Abstract

Abstract Background: Statins have been shown to possess anti-cancer properties and their use has been associated with reduced cancer mortality. Several prior studies found inverse associations between statin use and risk of biochemical recurrence of prostate cancer (PCa). There is, however, little research on the impact of statin use post PCa diagnosis on risk of metastasis among men on active surveillance. A potential preventive effect of post-diagnostic statin use can have implication for managing PCa in those patients. Here we examined the association between statin use and risk of metastasis in men with untreated localized PCa. Methods: Men diagnosed with PCa at Kaiser Permanente Southern California (KPSC) between 1997 and 2007 who met the following inclusion criteria were included in this retrospective cohort: (1) diagnosed at stage I and II; (2) Gleason grade ≤ 7; and (3) did not have any active treatment for PCa for at least 6 months after diagnosis. All men were followed to identify PCa metastasis and were censored at the initiation prostatectomy or radiation, non-PCa related death, termination of KPSC membership, or end of 2016. Potential metastasis was initially captured based on diagnosis codes, utilizations and cause of death, then manually reviewed and confirmed. Data on statin use and other clinical history were collected from KPSC's electronic medical records. Time-dependent Cox regression was used to evaluate the association between post-diagnostic statin use and risk of metastasis, adjusting for statin use prior to PCa diagnosis, index year at diagnosis, age at diagnosis, prostate-specific antigen level at diagnosis, use of hormone therapy, hypertension, and diabetes. A sensitivity analysis was conducted excluding men with statin use prior to PCa diagnosis. Results: A total of 4,326 men were included in this cohort study. During the study follow-up, 207 men developed metastasis while still untreated. The mean age at diagnosis was 67.5 years. The cohort is racial/ethnically diverse: 59% non-Hispanic white, 14% Hispanic, 20% black and 5% Asian. Thirty-one and forty-nine percent used statins before and after PCa diagnosis, respectively. In Cox regression, post-diagnostic statin use was not associated with the development of metastasis: Hazard ratio = 0.94 (95% confidence interval 0.69-1.29) after adjusting for covariates. There was no evidence of dose-response for the proportion of at-risk person-time post PCa diagnosis on statins. In addition, statin use prior to diagnosis was also not associated with risk of metastasis (HR=0.88 (0.62-1.23)). Sensitivity analysis excluding men who used statins prior to PCa diagnosis led to similar findings. Conclusion: Statin use after the diagnosis of localized PCa was not associated with lower risk of metastatic progression in this large cohort of untreated men. This finding does not support the chemopreventive use of statins for men with PCa on active surveillance. Citation Format: Chun R. Chao, Yu-Hsiang Shu, Jeff Slezak, Kimberly L. Cannavale, Gary Chien, Stephen Van Den Eeden. Statin use and risk of metastasis in a cohort of men with untreated localized prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3515.

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