Experts Push for Trials of Statins to Prevent Prostate Ca

July 1, 2007

Statins, but not other lipid-lowering drugs, are associated with reduced rates of prostate cancer, have their greatest effect on stage T3 cancers, and may act in part by altering prostate gland biology

ANAHEIM, California—Statins, but not other lipid-lowering drugs, are associated with reduced rates of prostate cancer, have their greatest effect on stage T3 cancers, and may act in part by altering prostate gland biology, according to research presented at the 102nd Annual Scientific Meeting of the American Urological Association. The researchers argued strongly for large-scale trials of statins for prevention of prostate cancer. Among the studies:

• Janet L. Colli, MD, and colleagues from the University of Alabama at Birmingham found that declining prostate cancer mortality rates for white males in the United States correlated with high cholesterol levels. They doubt that this is because cholesterol prevents cancer, suggesting instead that the protective effect might be due to widespread use of statins in this group (abstract 203).

• Teemu J. Murtola, MD, and colleagues from the University of Tampere, Finland, added substance to this idea with data from a screening study of 23,320 men showing that those taking statins had only half as many prostate cancers as those not taking statins (abstract 1719).

• Robert J. Hamilton, MD, and colleagues at the Durham Veterans Affairs Medical Center and Duke University found that even in normal men, statins significantly reduce PSA levels and so probably alter prostate biology (abstract 463). Dr. Hamilton urged further study of statins for prevention of prostate cancer but also raised the concern that the PSA-lowering effect might interfere with prostate cancer detection.

Dr. Colli's study used data from the National Vital Statistics System to determine the rate of prostate cancer mortality decline for the years 1993 to 2003 for each of the 48 continental states. The annual rate of prostate mortality decline for each state was then cross-correlated with rates of PSA screening, health insurance coverage, obesity, physical inactivity, diabetes, and hyperlipidemia or high cholesterol.

The analysis revealed a strong correlation in white men between declining prostate cancer mortality and PSA screening (R = -0.28, P = .05) and elevated cholesterol levels (R = -0.42, P = .002). Declining prostate cancer mortality rates for black men in the study correlated only with health insurance coverage (R = -0.43, P = .03). "Future large-scale prostate cancer prevention trials examining the effects of statin use on risk of prostate cancer and prostate cancer mortality need to be conducted," Dr. Colli concluded.

Dr. Murtola and colleagues studied all screened participants of the Finnish Prostate Cancer Screening Trial during 1996 to 2004 (23,320 men) with detailed information on cholesterol drug usage during that time period. There were three screening rounds during the study period, and each man was screened for PSA at least once. The researchers correlated these subjects' prostate cancer status with their medication use, obtained from the Social Insurance Institution of Finland database.

This showed a prostate cancer incidence of 4% among the statin users (n = 6,755) vs 8% among the nonusers (n = 16,565) (incidence ratio 0.48; 95% CI 0.42-0.54). Decreased prostate cancer incidence was observed for all categories of grade. "The cumulative incidence of prostate cancer decreased among screened statin users in a dose-dependent manner. The greatest decrease was observed for T3 cancers," Dr. Murtola said. This effect was associated only with the use of statins and not with other lipid-lowering drugs (fibrates or resins). Serum PSA was lower among users of all groups of cholesterol drugs, compared with nonusers. However, there was no correlation between PSA and the total quantity of drug usage.

He said the results, albeit preliminary, suggest that statin drugs "do have prostate cancer preventive potential." The fact that PSA decreased among users of all types of cholesterol drugs "suggests that the observed effect is likely not due to drug use but more probably to some factor common to all cholesterol drug users."

Could Statins Hinder Detection?

Dr. Hamilton's study was meant to address the question of whether statins might lower PSA values in healthy men and thus hinder early detection by masking prostate cancer.

The researchers studied 1,545 men who had been prescribed a statin between 1990 and 2006. After exclusions for other factors that could affect PSA (eg, prostate cancer, prostatitis, testosterone supplementation), the researchers reported data for 1,214 men.

All of the men had at least one PSA test within the 2 years before beginning statin therapy, and had at least one PSA value within 3 years after beginning statins. The study endpoints were pre-and post-statin PSA level and percent change in PSA level. "The average patient experienced a 4.1% decline in PSA after starting statins. Compare this to current understanding of the natural history of PSA, which shows that the average PSA rise is 3% to 13% over 1 year," Dr. Hamilton said.

He reported that PSA dropped more in men who used higher doses of statins, had higher PSA before starting statins, and in whom statins caused a larger drop in cholesterol. The largest PSA decrease (15.2%) was in patients who had the highest pre-statin PSA (1.8 ng/mL or higher) and the largest drop in cholesterol after starting statins (41% or more). "These findings support further study of statins in preventing prostate cancer," he said. "For every 10 mg/dL decrease in LDL after starting a statin, PSA levels declined by 1.1% (P < .001), adjusted for age."

The question of whether statin treatment might be interfering with prostate cancer detection was not clearly answered, however. Dr. Hamilton concluded that the average 4% decline in PSA is unlikely to affect cancer detection but that there might be prostate cancer detection problems in patients who have "a big drop in cholesterol after starting a statin."