University of Tampere, Faculty of Medicine and Health Technology, Tampere, Finland.
Department of Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Prostate. 2019 May;79(6):583-591. doi: 10.1002/pros.23768. Epub 2019 Jan 16.
Improved prostate cancer (PCa) survival by statin use has been reported among PCa patients managed with radiation or androgen deprivation therapy (ADT), while results are controversial for men managed surgically. We evaluate the association between cholesterol-lowering medication with initiation of ADT and disease-specific death among PCa cases who underwent radical prostatectomy in Finland between 1995 and 2013.
The study cohort included 14 424 men with PCa who underwent radical prostatectomy in Finland between 1995 and 2013. Cases were identified from national hospital discharge registry. Clinical data were amended from patient files of the treating hospitals. Information on co-morbidities, additional radiation- or chemotherapy, and causes of deaths were collected from national registries. Personal-level data on medication use during 1995-2014 were gathered from national prescription database. Registry linkages were carried out using personal identification number. Lipid-lowering drugs were categorized into statins and non-statin drugs. Risk of PCa death and initiation of ADT was analyzed using Cox-regression model with adjustment for age, radiation therapy, chemotherapy, co-morbidities and other drug use. Statin use was analyzed as time-dependent variable. Delayed risk associations were evaluated in lag-time analysis.
Compared to non-users the risk of PCa death was significantly lower among statin users before PCa diagnosis (HR 0.70, 95%CIs 0.52-0.95). For statin use after PCa diagnosis the risk was lowered in age-adjusted analysis (HR 0.76 95%CIs 0.62-0.93) but not after multivariable-adjustment. Post-diagnostic statin use was associated with improved PCa-specific survival in 1, 3 and 5 years lag-time analyses. The risk reduction was clearest for statin use initiated 5 years earlier (HR 0.71 95%CIs 0.55-0.92). Use of statins both before and after PCa diagnosis was associated with reduced risk of ADT use (HR 0.72 95%CIs 0.65-0.80 and HR 0.73, 95%CI 0.67-0.80, respectively). The risk of ADT decreased by increasing intensity of statin use before diagnosis.
Statin use among surgically treated PCa patients has significant association with decreased risk of starting ADT and PCa death. The risk is lowered especially among men with statin use before PCa diagnosis and in men who used statins at high-dose. Our results are hypothesis generating due to retrospective study design.
在接受放疗或雄激素剥夺治疗（ADT）的前列腺癌（PCa）患者中，使用他汀类药物已被报道能提高 PCa 患者的生存率，而对于接受手术治疗的男性，结果则存在争议。我们评估了芬兰在 1995 年至 2013 年间接受根治性前列腺切除术的 PCa 患者中，使用降脂药物与 ADT 起始之间与疾病特异性死亡之间的关联。
研究队列包括 1995 年至 2013 年间在芬兰接受根治性前列腺切除术的 14424 名 PCa 患者。病例从国家住院出院登记处确定。临床数据从治疗医院的患者档案中修改。从国家登记处收集合并症、附加放疗或化疗以及死亡原因的信息。1995 年至 2014 年期间使用药物的数据从国家处方数据库中收集。使用个人身份证号进行登记链接。将降脂药物分为他汀类药物和非他汀类药物。使用 Cox 回归模型分析 PCa 死亡风险和 ADT 的起始，调整年龄、放疗、化疗、合并症和其他药物使用。他汀类药物的使用作为时间依赖性变量进行分析。在滞后时间分析中评估延迟的风险关联。
与非使用者相比，在 PCa 诊断前使用他汀类药物的患者 PCa 死亡风险显著降低（HR 0.70，95%CI 0.52-0.95）。在调整年龄后的分析中，PCa 诊断后使用他汀类药物的风险降低（HR 0.76，95%CI 0.62-0.93），但在多变量调整后则没有。在 1、3 和 5 年的滞后时间分析中，诊断后使用他汀类药物与改善 PCa 特异性生存相关。他汀类药物起始时间越早，风险降低越明显（HR 0.71，95%CI 0.55-0.92）。在 PCa 诊断前后使用他汀类药物与 ADT 使用风险降低相关（HR 0.72，95%CI 0.65-0.80 和 HR 0.73，95%CI 0.67-0.80）。在诊断前，他汀类药物使用强度越高，ADT 使用风险越低。
在接受手术治疗的 PCa 患者中，使用他汀类药物与降低开始 ADT 和 PCa 死亡的风险显著相关。在 PCa 诊断前使用他汀类药物的男性和高剂量使用他汀类药物的男性中，风险降低尤其明显。由于采用回顾性研究设计，我们的结果仅是提出假设。
