Use of 5α-Reductase Inhibitors for Prostate Cancer Chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline

Johns Hopkins University, Baltimore, Maryland, United States
The Journal of urology (Impact Factor: 4.47). 02/2009; 181(4):1642-57. DOI: 10.1016/j.juro.2009.01.071
Source: PubMed


To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention.
The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention.
The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence.
Asymptomatic men with a prostate-specific antigen (PSA) </=3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

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    • "The FDA decision was based on the PCPT and the REDUCE trials, two large, randomized, placebo-controlled trials. The ASCO and AUA deleted the use of 5-ARIs for prostate cancer chemoprevention from the main "Clinical Guidelines" on the AUA homepage, after the FDA denied a supplemental New Drug Application for dutasteride for prostate cancer chemoprevention (Table 2) [31,32]. "
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    ABSTRACT: The key enzyme in the androgen synthesis and androgen receptor pathways is 5α-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia.
    Korean journal of urology 04/2013; 54(4):213-9. DOI:10.4111/kju.2013.54.4.213
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    • "There is an increasing interest in the use of 5ARIs for PCa chemoprevention. The American Society of Clinical Oncology (ASCO) and American Urological Association Practice Guidelines Committee jointly convened a panel of experts to develop evidence-based recommendations [35]. Although this issue is beyond the scope of this article, some findings may have clinical implications in patients receiving 5ARIs for symptomatic BPH. "
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    ABSTRACT: Benign prostatic hyperplasia (BPH) is a progressive disease that is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. Therefore, the goals of therapy for BPH are not only to improve LUTS in terms of symptoms and urinary flow, but also to identify those patients at a risk of unfavorable disease progression and to optimize their management. This article reviews the current status of therapy with 5alpha-reductase inhibitors (5ARIs), namely fiasteride and dutasteride, for men with LUTS and BPH. Data from key randomized controlled trials (Oxford level 1b) on the use of 5ARIs are analyzed. The efficacy of 5ARIs either as monotherapy or in combination with alpha(1)-adrenoceptor antagonists in the management of LUTS and the impact of monotherapy and combined therapy on BPH progression are discussed. Further promises, including the withdrawal of the alpha-blocker from the combined medical treatment and the potential clinical implications from the use of 5ARIs for prostate cancer chemoprevention in patients receiving 5ARIs for symptomatic BPH are highlighted. Current evidence shows that 5ARIs are effective in treating LUTS and preventing disease progression and represent a recommended option in treatment guidelines for men who have moderate to severe LUTS and enlarged prostates.
    World Journal of Urology 12/2009; 28(1):9-15. DOI:10.1007/s00345-009-0493-y · 2.67 Impact Factor
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    • "All randomized controlled trials published after 1984 of at least 1 year duration were included in the review. Based on this review, the AUA recently released guidelines which address the role of finasteride in prostate cancer prevention.44 Asymptomatic men with PSA ≤ 3.0 ng/mL should be notified that finasteride may reduce the incidence of prostate cancer with an additional discussion of the elevated rate of high-grade cancer with potential explanations for this potential risk. "
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    ABSTRACT: Benign prostatic hyperplasia (BPH) is a complex and progressive disease common in aging men. While associated with bothersome lower urinary tract symptoms, it may also result in additional serious complications such as refractory hematuria, acute urinary retention, and BPH-related surgery. Medical therapy has been offered as an approach to halt this progression and perhaps reverse the pathophysiology of BPH. While alpha-blockers provide rapid relief in the form of improved flow rate, their effects may not reduce the overall risk of BPH-related complications. 5alpha-reductase inhibitors were therefore introduced to affect the underlying disease process by inhibiting the enzyme which converts testosterone to dihydrotesterone, the primary androgen involved in normal and abnormal prostate growth. Through this inhibition, prostate size is decreased, thereby reducing the risk of acute urinary retention and BPH-related surgery while providing symptom control. These effects are most pronounced in men with enlarged prostates (>25 mL) who are at the greatest risk of disease progression. This article reviews the literature for finasteride used in the treatment of BPH and provides evidence for its efficacy, safety and tolerability, applicability for combination therapy, and considerations of its effects on prostate cancer risk.
    Therapeutics and Clinical Risk Management 07/2009; 5(3):535-45. · 1.47 Impact Factor
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