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Statins and prostate tests

Wednesday 29 October 2008

“Statin drugs taken by millions of men could dampen a key indicator of prostate cancer,” reported the Daily Mail today. It warns that a new study has found that when men take statins they experience a significant drop in blood levels of a protein marker (prostate specific antigen) used to help diagnose cancer. The worry is that this drop in PSA levels may mask cancer, and men with the disease go undiagnosed.

The study on which this story is based cannot prove whether the declining levels of PSA associated with statin treatment are due to a reduction in prostate cancer risk, or whether they are masking cancer. Until further results from prospective studies are available, the benefits of statins for men at high risk of cardiac events (such as the men in this study) outweigh possible harms. In the UK, PSA testing is not routinely carried out, but usually only done after symptoms have been reported and a clinical examination carried out. The results are then interpreted, taking all known factors into account. On its own, PSA testing is thought to be too unreliable a test for prostate cancer screening.
All men – taking statins or not – who are experiencing persistent urinary problems should consult their doctor.

Where did the story come from?

Dr Robert J. Hamilton and colleagues from Duke University School of Medicine in North Carolina, US carried out the research. The study was supported by the Department of Veterans Affairs, the Department of Defense Prostate Cancer Research Program, and the American Urological Association Foundation/Astellas Rising Star in Urology Awards. The study was published in the peer-reviewed medical journal: Journal of the National Cancer Institute.

What kind of scientific study was this?

The researchers say that there is conflicting evidence that statins may be associated with a reduced risk of prostate cancer. However, it is unknown what effect statins have on levels of prostate-specific antigen (PSA), which is used in the diagnosis of prostate cancer. Statins are used to lower cholesterol in order to prevent conditions such as heart disease and stroke.

This was a case series study of the records of 1,214 men who were prescribed a statin between 1990 and 2006 at the Durham Veteran Affairs Medical Centre. All of the men were free of prostate cancer for the duration of the study, and had never had prostate surgery or taken any medications that might have altered their androgen (male hormone) levels. The researchers excluded men who had very high levels of PSA, men who had undetectable levels before taking statins, and men whose PSA levels after statin treatment were undetectable, in case these men may represent missed cases of prostate cancer or treatment. The only men included were those who had their PSA levels measured and recorded within two years before statin treatment and another measure within one year after starting statins. Of the original 23,428 men who started taking statins at this medical centre between 1990 and 2006, only 1,214 men were included after excluding for missing data, prostate cancer diagnosis or treatment, and other factors.

The researchers were interested in assessing whether PSA levels were different before and after taking statins, and whether the degree of change was linked to changing levels of cholesterol (low-density lipoprotein [LDL], high-density lipoprotein [HDL], and total cholesterol). Their analysis adjusted for (took into account) other factors that may have had an affect, including age, initial statin dose, changes in statin dose, ethnicity, BMI, concentration of PSA before statins, time between first and second PSA measurements, and the year in which statin treatment commenced. For the men who had more than one PSA measure before starting statins it was possible to analyse changes in PSA levels that might occur anyway.

What were the results of the study?

The researchers noted that the participants averaged 60 years and the majority were caucasian (60%) and either overweight or obese (85%). The median (average) change in PSA levels after starting statins was a decline of 4.1%. For half the participants, this ranged from -22.1%  to +12.5% (i.e. an increase in PSA levels).

When the researchers looked at cholesterol and PSA, there appeared to be a direct relationship between decreasing LDL levels and decreasing PSA levels. For every 10% reduction in levels of LDL, PSA declined by 1.64%. In men who had more than two measures of PSA before statins, there was no change between these two pre-statin PSA levels. Changes in HDL levels were not associated with changes in PSA.

The researchers also conducted further analyses of the men whose pre-statin PSA measures were at levels that warranted further investigation for cancer, including biopsy. They found that in men  whose PSA levels had been 4ng/mL before taking statins (i.e. in whom a biopsy might be indicated), levels dropped in 39% of them after starting statins. There were also reductions in numbers with levels of 3ng/mL and 2.5ng/mL before statins, (26% and 24% respectively). In these three groups, PSA levels reduced below the thresholds that might indicate that further investigations were necessary.

What interpretations did the researchers draw from these results?

After starting statins, men’s PSA levels declined by a median of 4.1%; a significant drop when compared with the lack of change in repeated PSA measures before statins. The authors conclude that “the PSA declines with statin use…may represent objective evidence of statins influence on prostate biology in support of epidemiological studies suggesting statins reduce overall or advanced prostate cancer risk”. Or alternatively, they say that risk of prostate cancer may not change, but given that PSA levels are monitored as part of prostate cancer detection, the associated reduction in levels alongside statin treatment may complicate cancer detection.

What does the NHS Knowledge Service make of this study?

There are several important points to bear in mind when interpreting the results of this study.

  • Firstly, the news report does not mention the alternative explanation of these results, that statins protect against prostate cancer (hence the decline in PSA levels). This is a theory that the researchers discuss at length, and which has also been suggested by other studies. If this were the case, then it would be an additional benefit of statins, rather than the other interpretation that potential cases of prostate cancer are being missed. Only further study in prospective cohort studies that have a proper control group will clarify this issue.
  • The point about a ‘control group’ is important. In this study, the researchers used medical records to assess changes in PSA levels from before and after statin treatment. There was no parallel group of similar men not taking statins with whom fluctuating PSA could be compared. PSA levels increase with age and can change for other reasons, therefore in such studies it is important that a similar group of men are assessed to see whether statins really are responsible.
  • The researchers attempted a control, using men from the larger cohort who had two PSA tests before statin treatment. They compared the difference between these with the difference between the pre- and post-statin levels. This is not an ideal control because the qualities that make these men candidates for statin treatment means they have different characteristics from men who are not prescribed these drugs.
  • The participants in the analysis do not represent all the men who took statins through this medical centre. This raises issues of selection bias – i.e. that this group may be systematically different from the larger cohort.

The results of this study are important mainly because they bring attention to an area for further research. Men who currently take statins should not be alarmed by these findings. The study does not prove that PSA tests are made less accurate by statins.

Most importantly, the Daily Mail quote by Dr Freedland, who led the research, that “this PSA decline may complicate screening” and that “cancers may be missed due to lower PSA levels [in men taking statins]”, reflects the US situation and not the UK one. In the UK, nationwide PSA screening is not carried out. Prostate conditions are first suspected on the basis of symptoms and clinical examination, after which PSA testing is carried out. All these factors are taken into account when the test’s results are interpreted. Treatment is therefore based on more than just a laboratory result, which is not 100% reliable.

All men – taking statins or not – who are experiencing persistent urinary problems should consult their doctor.

Sir Muir Gray adds...

I don't think this is a major worry.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Why taking statins could mask signs of prostate cancer.

Daily Mail, 29 October 2008

Links to the science

Further readingThere are a number of Cochrane reviews about interventions for prostate cancer and one that considers screening: Ilic D, O'Connor D, Green S, Wilt T.

Screening for prostate cancer.

Cochrane Database Syst Rev 2006, Issue 3

Hamilton RJ, Goldberg KC, Platz EA, Freedland SJ.

The Influence of Statin Medications on Prostate-specific Antigen Levels.

Journal of the National Cancer Institute 2008; Advance Access published online on October 28, 2008