Prostate cancer recurrence risk reduced with post-radical prostatectomy statin therapy

September 1, 2010

Postoperative statin use may offer a potential therapeutic benefit in men with prostate cancer who undergo radical prostatectomy.

The analyses were based on 1,280 men with prostate cancer treated surgically between 1988 and 2009 at Veterans Affairs sites comprising the Shared Equal Access Cancer Research Hospital (SEARCH) database who were not on any statin medication prior to RP. Postoperatively, 350 men (27%) initiated statin treatment.

Time to biochemical recurrence was compared between statin users and nonusers using a Cox proportional hazards regression analysis, adjusting for various demographic, clinical, and pathologic parameters and treating statin intake as a time-varying covariate, considering the variability within the population in the time between surgery and initiation of statin intake.

In univariate analysis, statin users had a significantly lower risk for biochemical recurrence relative to nonusers (hazard ratio: .75; p=.047), and the benefit of post-RP statin treatment was maintained in the multivariate analysis (adjusted HR: .61; p=.02).

"As a retrospective study, it has a number of limitations because there may be important differences between statin users and nonusers that we cannot account for, such as in diet, lifestyle, health-seeking behaviors, incidental co-morbidities, and postoperative follow-up intensity," said Dr. Bañez, who presented the findings at the AUA annual meeting in San Francisco. "Further studies are needed."

Senior author Stephen Freedland, MD, noted that in a previous prospective study of 1,200 men, initiation of statin use was associated with a statistically significant median PSA decline of 4% (JNatl Cancer Inst 2008; 100:1511-8). Therefore, modeling was undertaken to investigate whether a PSA-lowering effect of statin treatment might be interfering with the endpoint of PSA recurrence in the present study.

"Our analyses showed it cannot explain the 39% risk reduction associated with statin use," said Dr. Freedland, associate professor of urology and pathology at Duke.

In the current study, biochemical recurrence was defined as any post-RP PSA >0.2 ng/mL, two PSA determinations of 0.2 ng/mL, or receipt of any secondary treatment due to rising PSA.

The multivariate model controlled for age, race, PSA, year of RP, body mass index, biopsy and pathologic Gleason sum, surgery center, margin/capsule/seminal vesicle status, lymph node involvement, and prostate specimen weight. Comparisons between the statin users and nonusers showed significant differences in several of these characteristics, Dr. Bañez reported.

"Relative to the nonusers, statin users were younger on average and had a higher BMI, a lower median preoperative PSA, less advanced stage disease at the time of RP, and a lower positive margin rate," he said.

Dr. Bañez noted that possible mechanisms for a therapeutic effect of statins against prostate cancer include lowering of cholesterol and inhibition of inflammation.