April 26, 2010

Biomarkers predict who may need prostate treatment

A blood test for certain forms of prostate specific antigen, or PSA, and measurement of DNA content in biopsy tissue accurately predict which men with potentially nonlethal prostate cancers may eventually need treatment, say Johns Hopkins scientists.

“Our goal is to develop new biomarkers to select the right patients for the right therapy and know when the therapy should be delivered,” says Robert Veltri, associate professor of urology and oncology at the Johns Hopkins Brady Urological Institute, who adds that up to half of prostate cancer patients with low-grade, low-stage disease could safely be monitored rather than treated aggressively.

To make their prediction calculations, Veltri and his colleagues evaluated two tests on 71 men enrolled in a Johns Hopkins Proactive Surveillance program to monitor their small, low-grade cancers, none of which could be felt on physical examination. The first is a blood test that combines three forms of PSA and is called the prostate health index (phi), which was developed by Beckman Coulter and is not FDA-approved. The second test involves examining biopsy tissue for the amount of DNA in cells; normal cells contain precisely two chromosomes, while the number of chromosomes in cancer cells varies.

Results show that the prostate health index was higher in 39 men whose annual biopsy showed worsening prostate cancer. Also, in these men, abnormal DNA copies in cells from biopsied prostate tissue were overexpressed in cancerous areas as well as in adjacent noncancerous areas. The median time for following the study participants was about three and a half years.

“There are no outward signs that these small prostate cancers may be progressing—men clinically feel the same, and physicians are not likely to detect it on conventional imaging scans,” Veltri says. “We believe that close monitoring with the right biomarker tools may help to detect this shift in pathological stage.”

Veltri plans to continue studies with a larger group of patients over a longer time period. He is also studying other biomarkers that include other types of PSA and the shape of nuclei in cells.

Funding for the study was provided by Early Detection Research Network and SPORE Prostate Grant of the NCI and the Patana Fund. Other participants were Sumit Isharwal, Lori Sokoll, Patricia Landis, Jonathan Epstein, Alan Partin and H. Ballentine Carter, all of Johns Hopkins; Danil Makarov, of Yale University; and Cameron Marlow, of the Johns Hopkins University Cell Core Facility.

The findings were presented at the 101st annual meeting of the American Association for Cancer Research, held April 17 to 21 in Washington, D.C.