Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer,Prostate Cancer and Prostatic Diseases

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Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer
Prostate Cancer and Prostatic Diseases ( IF 5.1 ) Pub Date : 2020-03-09 , DOI: 10.1038/s41391-020-0218-2
A Finelli ₁ , M Komisarenko ₁ , L J Martin ₁ , N Timilshina ₂ , K Jain ₁ , J Morris ₁ , A Zlotta ₂ , G Kulkarni ₁ , N Perlis ₁ , T van der Kwast ₁ , A Evans ₁ , S Ghai ₁ , N Fleshner ₁ , S M H Alibhai ₃ , R J Hamilton ₁

Affiliation

Background

Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS.

Materials/subjects and methods

The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995–2016). Pathologic, grade, and volume progression were the primary end points. Kaplan–Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time.

Results

The cohort included 288 men with median follow-up of 82 months (interquartile range: 37–120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p < 0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p < 0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR: 2.65; CI: 1.65–4.24), grade progression (HR: 2.75; CI: 1.49–5.06), and volume progression (HR: 3.15; CI: 1.78–5.56). The frequency of progression to high-grade (Grade Group 4–5) tumors was not significantly different between the groups.

Conclusions

Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4–5 disease.

中文翻译：

长期使用 5-α-还原酶抑制剂对积极监测前列腺癌的男性是安全有效的

背景

尽管 5-α-还原酶抑制剂 (5ARIs) 已被证明对主动监测 (AS) 的前列腺癌 (PCa) 男性有益，但其长期安全性仍存在争议。我们的目标是描述 5ARI 的使用与 AS 男性 PCa 进展的长期关联。

材料/主题和方法

低风险 PCa 男性队列来自玛格丽特公主 (1995-2016) 前瞻性维护的 AS 数据库。病理学、分级和体积进展是主要终点。进行了 Kaplan-Meier 事件时间分析，并使用 Cox 比例风险回归来确定进展的预测因子，其中 5ARI 暴露作为时间相关变量进行分析。在任何进展事件之前脱离 AS 的患者在当时被审查。

结果

该队列包括 288 名男性，中位随访时间为 82 个月（四分位距：37-120 个月）。在非 5ARI 用户中（n = 203）；114 名男性 (56.2%) 经历了病理进展，而 5ARI 组中的 24 名男性 (28.2%) ( n = 85)，( p < 0.001)。与 5ARI 组相比，非 5ARI 组的等级和体积进展更高（分别为n = 82；40.4% 与n = 19；22.4%，等级进展p = 0.003；n = 87；43.1% 和n = 15; 17.7%，分别为体积级数p < 0.001)。不使用 5ARI 与病理进展（HR：2.65；CI：1.65–4.24）、等级进展（HR：2.75；CI：1.49–5.06）和容量进展（HR：3.15；CI：1.78–5.56）呈独立正相关）。组间进展为高级别（4-5 级）肿瘤的频率没有显着差异。