Medical Device Link.

Originally Published IVD Technology July 2004

INDUSTRY NEWS

Table I. Relationship of the prostate-specific antigen (PSA) level to the prevalence of prostate cancer and high-grade disease. Source: The New England Journal of Medicine 2004 (click to enlarge).

Manufacturers developing tests for novel prostate cancer markers may be emboldened by the findings of a study examining the conventional prostate-specific antigen (PSA) test. In this study, a significant portion of men whose PSA levels fell in the normal range were found to have prostate cancer. 

The study, conducted by Thompson et al. and published in the May 27, 2004, issue of the New England Journal of Medicine, revealed that 15% of men with normal PSA levels (i.e., PSA values of 4.0 ng/ml or less) had prostate cancer. In addition, 15% of those with the disease were found to have high-grade cancers. 

The prevalence of cancer increased as PSA level increased, with 27% of the cancers found in men whose PSA levels were 3.1 to 4.0 ng/ml. In addition, the severity of disease increased as PSA level increased, with 25% the high-grade cancers found in men with PSA levels between 3.1 and 4.0 ng/ml (see Table I. The authors of the study conclude that “there is no PSA level below which a man can be assured that he has no risk of prostate cancer.”

If the PSA test, the test that is most widely used to screen for prostate cancer, misses a number of treatable cancers, what then? Some may argue for a reassessment of the limits of the normal range for the test. In a commentary accompanying the study, H. Ballentine Carter, MD, suggests that lowering the threshold may be appropriate for select cases. Carter says, “a threshold of 2.5 ng/ml seems reasonable for men below the age of 50.”

However, Carter does not advocate changing the threshold for all men. He says, “the use of higher PSA thresholds risks missing an important cancer . . . whereas the use of lower PSA thresholds increases not only unnecessary biopsies but also the proportion of biopsies that identify clinically insignificant disease.”

Although he is not in favor of adjusting the conventional PSA test, Carter acknowledges that doing so would be beneficial to detect the high-grade cancers missed by the PSA test. In order to catch these cancers, he recommends developing tests for new biomarkers rather than relying on PSA “because high-grade cancers produce less PSA than low-grade cancers.”

Promising tests for alternative prostate cancer markers are in development. Researchers at the Institute of Cancer Research Everyman Centre (London) have identified the E2F3 gene, which may lead to a test that can identify aggressive prostate cancers. Tessera Inc. (Seattle) is developing another test, which identifies a protein called early prostate cancer antigen (EPCA). A study of EPCA at the University of Pittsburgh indicated that EPCA might enable practitioners to detect the disease five years earlier than other accepted testing methods can. 

In addition, researchers at both Johns Hopkins University (Baltimore) and the University of Michigan (Ann Arbor, MI) found AMACR (a gene that triggers the production of proteins specific to cancer cells) to be a strong marker for prostate cancer. Another test is being developed by Matritech Inc. (Newton, MA). Researchers there have found that this NMP48 blood test is more sensitive and specific than the PSA test and may be able to rule out patients with benign prostate disease. Lastly, Gen-Probe (San Diego) and DiagnoCure (Toronto) are codeveloping a urine-based prostate cancer diagnostic that tests for a gene known as PCA3DD3.

If some of these tests deliver on their promises for earlier or more-sensitive and-specific detection of prostate cancer, manufacturers of PSA tests may soon find some new competition on the market. 

Copyright ©2004 IVD Technology