5-alpha-reductase inhibitors for prostate cancer prevention

 

Abstract

Background

Five-alpha-reductase inhibitors (5ARI) are frequently used to treat bothersome lower urinary tract symptoms associated with benign prostatic hyperplasia and male androgenic alopecia. They have potential as chemopreventive agents.

Objectives

We sought to estimate the effectiveness and harms of 5ARI in preventing prostate cancer.

Search methods

MEDLINE, PreMEDLINE, and the Cochrane Collaboration Library were searched through April 2007 to identify randomized trials.

Selection criteria

For prostate cancer outcomes we included randomized controlled trials of at least 1 year in duration published after 1984. For non-prostate cancer outcomes, randomized trials were included if: they were at least 6 months in duration published after 1999.

Data collection and analysis

The primary outcome was prostate cancer period-prevalence "for-cause." "For-cause" was defined as prostate cancer clinically detected based on symptoms, an abnormal digital rectal exam, or detected as a result of an abnormal prostate specific antigen value. Trials were categorized as long (> 2 year), mid (1 to 2 years) and short (< 1 year) term.

Main results

Nine trials reported prostate cancer period-prevalence. Three trials using finasteride lasted four years or longer but only one (the Prostate Cancer Prevention Trial) was specifically designed to assess the impact of 5ARI on prostate cancer period-prevalence. The mean age of enrollees was 64.6 years, 91% were white, mean PSA was 2.1 ng/mL. For-cause prostate cancers comprised 54% of all cancers detected. Finasteride was associated with a 26% relative risk reduction in prostate cancers detected for-cause among all randomized subjects (relative risk 0.74 (95% CI 0.67 to 0.83); absolute risk reduction = 1.4% (3.5% versus 4.9%). Six trials assessed prostate cancers detected overall with a pooled 26% relative reduction favoring 5ARI (relative risk 0.74 (95% CI 0.55 to1.00); 2.9% absolute reduction (6.3% versus 9.2%). Reductions were observed regardless of age, race or family history of prostate cancer but not among men with baseline PSA > 4.0 ng/mL. A greater number of high Gleason score tumors (7 to 10 or 8 to 10) occurred in men on finasteride in the PCPT. Impaired sexual or erectile function or endocrine effects were more common with finasteride than placebo.

Authors' conclusions

Five-alpha-reductase inhibitors reduce prostate cancer risk but may increase the risk of high-grade disease in men who are undergoing regular screening for prostate cancer using prostate specific antigen and digital rectal examination. Effects are consistent across race, family history and age and possibly 5ARI but were limited to men with baseline PSA values < 4.0 ng/mL. The impact of 5ARI on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear. Information is inadequate to assess the impact of 5ARI on mortality.

 

Plain language summary

Five-alpha-reductase inhibitor drugs, such as finasteride or dutasteride, reduce the risk prostate cancer in men who have routine prostate cancer screening

Five-alpha-reductase inhibitor drugs have potential as chemopreventive agents. Reduction of prostate cancer was similar between racial groups, age groups (aged 65 years or older compared to younger age groups) and those with or without a family history of prostate cancer. Reduction of prostate cancer was limited to men who had a baseline prostate specific antigen (PSA) values less than 4.0 ng/mL. However, use of five-alpha-reductase inhibitors may also increase the risk of high-grade prostate cancer in men undergoing prostate cancer screening. Future research is needed to determine if the use of five-alpha-reductase inhibitors can reduce prostate cancer in men who are not being regularly screened for prostate cancer. Future studies should also determine whether five-alpha-reductase inhibitors can reduce death and prostate cancer death and further evaluate the risk of developing high-grade prostate cancer.

 

摘要

背景

5α還原酉每抑制劑對前列腺癌的預防

5α還原酉每抑制劑 (5ARI) 常用來治療和惱人的前列腺肥大相關的下泌尿道症狀以及雄性禿，可望成為化學預防性藥物。

目標

我們評估5ARI在前列腺癌預防上之效用和毒性。

搜尋策略

使用MEDLINE，PreMEDLINE，和the Cochrane Collaboration搜尋2007年4月至今的隨機對照臨床試驗。

選擇標準

針對前列腺癌的預後指標，我們收集於1984年之後發表，至少進行一年的隨機對照試驗。對於非前列腺癌的預後指標，則是收集1999年以後出版，至少進行6個月的隨機對照臨床試驗。

資料收集與分析

主要評估結果為前列腺癌某一時期，因各種原因 (forcause) 而診斷之前列腺癌盛行率。「原因」意指因有臨床症狀，肛門指診異常或前列腺特異抗原 (prostate specific antigen) 值不正常，而被診斷出患有前列腺癌。試驗分為長期 (> 2年)，中期 (1−2年) 和短期 (<1年) 試驗。

主要結論

共有9項臨床試驗列出前列腺癌研究期間盛行率 (periodprevalence)。共有3項臨床試驗使用finasteride，歷時四年以上，而只有一項 (the Prostate Cancer Prevention Trial (PCPT)) 是特別設計用來評估5ARI對前列腺癌之periodprevalence。平均參與受試者年齡64.6歲，91%為白人，平均PSA值2.1 ng / ml。Forcause前列腺癌佔所有癌症比例54%。所有隨機分組之受試者中，Finasteride使forcause診斷出的前列腺癌風險下降26% (相對風險0.74 [95% CI 0.67−0.83]。絕對風險減少1.4% (3.5% v.s. 4.9%)。6項評估前列腺癌的隨機試驗，顯示5ARI合併減少了26%之相對風險 (相對風險0.74 [95% CI 0.55−1.00]) ；絕對風險減少2.9% (6.3% v.s. 9.2%)。風險減少不受年齡、種族、或家族病史所影響，但不包含受試前PSA> 4.0 ng/ml的男子。在PCPT試驗，使用finasteride的男性有較高惡性腫瘤 (Gleason score 7−10或8−10) 的機會，finasteride組中，性功能、勃起障礙或是內分泌影響也比安慰劑組較多。

作者結論

對於定期接受前列腺特異抗原檢測及肛門指診篩檢的男性，5ARI可減少前列腺癌機率，但也會增加罹患較高惡性度癌的風險。這種效果僅限於受試前PSA< 4.0 ng/ml之男性，且不受種族、家族病史、年齡甚或不同的5ARI等因素影響。對於未接受定期篩檢之男性，5ARI對於罹患前列腺癌相對或絕對風險的影響不明。缺乏足夠資料評估5ARI對死亡率的影響。

翻譯人

本摘要由臺灣大學附設醫院王禎薇翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

5ARI，如finasteride或dutasteride，能降低定期接受前列腺癌篩檢之男性罹患前列腺癌之風險。5ARI有可能成為化學預防劑。在不同種族、年齡組 (年齡65歲或以上和較年輕組) 以及家族病史族群中，前列腺癌減少比率相似。只有PSA基準值小於4.0 ng / ml之男性觀察到前列腺癌比率減少。不過定期接受篩檢的男性，使用5ARI也可能增加罹患高惡性度前列腺癌的風險。欲確定是否使用5ARI，可以降低未定期接受前列腺癌篩選之男性罹患前列腺癌的機率，還需更多的研究。以後的研究也須確認是否5ARI能夠降低前列腺癌死亡率，並評估罹患高惡性度前列腺癌的風險。