Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
Department of Clinical Sciences at Danderyd Hospital, Danderyd, Sweden.
JAMA Oncol. 2022 Jul 1;8(7):1019-1026. doi: 10.1001/jamaoncol.2022.1501.
There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM).
To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021.
After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190).
Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM.
The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively).
The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.
有证据表明，5α-还原酶抑制剂（5-ARI）是治疗良性前列腺增生的标准药物，与前列腺癌（PCa）发病率的降低有关。然而，迄今为止，关于与前列腺癌死亡率（PCM）的关联的研究结果存在矛盾。
评估 5-ARI 治疗与无前列腺癌病史男性 PCM 的相关性。
设计、地点和参与者：这项基于人群的队列研究于 2007 年 1 月 1 日至 2018 年 12 月 31 日在瑞典斯德哥尔摩进行，包括研究期间进行前列腺特异性抗原（PSA）检测的 429977 名男性。研究的起始时间为首次 PSA 检测后 1 年。数据于 2021 年 9 月至 2021 年 12 月进行分析。
在首次 PSA 检测后，有 2 次或更多新开具的 5-ARI、非那雄胺或度他雄胺处方的男性被认为是 5-ARI 用户（n=26190）。
主要结局为 PCM。使用 Cox 比例风险回归模型计算了所有原因死亡率和 PCM 的多变量调整后的风险比（HR）和 95%置信区间。
研究队列包括 349152 名男性。接受 2 次或更多次 5-ARI 处方的患者中位（IQR）年龄为 66（61-73）岁，未接受 5-ARI 处方的患者中位（IQR）年龄为 57（50-64）岁。中位随访时间为 8.2（IQR，4.9-10）年，未暴露组有 2257619 人年，暴露组有 124008 人年。5-ARI 治疗的中位暴露时间为 4.5（IQR，2.1-7.4）年。随访期间，35767 名男性（8.3%）死亡，其中 852 名死于前列腺癌。调整后的多变量生存分析显示，较长暴露时间（0.1-2.0 年：调整 HR，0.89；95%CI，0.64-1.25；>8 年：调整 HR，0.44；95%CI，0.27-0.74）与 PCM 风险降低相关。暴露组与未暴露组之间在所有原因死亡率方面无统计学差异。接受 5-ARI 治疗的男性每年接受 PSA 检测和活检的次数多于未暴露组（中位数分别为 0.63 次比 0.33 次和 0.22 次比 0.12 次）。
这项基于队列的研究结果表明，在一个无前列腺癌病史的大型人群队列中，5-ARI 治疗与 PCM 增加之间没有关联。此外，还观察到与 PCM 风险降低呈时间依赖性关联，5-ARI 治疗时间越长，风险越低。需要进一步研究以确定这些差异是由于药物的内在作用还是前列腺癌检测的差异所致。
