James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Medicinal Institutions, Baltimore, MD, USA.
BJU Int. 2012 Sep;110(5):651-7. doi: 10.1111/j.1464-410X.2011.10875.x. Epub 2012 Jan 30.
What's known on the subject? and What does the study add? Finasteride (Proscar) and dutasteride (Avodart) are 5-α reductase inhibitors (5-ARIs) used to treat LUTS in men with benign prostatic enlargement. Because these drugs suppress androgens, the theory has been put forward that 5-ARIs might prevent the development of prostate cancer. Careful analysis of two randomized controlled trials, however, showed that, in the clinical setting, this was not the case, and that these drugs can increase the occurrence of more aggressive high-grade disease. Because of this, the U.S. Food and Drug Administration did not approve 5-ARIs for the primary prevention of prostate cancer and notified healthcare professionals about a change in the 'Warnings and Precautions' for these drugs. Interest remains among some for using 5-ARIs in men diagnosed with very low-risk prostate cancer to delay the progression from clinically indolent disease to clinically significant disease requiring treatment. The present study investigated whether 5-ARI use among men with very low-risk prostate cancer in an active surveillance (AS) programme would reduce the number of cancers reclassified to clinically significant disease on surveillance biopsy. Our results do not support the use of 5-ARIs for slowing or preventing cancer progression in men with low-risk prostate cancer, but do suggest that men with very low-risk prostate cancer who take 5-ARIs for LUTS are unlikely to be at increased risk for the development of high grade disease during AS.
To determine whether 5-α reductase inhibitor (5-ARI) use delays cancer reclassification in an active surveillance (AS) cohort.
We performed a retrospective study of 587 men enrolled in an AS programme, who had no history of 5-ARI use. Chi-squared and t-tests were used to compare characteristics of 5-ARI users and non-users. Univariable and multivariable proportional hazards models, treating 5-ARI use as a time-dependent covariate, were used to evaluate the influence of 5-ARIs on the risk of a subsequent biopsy no longer meeting criteria for continued AS (i.e. reclassification).
5-ARI use was initiated in 47 men while on AS. Men using 5-ARIs had larger prostates and higher PSA levels at diagnosis. During 5-ARI use, PSA levels and prostate volume deceased by mean values of 47% and 11%, respectively. Men using 5-ARIs had a mean of 2.5 surveillance biopsies while on the drug. Reclassification occurred in 17% of 5-ARI users compared with 31% of non-users (P = 0.04). Multivariable models (adjusting for age, α-blocker use, PSA level, %free PSA, PSA density, prostate volume and number/percent biopsy core involvement at diagnosis) showed nonsignificant risk reductions for reclassification in 5-ARI users as determined by either tumour extent (hazard ratio [HR] = 0.37 (95% confidence interval [CI] 0.12 to 1.13), P = 0.08) or grade (HR = 0.8 (95% CI 0.25-2.59), P = 0.7).
Treatment with 5-ARIs did not significantly alter the outcome of biopsy reclassification by grade in men with very low-risk prostate cancer.
非那雄胺（保列治）和度他雄胺（可多华）是用于治疗良性前列腺增生症患者下尿路症状的 5-α 还原酶抑制剂（5-ARI）。因为这些药物抑制雄激素，所以有人提出 5-ARI 可能预防前列腺癌的发生。然而，对两项随机对照试验的仔细分析表明，在临床环境中并非如此，这些药物会增加更具侵袭性的高级别疾病的发生。因此，美国食品和药物管理局未批准 5-ARI 用于前列腺癌的一级预防，并就这些药物的“警告和注意事项”向医疗保健专业人员发出通知。一些人仍然对使用 5-ARI 治疗诊断为极低危前列腺癌的男性以延迟从临床惰性疾病到需要治疗的临床显著疾病的进展感兴趣。本研究调查了在主动监测（AS）计划中使用 5-ARI 是否会减少临床上意义不大的疾病的癌症重新分类。我们的结果不支持使用 5-ARI 来减缓或预防低危前列腺癌患者的癌症进展，但确实表明患有极低危前列腺癌且因下尿路症状而服用 5-ARI 的男性在 AS 期间不太可能因使用 5-ARI 而增加发生高级别疾病的风险。
确定 5-α 还原酶抑制剂（5-ARI）的使用是否会延迟主动监测（AS）队列中的癌症重新分类。
我们对 587 名未使用过 5-ARI 的参加 AS 计划的男性进行了回顾性研究。使用卡方检验和 t 检验比较了 5-ARI 使用者和非使用者的特征。使用单变量和多变量比例风险模型，将 5-ARI 使用视为时间依赖性协变量，评估 5-ARI 对随后活检不再符合继续 AS 标准（即重新分类）的风险的影响。
在 AS 期间，有 47 名男性开始使用 5-ARI。使用 5-ARI 的男性前列腺更大，诊断时 PSA 水平更高。在使用 5-ARI 期间，PSA 水平和前列腺体积分别平均下降了 47%和 11%。使用 5-ARI 的男性平均进行了 2.5 次监测活检。与非使用者（31%）相比，17%的 5-ARI 使用者发生重新分类（P = 0.04）。多变量模型（调整年龄、α 受体阻滞剂使用、PSA 水平、%游离 PSA、PSA 密度、前列腺体积和诊断时活检核心受累的数量/百分比）显示，5-ARI 使用者的肿瘤范围（危险比 [HR] = 0.37（95%置信区间 [CI] 0.12 至 1.13），P = 0.08）或分级（HR = 0.8（95%CI 0.25-2.59），P = 0.7）风险降低无统计学意义。
在极低危前列腺癌患者中，5-ARI 治疗并未显著改变活检分级重新分类的结果。
