack of AST. The subgroup analysis revealed that finasteride use was significantly associated with a reduction in the risk of BCa incidence (OR: 0.75, 95% CI: 0.64–0.88). Recurrence-free survival (RFS) was improved among AST users compared with nonusers (HR: 0.68, 95% CI: 0.48–0.95), while no significant difference between AST users versus nonusers was identified for cancer-specific survival (CSS), overall survival (OS) or progression-free survival (PFS).ConclusionCurrent evidence indicates that therapy with finasteride may represent a potential strategy aimed at reducing BCa incidence. Moreover, AST has a beneficial effect on the recurrence of bladder cancer. Further well-designed randomized trials or cohort studies with better characterized study populations are needed to validate our preliminary findings.Systematic Review RegistrationInternational Prospective Register of Systematic Reviews database [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42021261685.

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Possible role of 5-alpha reductase inhibitors in non-invasive bladder urothelial neoplasm: Multicentric retrospective study

Cited by 3 publications

References 0 publications

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

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

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

Impact of Androgen Suppression Therapy on the Risk and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis

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