The May 5 issue of the Annals of Internal Medicine carried a report about some recent research looking to identify biomarkers for aggressive prostate cancer. We have been plagued with our inability to differentiate between which prostate cancers are aggressive and will kill and which are actually indolent and will not affect a man’s life. There are multiple types of prostate cancer and we are incapable of knowing which cancer is which, so treatment decisions are blinded to the eventual impact the cancer may make on a man’s life.
This is the very issue that is at the root of all the controversy pertaining to the use of PSA and DRE screening. The detractors to screening claim that we are over identifying prostate cancers and treating many men who do not need treatment. This over treatment is both very expensive and wreaks havoc on the quality of life of too many men. On the other side of the controversy are the men who know their lives would have been cut short if it were not for their monitoring their PSA scores along with DRE exams.
The research discussed evaluated three molecules that are commonly associated with prostate cancer, bcl-2, a molecule that helps regulate cell death; p53, a protein produced by a tumor-suppressor gene; and micro vessel density. The researchers hope is that these molecules might serve as markers that could discern which tumors are potentially life threatening and would need aggressive treatment as opposed to those that could simply be monitored.
“We’re not trying to say these are the only markers,” said study author Dr. John Concato, a professor of medicine at Yale University and director of the clinical epidemiological research for the Veterans Affairs Connecticut Healthcare System. “This is a proof of principle.” He went on to say that measuring levels of the markers might someday help guide treatment of men with prostate cancer. “If the markers are positive, that might be an indication that more aggressive therapy is indicated,” Concato said.
As we have come to expect in the world of prostate cancer, Dr. Concato’s statements have been challenged in an accompanying editorial by a cancer specialist, Dr. Edward P. Gelmann, chief of the division of hematology/oncology and deputy director of the Herbert Irving Comprehensive Cancer Center at Columbia University. A number of previous studies have shown that results of p53 tests “are not reproducible from one laboratory to the next,” Gelmann said. “There is great variability in both technique and results.” Though p53 has been studied as a biomarker for a number of cancers, he said, it is used only for one rare malignancy, transitional cell carcinoma of the blood.
As for bcl-2, Gelmann said that the number of cases in the study with a positive reading was too small to provide proof of its predictive power. “To prove it has prognostic significance would require would require a larger trial,” he said.
Dr. Concato’s findings stemmed from an examination of tissue samples from 1,172 men diagnosed with prostate cancer at VA centers in New England. Researchers looked at biomarkers and identified these three as associated with a higher risk of death from the cancer: bcl-2, a molecule that helps regulate cell death; p53, a protein produced by a tumor-suppressor gene; and micro-vessel density, the excessive production of blood vessels needed for growth of a cancer. Levels of all three markers were significantly higher in the men who died of prostate cancer in the subsequent 11 to 16 years, the study found.
Concato has proposed a clinical trial that “would treat patients based on marker status, as positive or negative.”
So, once again the bottom line is that we are caught chasing our own tails. Maybe one day we will manage to catch our tail.
Joel T Nowak MA, MSW