Statins may be associated with lower prostate-specific antigen (PSA) levels, decreased prostate cancer incidence, and decreased mortality from the disease, according to data presented at the American Urological Association Annual Meeting.
There's the possibility that these drugs might have a role in reducing cancer progression or disease risk, said Anthony Smith, MD, Professor in the Department of Surgery, Division of Urology at the University of New Mexico Cancer Research and Treatment Center, who moderated a news conference that included the studies.
Patients might be more willing to use statins knowing they have another function, he said, adding that the drugs are being studied in a number of cancers in addition to prostate.
The data look very encouraging, but as with many studies, there are issues and problems, commented C.A. Stein, MD, PhD, Head of the Medical Genitourinary Oncology Program at Montefiore-Einstein Cancer Center and Professor of Medicine, Urology and Molecular Pharmacology at Albert Einstein College of Medicine, who was not affiliated with any of the studies.
Statins appear to reduce PSA levels in healthy men, suggesting that these drugs may have an impact on prostate biology, according to data (Abstract 463) presented by Robert Hamilton, MD, MPH, Associate in Research in the Department of Surgery, Division of Urology, at Duke University. The decline in PSA was most evident in men with the biggest declines in low-density lipoprotein (LDL).
Statins are a class of medications used to block cholesterol in the liver, which in turn reduces blood cholesterol and helps reduce negative cardiovascular outcomes, he noted, adding that statins such as atorvastatin (Lipitor) are widely prescribed in the United States.
Debate surrounds whether these medications have an impact on the risk of prostate cancer. Laboratory studies of statins show they can inhibit many of the processes of cancer cell growth and metastasis, but results in humans have not always been consistent.
Dr. Hamilton said that he and his colleagues theorize that these medications can lower PSA levels in healthy males, masking prostate cancer and interfering with early detection of the disease. If true, this could explain some epidemiological observations about the association between statins and prostate cancer risk, he said.
Figure. In the study...Image Tools
To quantify the influence of these medications on PSA levels in healthy men, the researchers studied 1,214 subjects prescribed a statin between 1990 and 2006 at the Durham Veterans Administration Medical Center. The mean age of subjects was 60.3, and median PSA was 0.9 ng/mL. Mean pre-statin LDL was 144 mg/dL.
Excluded were individuals with conditions that affect PSA, such as prostatitis or cancer, as well as medications that raise or lower PSA levels. After beginning statin treatment, subjects experienced a 28% median decline in LDL, and a 4.1% median decline in PSA.
The decline in PSA was proportional to the amount the statin lowered cholesterol in the patient, Dr. Hamilton said. Specifically, after a statin was started, PSA levels declined by 1.6% for every 10% decrease in LDL. This correlation was adjusted for age.
Also, subjects with the highest pre-statin PSA (i.e., 1.8 ng/mL or higher) and the largest drop in LDL (41.5% or more) had a median PSA decline of 15.2%. Among the 48 men with an LDL drop of more than 100 mg/dL, median PSA declined 22.6%.
The results suggest that statins influence prostate cancer biology, Dr. Hamilton said, cautioning, however, that it is much too premature to put perfectly healthy men on these medications to lower cancer risk. There can also be side effects such as muscle aches and changes in liver enzymes.
One drawback of this study was that it was retrospective, Dr. Stein noted. We also don't know how controlled the populations were.
Reviewing PSA levels among statin users screened in the Finnish Prostate Cancer Screening Trial, researchers from Helsinki found a decrease in prostate cancer incidence in these individuals, compared with those who did not take the drugs (Abstract 1719).
I believe that if study results like these are made known to men who are being treated with cholesterol-lowering drugs, it will be a motivation for them to use them as prescribed, said study presenter Teemu Murtola, MD, a researcher at the University of Tampere School of Public Health.
Most evidence surrounding statins' impact on prostate cancer is from laboratory studies, he noted. Some epidemiology studies indicate that statins may help to reduce prostate cancer risk, but other studies are conflicting.
The objective was to look at prostate cancer incidence and PSA levels in the presence of statins, and Dr. Murtola and his colleagues identified 78,484 Finnish men age 55 to 67 from the Population Registry. Of these, 30,196 were randomly assigned to prostate cancer screening.
By the end of the study period (1996-2004), three screening rounds had occurred and 23,320 men had been screened. Researchers obtained information on medication use from a database recording Finnish citizens' reimbursed drug purchases and found that about 29% used statins and other cholesterol-lowering medications.
Prostate cancer incidence was 2.8% among the 5,058 statin users and 4.7% among the 17,478 non-users, Dr. Murtola and his co-researchers reported. Additionally, the accumulative incidence of prostate cancer decreased among screened statin users in a dose-dependent manner.
The greatest decrease was for patients with T3 and Gleason sum 5 to 6 cancers, but a decrease in prostate cancer incidence was relatively similar in all categories of grade. The investigators also evaluated the use of other serum-lipid lowering drugs but did not find an association with prostate cancer incidence, stage or grade.
However, serum PSA was generally lower and the PSA free-to-total ratio was higher on both screening rounds in statin users as well as in those who used other serum lipid-lowering drugs. No correlation between PSA and the cumulative quantity of most lipid-lowering drugs was found.
Prostate cancer incidence was decreased among statin users, suggesting a chemopreventive effect when a large proportion of latent cancers are being found, the researchers said. In addition, statins and other types of serum cholesterol-lowering drugs may have an impact on PSA levels, Dr. Murtola said.
Studies such as this one will encourage scientists to find out the mechanism underlying the observed protective effect of statins, leading to better understanding of carcinogenesis of prostate cancer and ultimately to the development of prostate cancer preventive drugs.
The Finnish study did not prospectively randomize patients to statins and placebo, Dr. Stein commented. The study assessed people who were already on statins and those who weren't. However, conducting a prospective randomized trial of statins may be difficult because so many people are on these medications, he noted.
Figure. Teemu Murtol...Image Tools
Another drawback of the study is that it was done in just one country, and Finland is a little unusual because of its high-fat diet, Dr. Stein remarked, so whether the data can be extrapolated to the diverse population of the United States is unclear.
Results of another study (Abstract 203) showed a direct correlation between prostate-cancer mortality rates with hyperlipidemia and PSA screening in Caucasian men, as well as health insurance coverage in black males.
The link between high cholesterol and declining mortality was unexpected, wrote the study authors, led by Janet Colli, MD, Assistant Professor of Surgery at the University of Alabama at Birmingham and Chief of Urology at the Veterans Administration Hospital there. This decline might be due to the increased use of statins in these men.
Prostate cancer mortality rates increased in the 1980s, but have steadily decreased from 1993 to now, Dr. Colli noted in her presentation of the results. PSA screening and prostate cancer treatments contributed to the decline but may not have been the sole cause, so the goal was to identify other contributing factors.
The researchers obtained annual rates of prostate cancer mortality for men older than age 50 from the National Vital Statistic System for the continental US from 1993 to 2003. Prostate cancer mortality rates were compared with the rates of PSA screening, health insurance coverage, obesity, and physical inactivity in white and black men, as well as the incidence of diabetes and hyperlipidemia levels among white and black men.
For Caucasian males, investigators found that declining prostate cancer mortality rates were correlated with high cholesterol levels and PSA screening levels.
In addition, declining prostate cancer mortality rates for black men correlated with health insurance coverage.
The smaller impact of prostate cancer screening among black men may be related to lower access to health care and subsequent lower rates of prostate cancer screening, Dr. Colli said. In addition, the declining prostate cancer mortality rate among Caucasian men associated with high cholesterol may be due to the increased use of statins in these individuals.
Statins have been shown to have antiproliferative activity among prostate cancer cells in vitro and may reduce prostate cancer risk among men taking them, the researchers wrote.
Overall, statins are a proven heart-healthy agent, and further studies are needed to access if they also have a benefit against prostate cancer, Dr. Colli noted.
The research presented by Dr. Colli on decreasing mortality rate was pretty powerful, Dr. Smith said. Such data suggest that using statins over a period of time may be a potential option for chemoprevention.
Despite this study indicating that statins might play a role in prostate mortality decline, a lot of other factors need to be considered, Dr. Stein commented. For example, a lot of men were having digital rectal exams and PSA testing during the time the study was conducted, and this probably saved many lives, he explained.
What to Tell Patients
Despite the evidence presented in these studies, physicians should not recommend statins as a preventive measure for men with an average or high risk of prostate cancer, said C.A. Stein, MD, PhD, Head of the Medical Genitourinary Oncology Program at Montefiore-Einstein Cancer Center and Professor of Medicine, Urology and Molecular Pharmacology at Albert Einstein College of Medicine. Dr. Stein, who was not affiliated with any of the studies, was asked for his perspective on the research for this article.
Definitive studies are needed before statins can be prescribed as a cancer preventive or treatment, he said.
An important issue that needs to be considered, regardless of which study is being discussed, is the toxicity of statins, he said. Although the toxicity of statins is low, they are not non-toxic, he explained.
Overall, these drugs are widely used and have well-known side effect and tolerability profiles, noted the moderator of a news conference at the AUA meeting that featured the studies, Anthony Smith, MD, Professor in the Department of Surgery, Division of Urology at the University of New Mexico Cancer Research and Treatment Center. Still, like Dr. Stein, he is not willing to tell patients they should take statins to prevent prostate cancer.
Dr. Smith said that instead, he discusses patients' cholesterol levels, and if the levels are high, he asks patients if they have thought about taking statins, especially if they also have elevated PSA levels.
© 2007 Lippincott Williams & Wilkins, Inc.