[2015 ASCO GU]他汀类药物可延长去势治疗前列腺癌患者TTP

发布时间:2015-02-27 浏览次数:491次 来源: 作者:

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2015泌尿生殖系统肿瘤研讨会(ASCO GU)于2月26日至28日在美国奥兰多举行。在本次会议上展出的一项研究,分析了在开始雄性激素去势治疗时他汀类药物使用与至疾病进展时间(TTP)的关系(摘要号148)。医脉通对此进行了报道。


应用他汀类药物与前列腺癌局部治疗后复发风险的降低及死亡风险的降低相关。然而对于他汀类药物的使用与开始接受雄性激素去势治疗 (ADT)患者的前列腺癌进展之间的相关性,目前尚不明确。


研究人员查询了研究临床数据库(Prostate CRIS)。该数据库囊括了前列腺癌患者的临床人口统计数据,治疗详情及临床结果。研究人员利用该数据库识别了接受雄性激素去势治疗患者的生化复发或转移性疾病,并通过医学记录,收集了进展日期和开始雄性激素去势治疗时他汀类药物的使用情况。将进展定义为3次PSA升高。将进展日期定义为第一次升高的日期(nadir + >0.02 ng/ml)。利用多变量Cox回归估计雄性激素去势治疗下的他汀类药物使用与至疾病进展时间的相关性。并根据已知的预后因素进行调整。这些因素包括:活检Gleason评分,首次治疗类型,转移状态及开始雄性激素去势治疗时的PSA。


该分析中926位符合条件的患者中,有283位(31%)在开始雄性激素去势治疗时使用了他汀类药物。使用他汀类药物的患者与不使用他汀类药物的患者相比,诊断为M1 (11 vs. 18%)或N1 (5 vs 10%)疾病的可能性更低,并且更可能接受局部治疗+/-ADT。


使用他汀类药物的患者在开始雄性激素去势治疗时发生转移的可能性更低(53 vs 63%)。他汀使用者确诊时和开始雄性激素去势治疗时的中值PSA更低,且从确诊到ADT开始的时间间隔更长。


中位随访5.8年后,644位患者(70%)经雄性激素去势治疗后发生进展,雄性激素去势治疗下的中位TTP为20.3个月(95% CI: 18,24)。他汀使用者与不使用他汀类药物的患者相比,雄性激素去势治疗下的中位TTP更长(27.5 vs 17.4 个月)。在调整了已知预后因素后,相关性仍有统计学显著差异[调整HR=0.83 (p=.039)]。


在该研究中,在开始雄性激素去势治疗时使用他汀类药物与雄性激素去势治疗下TTP的显著延长相关(即使在调整了预后因子后)。针对此现象背后机制的进一步研究正在计划中。


英文摘要


Background: Statin use has been associated with a decreased risk of recurrence after local therapy and a lower risk of prostate cancer mortality. There is little known about the association between statin use and prostate cancer progression among men newly initiating ADT. We undertook an analysis of the association between statin use at the time of ADT initiation and TTP.


 Methods: We queried our institutional clinical database (Prostate CRIS), which captures clinicodemographic data, treatment details, and clinical outcomes of our prostate cancer patients (pts), to identify pts treated with ADT for biochemical recurrence or metastatic disease. Date of progression and statin use at ADT initiation were collected by medical record review. Progression was defined as 3 PSA rises. Date of progression was defined as date of first rise (nadir + >0.02 ng/ml). The association between statin use and TTP on ADT was estimated from multivariable Cox regression, adjusting for known prognostic factors: biopsy Gleason score, primary therapy type, metastatic status, and PSA at ADT initiation. 


Results: Of the 926 patients eligible for analysis, 283 (31%) were taking a statin at ADT initiation. Statin users were less likely to have M1 (11 vs. 18%) or N1 (5 vs 10%) disease at diagnosis and more likely to have received local therapy +/-ADT compared to nonusers. They were also less likely to have metastases at ADT initiation (53 vs 63%). Median PSA at diagnosis and at ADT initiation were lower among statin users. Duration from diagnosis to ADT initiation was longer in users. After a median follow-up of 5.8 years, 644 pts (70%) had progressed on ADT and median TTP on ADT was 20.3 months (95% CI: 18,24). Men on statins had a longer median TTP on ADT compared to nonusers (27.5 vs 17.4 months). The association remained statistically significant after adjusting for known prognostic factors [adjusted HR=0.83 (p=.039)]. 


Conclusions: In our cohort, statin use at the time of ADT initiation was associated with a significant increase in TTP on ADT even after adjusting for established prognostic factors. Further investigation into the mechanisms behind this observation is planned.