Receipt of 5-Alpha Reductase Inhibitors Before Radical Cystectomy: Do They Render High-Grade Bladder Tumors Less Aggressive?

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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“…However, McMartin et al. ( 26 ) failed to find a significant difference in RFS between patients undergoing therapy with 5-ARIs and controls.…”

Section: Resultsmentioning

confidence: 97%

“…Eight studies evaluated the effect of AST on bladder cancer incidence ( 22 , 27 , 28 , 30 , 32 – 34 , 38 ). Ten studies examined the effect of AST on bladder cancer recurrence, progression and survival ( 21 , 23 – 26 , 29 , 31 , 35 – 37 ). The characteristics of the selected studies were summarized in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

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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“…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%

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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“…There is an interesting study to assess whether receipt of 5-alpha reductase inhibitors (5-ARIs) influenced the findings on surgical pathology at the time of RC and subsequent clinical outcomes. [ 82 ] The study cohort included 338 men; 48 patients (14%) were receiving dutasteride or finasteride at the time of RC, 58 (17%) metformin, and 195 (58%) statins. Among patients receiving 5-ARIs, there was a lower proportion of positive margins ( P = 0.08) and lymphovascular invasion ( P = 0.05).…”

Section: What Are the Therapeutic Implications Of Sex Steroid Hormonementioning

confidence: 99%

Clinical and therapeutic implications of sex steroid hormone receptor status in urothelial bladder cancer

2020

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Studies on the clinical profile of urothelial bladder cancer (UBC) have shown significant gender differences, namely, higher occurrence in males (male-to-female ratio of 3.5:1) and an advanced stage of disease at the time of diagnosis with rapid progression of the disease after initial diagnosis seen more commonly in females. The relationship between gender and UBC is complex and probably influenced by biological and epidemiological factors. Potential contributory factors such as sex steroid hormone pathway, gender difference in environmental carcinogen exposure, metabolic enzyme activity, and disparities in the intensity of diagnostic evaluation could probably explain the demographic trends in UBC. This comprehensive review of Medline publications during the period 2009–2019 attempts to identify the possible role of sex hormone receptors in gender variation and sexual dimorphism in the occurrence and progression of UBC. The clinical implications of identifying sex steroid receptors on factors such as disease prognostication and the therapeutic role of anti-androgens in the prevention and progression of UBC are critically reviewed. There is now significant evidence in literature to suggest the possible role of sex steroid hormone receptor-mediated signals in the genesis and progression of UBC. These receptors include androgen receptors, estrogen receptors, progesterone receptors, and various other orphan receptors. Excessive or reduced expression of these receptors, as well as alterations in their upstream or downstream pathways, correlate well with the clinical and therapeutic outcomes of UBC.

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Receipt of 5-Alpha Reductase Inhibitors Before Radical Cystectomy: Do They Render High-Grade Bladder Tumors Less Aggressive?

Cited by 11 publications

References 24 publications

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

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

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

Clinical and therapeutic implications of sex steroid hormone receptor status in urothelial bladder cancer

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