PSA tests, statin use, and prostate cancer: Persistent questions

It's no surprise to prostate cancer survivors: the PSA test saves lives. A study published in the November/December 2008 issue of Urologic Oncology found evidence that "PSA screening and treatment of high risk prostate cancer patients is associated, at least in part, with the significant decline in prostate cancer mortality … for white males" in the United Stated between 1993 and 2003. (Among black males, declining prostate cancer mortality rates correlated with having health insurance coverage rather than with PSA screening.)

This study by Dr. Janet Colli and Dr. Christopher Amling set out to answer a persistent question. Why, following the introduction of PSA screening in the United States in 1989, did prostate cancer deaths increase between 1989 and 1993 and then decrease between 1993 and 2003? The two compared prostate cancer mortality rates with the rates of PSA screening, health insurance coverage, obesity, and physical inactivity in white and black men, as well as with the incidence of diabetes and high cholesterol among white and black men. (Click here to see an abstract of this study.)

They thought that the initial increase in mortality could have been caused by misattribution bias. In other words, because more men were living with a diagnosis of prostate cancer after the institution of the PSA test, and this circumstance was new for the medical profession, some proportion of these men were said to have died of prostate cancer although they died of other causes. The finding that the PSA test does, in the long run, help reduce prostate cancer mortality rates is consistent with the results of an earlier study led by Dr. Pamela Shaw. She and her colleagues found a weak but present statistical trend: geographic areas with greater PSA screening rates had greater declines in prostate cancer mortality. (See this study.)

But Colli and Amling happened upon another interesting statistical connection during the course of their research. "There was a very strong correlation between declining prostate cancer mortality rates and declining high cholesterol levels in white males," Colli said. The doctors think that statin use among men diagnosed with hyperlipidemia (high cholesterol levels) may be one significant reason for this decline.

Statins are drugs that reduce blood cholesterol by blocking the action of an enzyme in the liver called HMG-CoA reductase, which controls cholesterol production. But some studies suggest that statins affect PSA levels and prostate cancer risk and mortality as well.

A research team led by Dr. Robert J. Hamilton, now a urologist at the University of Toronto, found an average 4.1 per cent decline in PSA among men who were started on a statin drug. Also, the higher the dose, the more the PSA dropped. And the men whose PSA was highest experienced the greatest drop. "These men had an average of a 15 per cent drop in their PSA," Hamilton notes.

What is still not clear, though, is how statins affect the prostate and prostate cancer. Does this documented drop in PSA with statin use correspond to better health outcomes for men, or does it happen without affecting prostate cancer growth and risk? Dr. Hamilton elaborates. "In a good proportion of these men, the PSA levels declined sufficiently to a point where physicians might not recommend a biopsy, so it's really important that we understand what's at work here, so we can be sure we're not missing cancers because of deceptively low PSA levels."

Still, most researchers are theorizing that statins, by affecting not only cholesterol synthesis but also testosterone production, cell signalling pathways, and inflammation, may help reduce prostate cancer risk. Some have even suggested that the drugs may play a role in changing prostate cancer cell membranes, which are rich in cholesterol.

Researchers from Helsinki would agree that statins seem to have a direct effect on prostate cancer risk. In 2007, the Finnish Prostate Cancer Screening Trial reported a significant decrease in the incidence of aggressive prostate cancer among trial participants who took statins. Prostate cancer incidence was 2.8 per cent among the 5,058 statin users and 4.7 per cent among the 17,478 non-users. But the greatest decrease was for patients with T3 and Gleason sum 5 to 6 cancers. (Read this article.)

The data from the Finnish study confirm earlier findings. In 2006, Dr. Elizabeth Platz and other researchers at Johns Hopkins and Harvard reported that men who took a statin drug for less than five years had a 40 per cent lower risk of developing advanced prostate cancer, and men who used a statin for at least five years had a 70 per cent lower risk. Interestingly, use of statin drugs did not affect overall risk of developing prostate cancer, only the risk of developing "advanced and high-grade disease." (See an abstract of this article.)

But we still have a lot to learn about the relationship between statins and prostate cancer. Some studies have found no connection between statin use and prostate cancer risk. And two studies even suggested that use of these drugs is linked to an increase in the overall risk of developing prostate cancer. A recent article published in the American Journal of Epidemiology reported an increased risk associated with statin use among obese men, particularly use for extended durations, although findings did not indicate any overall association between statin use and prostate cancer risk.

Statins, although promising, have a long way to go before they are considered "the aspirin of the 21st century," as reported in a recent CBC story. Still, men with prostate cancer (or at high risk of developing the disease) might want to keep their finger on the pulse of statin research.

For current information:

Hamilton, R. J., Goldberg, K. C., Platz, E. A., & Freedland, S. J. (2008). The influence of statin medications on prostate-specific antigen levels. Journal of the National Cancer Institute, 100, 1511-1518. (The full text of this article is available.)

Murtola, T.J., Visakorpi, T., Lahtela, J., Syvälä, H., & Tammela, T. L. (2008). Statins and prostate cancer prevention: Where we are now, and future directions. Nature Clinical Practice Urology, 5(7), 376-387. (The full text of this article is available.)