Chavarriaga Julian, Lajkosz Katherine, Sangole Nishant, Penn Linda Z, Khurram Najia, Hamilton Robert J
Division of Urology, Department of Surgical Oncology, University Health Network & University of Toronto, Toronto, Ontario, Canada; Division of Urology, Cancer treatment and Research Centre (CTIC) Luis Carlos Sarmiento Angulo Foundation, Bogota D.C., Colombia; Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Division of Urology, Department of Surgical Oncology, University Health Network & University of Toronto, Toronto, Ontario, Canada; Division of Urology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Urol Oncol. 2025 Mar;43(3):193.e7-193.e17. doi: 10.1016/j.urolonc.2024.08.023. Epub 2024 Oct 29.
While observational studies suggest favorable associations between statin use and prostate cancer (CaP) outcomes, data from randomized-controlled trials remain inconclusive. Our study explores the relationship between statin use and survival outcomes in the context of the phase III ARAMIS study, a trial of darolutamide in the treatment of nonmetastatic castration-resistant prostate cancer.
We reviewed all 1,509 patients in the ARAMIS trial. Statin use was identified at baseline. Statin users were matched 1:2 with nonusers using a propensity score matching model. The primary endpoint was metastasis-free survival (MFS). Kaplan-Meier curves were plotted for MFS comparing statin users and nonusers across ARAMIS trial arms. A multivariate Cox proportional hazards model was fitted using the propensity-matched cohort and incorporating statin use and all covariates.
Of the 1,509 patients in ARAMIS, 334 (22.1%) were statin users. We matched 297 statin users to 550 nonusers. Characteristics appeared well balanced. Among nonusers, 331 (60.3%) and 219 (39.7%) were in the ARAMIS darolutamide and placebo arms, respectively. Among statin users, 179 (60.3%) and 118 (39.7%) were in the ARAMIS darolutamide and placebo arms, respectively. Overall, we found no significant difference in MFS between statin users and nonusers (HR 1.05, 95% CI 0.80-1.38 P = .72). However, we found significant interaction between statin use and ARAMIS trial arm. Specifically, statin use had a stronger association with MFS in the placebo arm (P = 0.024). However, this is likely coincidental and due to the statin-placebo patients having higher nodal positivity than the nonusers-placebo patients (14.3% vs. 5.5%). Statin use was similarly not associated with the secondary outcomes of PSA progression-free survival (P = 0.42), time-to-pain progression (P = 0.85), or overall survival (P = 0.15).
In our secondary analysis of the ARAMIS trial, statin users had similar MFS and secondary outcomes compared to nonusers. These results suggest pursuing further statin synergies with amide-based androgen receptor axis target agents may not be fruitful.
虽然观察性研究表明他汀类药物的使用与前列腺癌（CaP）预后之间存在有益关联，但随机对照试验的数据仍无定论。我们的研究在III期ARAMIS研究（一项达洛鲁胺治疗非转移性去势抵抗性前列腺癌的试验）背景下，探讨了他汀类药物的使用与生存预后之间的关系。
我们回顾了ARAMIS试验中的所有1509名患者。在基线时确定他汀类药物的使用情况。使用倾向评分匹配模型将他汀类药物使用者与非使用者按1:2进行匹配。主要终点为无转移生存期（MFS）。绘制了Kaplan-Meier曲线，用于比较ARAMIS试验各治疗组中他汀类药物使用者和非使用者的MFS。使用倾向匹配队列并纳入他汀类药物使用情况和所有协变量，拟合多变量Cox比例风险模型。
在ARAMIS的1509名患者中，334名（22.1%）为他汀类药物使用者。我们将297名他汀类药物使用者与550名非使用者进行了匹配。特征看起来平衡良好。在非使用者中，分别有331名（60.3%）和219名（39.7%）在ARAMIS达洛鲁胺组和安慰剂组。在他汀类药物使用者中，分别有179名（60.3%）和118名（39.7%）在ARAMIS达洛鲁胺组和安慰剂组。总体而言，我们发现他汀类药物使用者和非使用者之间的MFS无显著差异（风险比1.05，95%置信区间0.80-1.38，P = 0.72）。然而，我们发现他汀类药物使用与ARAMIS试验组之间存在显著交互作用。具体而言，他汀类药物的使用在安慰剂组与MFS的关联更强（P = 0.024）。然而，这可能是巧合，原因是他汀类药物-安慰剂组患者的淋巴结阳性率高于非使用者-安慰剂组患者（14.3%对 vs. 5.5%）。他汀类药物的使用同样与前列腺特异性抗原无进展生存期（P = 0.42）、疼痛进展时间（P = 0.85）或总生存期（P = 0.15）等次要结局无关。
在我们对ARAMIS试验的二次分析中，他汀类药物使用者与非使用者的MFS和次要结局相似。这些结果表明，寻求他汀类药物与基于酰胺的雄激素受体轴靶向药物的进一步协同作用可能不会有成效。
