Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
JAMA Netw Open. 2024 Aug 1;7(8):e2430223. doi: 10.1001/jamanetworkopen.2024.30223.
5-alpha-reductase-inhibitors (5-ARIs) are approved for treating benign prostatic hyperplasia (BPH) and have been found to reduce prostate cancer (PCa) risk by 25%. However, trials also have shown 5-ARIs to be associated with high-grade PCa. Whether 5-ARIs increase mortality among those with a diagnosis of PCa remains unclear.
To determine long-term outcomes of clinically localized PCa arising in individuals taking 5-ARIs compared with nonusers.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted between January 2003 and October 2017. Eligible participants were men aged 65 years or older in Ontario, Canada, who developed clinically localized PCa with complete pathological abstraction from the Ontario Health Administrative Databases. Data analysis occurred from November 2017 to November 2022.
5-ARIs before PCa diagnosis.
The primary outcomes were overall mortality and PCa-specific mortality. Cause-specific hazard models with inverse probability treatment weights (IPTW) were used to examine associations of 5-ARI use with mortality outcomes. Sensitivity analyses based on prediagnostic 5-ARI use, Gleason score, comorbidity, 5-ARI indication, prostate-specific antigen modeling, and statin use were also performed.
The cohort included 19 938 patients with PCa. Of these, 2112 (10.6%; median [IQR] age, 74 [70-79] years) were 5-ARI users and 17 826 (89.4%; median [IQR] age, 71 [68-76] years) were nonusers. During a median (IQR) follow-up of 8.96 (6.28-12.17) years, 6053 (30.4%) died, including 1047 (5.3%) from PCa. 5-ARI use appeared to be associated with increased overall and PCa specific mortality in crude analyses; however, after IPTW, 5-ARI use was not associated with overall mortality (hazard ratio, 0.98; 95% CI, 0.90-1.07; P = .77) or PCa-specific mortality (hazard ratio, 1.02; 95% CI, 0.83-1.25; P = .84).
In this population-based cohort study of 5-ARI use prior to PCa diagnosis including long-term follow-up and clinicopathologic details, prediagnostic 5-ARI use was not associated with PCa-specific or all-cause mortality. This study offers reassuring safety data for patients using 5-ARIs before PCa diagnosis for both BPH and chemopreventive reasons.
5-α还原酶抑制剂（5-ARIs）被批准用于治疗良性前列腺增生（BPH），并已被发现可将前列腺癌（PCa）风险降低 25%。然而，临床试验还表明 5-ARIs 与高级别 PCa 有关。5-ARIs 是否会增加确诊为 PCa 患者的死亡率仍不清楚。
确定使用 5-ARIs 与未使用者相比，在患有临床局限性前列腺癌的个体中产生的长期结局。
设计、设置和参与者：这是一项基于人群的队列研究，于 2003 年 1 月至 2017 年 10 月进行。合格的参与者是在加拿大安大略省年龄在 65 岁或以上的人群，他们在安大略省健康行政数据库中患有完整的病理摘要的临床局限性前列腺癌。数据分析于 2017 年 11 月至 2022 年 11 月进行。
5-ARI 在 PCa 诊断前使用。
主要结局是总死亡率和 PCa 特异性死亡率。使用逆概率治疗加权（IPTW）的特定原因危害模型来检查 5-ARI 使用与死亡率结局的关联。还进行了基于诊断前 5-ARI 使用、Gleason 评分、合并症、5-ARI 指征、前列腺特异性抗原建模和他汀类药物使用的敏感性分析。
该队列包括 19938 名患有 PCa 的患者。其中，2112 名（10.6%；中位[IQR]年龄，74[70-79]岁）为 5-ARI 用户，17826 名（89.4%；中位[IQR]年龄，71[68-76]岁）为非使用者。在中位（IQR）随访 8.96（6.28-12.17）年期间，有 6053 人（30.4%）死亡，其中 1047 人（5.3%）死于 PCa。在初步分析中，5-ARI 使用似乎与总死亡率和 PCa 特异性死亡率增加有关；然而，在 IPTW 后，5-ARI 使用与总死亡率（危害比，0.98；95%CI，0.90-1.07；P=0.77）或 PCa 特异性死亡率（危害比，1.02；95%CI，0.83-1.25；P=0.84）无关。
在这项包括长期随访和临床病理细节的基于人群的队列研究中，5-ARI 在 PCa 诊断前的使用与 PCa 特异性或全因死亡率无关。这项研究为因 BPH 和化学预防原因在 PCa 诊断前使用 5-ARIs 的患者提供了令人安心的安全性数据。
