February 6, 2009

Prostate Cancer: Who’s at Greatest Risk?

Due to the limitations of traditional screening tests for prostate cancer, researchers continue to search for more accurate ways of determining who is at increased risk of prostate cancer and who should undergo prostate biopsy. Two recent studies explored the use of tests that could reduce the rate of unnecessary prostate biopsies, and a third study evaluated a potential genetic marker of increased prostate cancer risk.

Men 50 years or older in the U.S. are often offered prostate-specific antigen (PSA) testing for the early detection of prostate cancer. The PSA test measures proteins that are produced and shed by the prostate. PSA levels tend to be elevated when prostate cancer is present, but levels can also be elevated in benign (non-cancerous) conditions affecting the prostate.

In response to the limitations of traditional PSA testing, researchers have explored alternative approaches; these include measuring the rate of change of PSA or measuring different forms of PSA. For example, PSA in the blood is either bound to proteins (complexed) or free. The traditional PSA test tests for total PSA, which includes both complexed and free PSA. Some have suggested, however, that levels of complexed PSA are more closely linked with prostate cancer. Thus, testing specifically for complexed PSA may more accurately screen for prostate cancer.

To compare the performance of tests for total PSA to tests for complexed PSA, researchers in Germany evaluated available data using a new statistical technique.[1] The researchers found that tests for complexed PSA outperformed tests for total PSA in two important areas: positive predictive value (the probability of having cancer among those who have a positive screening test) and specificity (the probability of correctly classifying individuals who are cancer free). The researchers estimated that using complexed PSA instead of total PSA could avoid more than 10% of unnecessary biopsies among men with total PSA in the range of 3 to 5 ng/ml.

A second study assessed whether information about several patient characteristics, in addition to PSA level, can improve estimation of cancer risk.[2] The study involved more than 5,000 men, all of whom underwent prostate biopsy regardless of their PSA level. Factors that were linked with a higher probability of finding cancer at biopsy were higher PSA level, a positive family history of prostate cancer, and an abnormal digital rectal exam result. Having a previous negative biopsy was linked with a lower probability of having cancer.

The researchers suggest that these findings may be used to estimate an individual’s risk of prostate cancer, and to guide decisions about when a prostate biopsy is warranted. An accompanying editorial, however, notes that the current study may have detected a disproportionate number of non-life-threatening cancers, and that applying the risk-estimation tool developed by the study may further contribute to the over-diagnosis of prostate cancer.[3]

Finally, in a third study, researchers reported that they may have identified a genetic variant, located on chromosome 8,  that increases the risk of developing prostate cancer.[4] Among men of European ancestry, the genetic variant was identified in 19% of men with prostate cancer and 13% of men without prostate cancer. Among African-American men, the genetic variant was identified in 41% of the men with prostate cancer and 30% of the men without prostate cancer. The genetic variant may account for 8% of prostate cancers in men of European descent and 16% of prostate cancers in African-American men.

The researchers conclude that the higher frequency of this genetic variant in African-American men may partially explain the higher risk of prostate cancer among African-Americans. Tests for this genetic variant could help identify men who would benefit from earlier or more frequent prostate cancer screening.

If confirmed, the results of these studies will help men and their physicians make decisions about the frequency and type of prostate cancer screening and the need for prostate biopsy.


[1] Jung K, Lein M, Butz H et al. New Insights Into the Diagnostic Accuracy of Complexed and Total Prostate Specific Antigen Using Discordance Analysis Characteristics. The Journal of Urology. 2006;1275-1280.

[2] Thompson IM, Ankerst DP, Chi C et al. Assessing Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial. Journal of the National Cancer Institute. 2006;98:529-534.

[3] Carter HB. Assessing Risk: Does This Patient Have Prostate Cancer? Journal of the National Cancer Institute. 2006;98:506-507.

[4] Amundadottir LT, Sulem P, Gudmundsson J et al. A Common Variant Associated with Prostate Cancer in European and African Populations. Nature Genetics. Early Online Publication May 7, 2006.

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Tags: Prostate Cancer, Uncategorized