Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA 91101, USA.
BJU Int. 2013 May;111(6):954-62. doi: 10.1111/j.1464-410X.2012.11639.x. Epub 2013 Mar 6.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Statins have shown broad spectrum anti-cancer properties in laboratory studies. In epidemiological studies, use of statins has been associated with reduced risk of advanced prostate cancer. However, the effects of statins on prostate cancer disease progression following curative treatment have not been extensively studied, and previous studies reported conflicting results. This study found no clear association between overall statin use and risk of disease progression, as well as lack of a monotone dose-response relationship between the use of statins, whether it was use before or after prostatectomy, and prostate cancer disease progression.
To investigate whether use of HMG-CoA reductase inhibitors ('statins'), which have shown broad spectrum anti-cancer properties in laboratory studies, is associated with a reduced risk of recurrence in patients with prostate cancer who undergo radical prostatectomy.
All men with incident prostate cancer diagnosed between 2004 and 2005 who subsequently underwent radical prostatectomy by the end of 2005 in the Kaiser Permanente Southern California (KPSC) health plan were identified using KPSC's cancer registry. Subjects were followed for up to 5 years after prostatectomy for (i) biochemical recurrence, defined as a single PSA measurement >0.2 ng/mL, and (ii) clinical disease progression, defined as diagnosis of metastatic disease or prostate-cancer-related death. Information on statin use, demographics, comorbidities, patho-clinical factors and outcomes were ascertained from KPSC's electronic medical records. The effects of statin use prior to and after prostatectomy were both examined using bivariate and multivariate Cox models, adjusting for known prognostic factors. For postoperative statin exposure, a time-dependent Cox model was used.
A total of 1200 men were included; 37% had preoperative and 56% had postoperative statin use. Neither preoperative nor postoperative statin use was associated with biochemical recurrence (hazard ratio [HR] = 1.00 [0.72-1.39] and 1.05 [0.76-1.46], respectively) or clinical disease progression (HR = 0.63 [0.31-1.27] and 1.20 [0.63-2.30], respectively). No clear dose-response relationship was found for duration of use.
Statin use may not prevent prostate cancer progression following radical prostatectomy. These findings do not provide support for the pursuit of a prospective clinical trial of statin use as a secondary prevention among surgically treated patients with prostate cancer.
研究 HMG-CoA 还原酶抑制剂(他汀类药物)在实验室研究中表现出广谱抗癌特性,是否与接受根治性前列腺切除术的前列腺癌患者复发风险降低相关。
通过 Kaiser Permanente Southern California(KPSC)癌症登记处,确定了 2004 年至 2005 年间诊断出的所有随后在 2005 年底前接受 KPSC 根治性前列腺切除术的患有前列腺癌的男性患者。对患者进行了长达 5 年的随访,随访终点为:(i)生化复发,定义为单一 PSA 测量值>0.2ng/ml;(ii)临床疾病进展,定义为转移性疾病或前列腺癌相关死亡的诊断。通过 KPSC 的电子病历,确定了他汀类药物使用情况、人口统计学、合并症、病理临床因素和结局等信息。使用双变量和多变量 Cox 模型同时检查了前列腺癌手术前后他汀类药物的使用效果,模型中调整了已知的预后因素。对于术后他汀类药物暴露情况,使用时间依赖性 Cox 模型。
共纳入 1200 名男性患者;37%的患者术前使用他汀类药物,56%的患者术后使用他汀类药物。术前或术后使用他汀类药物均与生化复发(风险比[HR]分别为 1.00[0.72-1.39]和 1.05[0.76-1.46])或临床疾病进展(HR 分别为 0.63[0.31-1.27]和 1.20[0.63-2.30])无关。也未发现使用时间与疗效之间存在明确的剂量反应关系。
他汀类药物的使用可能并不能预防根治性前列腺切除术后的前列腺癌进展。这些结果不支持在接受手术治疗的前列腺癌患者中开展他汀类药物使用作为二级预防的前瞻性临床试验。