Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland.
Tays Cancer Centre, Department of Urology, Tampere, Finland.
JAMA Oncol. 2022 Jan 1;8(1):61-68. doi: 10.1001/jamaoncol.2021.5672.
Prostate-specific antigen (PSA) screening for prostate cancer has resulted in a slight reduction in prostate cancer mortality but also a concomitant overdiagnosis of low-risk tumors. Prostate-specific antigen levels are affected by use of cholesterol-lowering statin drugs, but the association of statin use with PSA screening performance is unknown.
To investigate whether statin use was associated with outcomes of a randomized PSA-based prostate cancer screening intervention.
DESIGN, SETTING, AND PARTICIPANTS: This post hoc subgroup analysis of a cohort from a population-based randomized clinical trial used data from the population-based Finnish Randomized Study of Prostate Cancer Screening, which randomized men to PSA screening or routine care from March 1, 1996, to December 31, 1999, with follow-up continuing until December 31, 2015. The population included all men aged 55 to 67 years at baseline and residing in the Tampere or Helsinki districts of Finland. Information on statin purchases from 1996 to 2009 was obtained from a national prescription registry. Eligible men were identified from the population registry of Finland. Prevalent prostate cancer cases at baseline were excluded. Data were analyzed from January 1, 2019 to March 31, 2021.
Three invitations for PSA screening at 4-year intervals from 1996 to 2007 vs routine care.
Risk for prostate cancer overall, high-risk disease, and prostate cancer mortality in the screening group vs the control group as an intention-to-treat analysis. The analysis was stratified by statin use.
The study comprised 78 606 men (median age, 59 years [range, 55-67 years]) with statin purchase data available. Although PSA screening was associated with increased prostate cancer incidence among statin nonusers (screening vs control, 11.2 vs 8.6 per 1000 person-years); rate ratio [RR], 1.31; 95% CI, 1.24-1.38), no similar increase in incidence was observed among statin users (6.9 vs 5.9 per 1000 person-years; RR, 1.02; 95% CI, 0.95-1.10; P < .001 for interaction). Incidence of low-risk (Gleason score 6) and localized tumors was lower among statin users, whereas detection of tumors with a Gleason score of 8 to 10 was similar. Screening was associated with a lower incidence of metastatic tumors regardless of statin use.
In this post hoc subgroup analysis of a cohort from a population-based randomized clinical trial, PSA screening among statin users was associated with a decreased incidence of advanced prostate cancer that was similar among statin nonusers, but with less increase in detection of low-grade localized tumors in statin users than in nonusers. These findings suggest that statin use does not materially compromise benefits of PSA-based screening.
前列腺特异性抗原（PSA）筛查用于前列腺癌，虽然降低了前列腺癌死亡率，但也导致了低危肿瘤的过度诊断。PSA 水平受降胆固醇他汀类药物的影响，但他汀类药物的使用与 PSA 筛查结果的关联尚不清楚。
调查他汀类药物的使用是否与基于 PSA 的前列腺癌筛查干预的结果相关。
设计、地点和参与者：这是一项基于人群的随机临床试验队列的事后亚组分析，该研究使用了基于人群的芬兰前列腺癌筛查随机研究的数据，该研究于 1996 年 3 月 1 日至 1999 年 12 月 31 日随机分配男性接受 PSA 筛查或常规护理，随访持续至 2015 年 12 月 31 日。该人群包括基线时年龄在 55 至 67 岁之间且居住在芬兰坦佩雷或赫尔辛基地区的所有男性。1996 年至 2009 年他汀类药物购买信息来自国家处方登记处。从芬兰的人口登记处确定合格的男性。排除基线时患有前列腺癌的患者。数据分析于 2019 年 1 月 1 日至 2021 年 3 月 31 日进行。
每隔 4 年从 1996 年到 2007 年进行三次 PSA 筛查邀请，与常规护理相比。
筛查组与对照组作为意向治疗分析的前列腺癌总体、高危疾病和前列腺癌死亡率的风险。该分析按他汀类药物的使用情况进行分层。
研究纳入了 78606 名男性（中位年龄 59 岁[范围，55-67 岁]），有他汀类药物购买数据。尽管 PSA 筛查与非他汀类药物使用者的前列腺癌发病率增加有关（筛查组与对照组相比，每 1000 人年分别为 11.2 例和 8.6 例；RR，1.31；95%CI，1.24-1.38），但在他汀类药物使用者中未观察到类似的发病率增加（每 1000 人年分别为 6.9 例和 5.9 例；RR，1.02；95%CI，0.95-1.10；P<0.001 用于交互作用）。他汀类药物使用者的低危（Gleason 评分 6）和局限性肿瘤的发病率较低，而 Gleason 评分 8 至 10 的肿瘤的检出率相似。无论是否使用他汀类药物，筛查均与转移性肿瘤的发病率降低有关。
在这项基于人群的随机临床试验队列的事后亚组分析中，他汀类药物使用者的 PSA 筛查与进展期前列腺癌发病率降低有关，与非他汀类药物使用者相似，但与他汀类药物使用者中低级别局限性肿瘤的检出率增加相比，非他汀类药物使用者的发病率增加较少。这些发现表明，他汀类药物的使用不会对基于 PSA 的筛查的获益产生实质性影响。
