Department of Urology, Ryhov Hospital, Jonkoping, Sweden.
Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden.
J Urol. 2020 Oct;204(4):714-719. doi: 10.1097/JU.0000000000001038. Epub 2020 Apr 3.
5α-Reductase inhibitors reduced the risk of prostate cancer in 25% in 2 randomized trials but increased the risk of Gleason 8-10 at biopsy. One explanation is that 5α-reductase inhibitors induce morphological changes in prostate cancer cells similar to higher Gleason grades but without its adverse biology. We compared risk of prostate cancer death between men on 5α-reductase inhibitors and men not on 5α-reductase inhibitors before prostate cancer diagnosis in each Gleason Grade Group.
Prostate Cancer data Base Sweden consists of linkages between the National Prostate Cancer Register, the Prescribed Drug Registry and the Cause of Death Registry. Of 89,227 men diagnosed with prostate cancer between July 2007 and December 2016, 5,816 had been on 5α-reductase inhibitors for more than 180 days before the date of diagnosis. Followup ended in December 2018. A Cox proportional hazard model was used to assess hazard ratio for prostate cancer death. Adjustments for age, comorbidity, education and curative treatment were made. Men with high risk cancer were stratified according to Gleason Grade Group.
In men with high risk cancer the risk of prostate cancer death was similar among 5α-reductase inhibitor users and nonusers, with Gleason Grade Group 1 HR 1.02 (95% CI 0.53-1.95), Gleason Grade Group 2 HR 1.04 (95% CI 0.65-1.69), Gleason Grade Group 3 HR 1.27 (95% CI 0.89-1.80), Gleason Grade Group 4 HR 0.95 (95% CI 0.76-1.18) and Gleason Grade Group 5 HR 0.99 (95% CI 0.83-1.19), for 5α-reductase inhibitor users vs nonusers.
We found no evidence that 5α-reductase inhibitors affect Gleason grading as no difference in mortality was observed among 5α-reductase inhibitor users and nonusers in each Gleason group.
5α-还原酶抑制剂在两项随机试验中降低了 25%的前列腺癌风险，但增加了活检时 Gleason 8-10 的风险。一种解释是 5α-还原酶抑制剂诱导前列腺癌细胞发生形态变化，类似于更高的 Gleason 分级，但没有其不良生物学特性。我们比较了在每个 Gleason 分级组中，在前列腺癌诊断前使用 5α-还原酶抑制剂的男性和未使用 5α-还原酶抑制剂的男性之间前列腺癌死亡的风险。
瑞典前列腺癌数据库由国家前列腺癌登记处、处方药物登记处和死因登记处之间的链接组成。在 2007 年 7 月至 2016 年 12 月期间诊断为前列腺癌的 89227 名男性中，有 5816 名男性在诊断日期前使用 5α-还原酶抑制剂超过 180 天。随访于 2018 年 12 月结束。使用 Cox 比例风险模型评估前列腺癌死亡的危险比。调整了年龄、合并症、教育程度和治疗方法。根据 Gleason 分级组对高危癌症患者进行分层。
在高危癌症患者中，使用 5α-还原酶抑制剂的患者与未使用者的前列腺癌死亡风险相似，Gleason 分级组 1 的 HR 为 1.02（95%CI 0.53-1.95），Gleason 分级组 2 的 HR 为 1.04（95%CI 0.65-1.69），Gleason 分级组 3 的 HR 为 1.27（95%CI 0.89-1.80），Gleason 分级组 4 的 HR 为 0.95（95%CI 0.76-1.18），Gleason 分级组 5 的 HR 为 0.99（95%CI 0.83-1.19），使用 5α-还原酶抑制剂的患者与未使用者。
我们没有发现 5α-还原酶抑制剂影响 Gleason 分级的证据，因为在每个 Gleason 组中，使用和未使用 5α-还原酶抑制剂的患者之间的死亡率没有差异。
