Assessing the Relationship between Statin Use and Oncologic Outcomes Among Men Electing Active Surveillance for Localized Prostate Cancer

There has been an increase in the use of active surveillance (AS) over the last 5-10 years. However, the rate of treatment among men electing AS is approximately 50% at 10-years. This raises the question: is there an intervention that can delay disease progression and/or prevent the need for intervention? One potential therapeutic agent that could be considered are HMG-CoA reductase inhibitors—also known as statins. Data from most clinical trials demonstrate that statin use, in a dose-dependent manner, is associated with a reduced risk of advanced prostate cancer. However, there is limited evidence regarding the role of statins among men electing AS.

To investigate this relationship further, we conducted a retrospective cohort study on men managed with AS from 2005-2015. The primary endpoints of analyses included the rate of disease reclassification, progression to definitive therapy, and surveillance failure—defined as a biochemical failure after definitive treatment, metastases, and prostate cancer-specific mortality—among statin and non-statin users. Furthermore, we performed a logistic regression analysis in order to assess the impact of statin use on oncologic outcomes following definitive treatment.

635 patients were included in the study and 56.1% used statins at the initiation of AS. Statin users were older and had a longer median follow-up (44.8 vs. 58.3 months, respectively; p<0.001) compared to non-users. On univariate analysis, there was no significant difference in the rates of disease reclassification (56.5% vs. 58.4%) and progression to definitive treatment (48.5% vs. 41.7%) at 10-years between the two groups. 10-year cumulative freedom from AS failure was 89.8% and 92.6% among statin and non-statin users, respectively (p > 0.05). 105 men progressed to treatment with radical prostatectomy and 47.6% were statin users. There was no significant difference in the rates of adverse pathology (i.e. primary Gleason grade pattern 4 or any pattern 5, extra-prostatic extension, seminal vesicle invasion, or lymph node invasion) after prostatectomy between statin and non-statin users. However, duration of statin use was inversely correlated with adverse pathology for radical prostatectomy on multivariate analysis (OR 0.98; 95% CI 0.97, 0.99) when adjusted for age at treatment, initial PSA, and preoperative Gleason score.

Statin use was not associated with a decreased risk of disease reclassification, progression to curative treatment, or surveillance failure among men managed by AS. These findings are similar to those reported by Jayalath et al.¹ However, we demonstrate that among men who progressed to radical prostatectomy, there was a 2% decreased odds of adverse pathology at radical prostatectomy for each month of statin use. Data from larger prospective studies are needed to better characterize the relationship between the duration of statin use and both oncologic and pathologic findings among men managed with active surveillance for favorable-risk prostate cancer.

Written by: Lamont J. Wilkins, and Yaw A. Nyame, MD, MBA, Department of Urology, Glickman Urologic and Kidney Institute, Cleveland Clinic. Cleveland, Ohio; Department of Urology, University of Washington, Seattle, Washington.

References:
1. Jayalath et al, Statin use and time to progression in men on active surveillance for prostate cancer, Prostate Cancer and Prostatic Diseases, 2018, doi: 10.1038/s41391-018-0053-x.

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