Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre, Department of Clinical Pharmacology, Rennes University Hospital, Rennes, France.
University of Rennes, EA 7449 REPERES 'Pharmacoepidemiology and Health Services Research', Rennes, France.
BJU Int. 2019 Feb;123(2):293-299. doi: 10.1111/bju.14495. Epub 2018 Sep 11.
To assess the association between 5α-reductase inhibitor (5-ARI) use and high grade (Gleason score 8-10) prostate cancer.
We conducted a population-based nested matched case-control study using the French national health insurance database linked to data from all pathology laboratories in Brittany, France. Among 74 596 patients with ≥1 drug reimbursement for symptomatic benign prostate hypertrophy (BPH) between 1 January 2010 and 31 December 2011, 767 incident prostate cancer cases between 1 January 2012 and 31 December 2013 were matched according to age and delay between the first observed delivery of drug for BPH (5-ARIs, α-blockers or phytotherapy) and diagnostic date of the case to five control patients, using an incidence density sampling design.
A total of 963 patients (153 cases, 810 controls) had been exposed to 5-ARIs. A significant heterogeneity (P = 0.005) was detected across cancer grades when estimating the association between prostate cancer and long-term (≥2 years) 5-ARI use vs no 5-ARI exposure: adjusted conditional odds ratio 1.76 (95% confidence interval [CI] 0.97-3.21) for Gleason score ≥8 and 0.64 (95% CI 0.44-0.93) for Gleason score < 8.
Our results indicate an increased risk of high grade and a decreased risk of low grade prostate cancer associated with 5-ARI use. Patients treated for >2 years with 5-ARIs should be informed about the increased risk of development of high grade disease.
评估 5α-还原酶抑制剂（5-ARI）的使用与高级别（Gleason 评分 8-10）前列腺癌之间的关联。
我们进行了一项基于人群的嵌套病例对照研究，使用法国国家健康保险数据库与法国布列塔尼所有病理实验室的数据进行了关联。在 2010 年 1 月 1 日至 2011 年 12 月 31 日期间，有 74596 名患者至少有 1 种药物用于治疗症状性良性前列腺增生症（BPH），2012 年 1 月 1 日至 2013 年 12 月 31 日期间，767 例前列腺癌病例与年龄和 BPH（5-ARI、α受体阻滞剂或植物疗法）首次观察到的药物治疗到病例诊断日期之间的延迟相匹配，使用发病率密度抽样设计匹配了 5 名对照患者。
共有 963 名患者（153 例病例，810 例对照）接受了 5-ARI 治疗。当估计前列腺癌与长期（≥2 年）5-ARI 使用与无 5-ARI 暴露之间的关联时，不同癌症分级之间存在显著的异质性（P = 0.005）：Gleason 评分≥8 的调整后的条件优势比为 1.76（95%置信区间 [CI]，0.97-3.21），Gleason 评分<8 的调整后的条件优势比为 0.64（95% CI，0.44-0.93）。
我们的结果表明，5-ARI 的使用与高级别前列腺癌的风险增加和低级别前列腺癌的风险降低相关。接受 5-ARI 治疗超过 2 年的患者应被告知发生高级别疾病的风险增加。
