Short of a cure, the Holy Grail in prostate-cancer treatment is determining the cancer's aggressiveness from the start, and such a test is what a research team at the University of Pittsburgh School of Medicine has developed.
In a clinical trial whose results are published online today in the American Journal of Pathology, the Pitt team found that analysis of genetic abnormalities not only in prostate-cancer cells but also in benign tissue adjacent to the tumor and even the patient's blood accurately can predict clinical outcomes of the cancer.
Genetic abnormalities signal whether the cancer is aggressive or indolent (relatively inactive). They also can predict relapse.
The lead investigator, Jian-Hua Luo, an associate professor in the school of medicine's Department of Pathology, said analysis of "copy number variations," in the genes of tumor, benign tissue and blood cells potentially can be used to determine the cancer risk, which in turn, can determine a more confident course of treatment.
"We found that the genetic abnormality is not just limited to the cancer but adjacent tissue and in a blood sample," he said.
Genetic analysis of tumor cells reveals a greater number of variations, or "CNV," whose characteristics identify how aggressive the cancer is. Surrounding tissue and the patient's blood contains CNV to a lesser degree but in quantities sufficient to predict accurately the cancer's eventual outcome.
For now, urologists rely on the PSA test -- serum prostate specific antigen -- to indicate whether the patient might have or might develop prostate cancer. But once prostate cancer is diagnosed, doctors have no sure test to indicate how severe or potentially fatal it will be.
Doctors currently use a prostate-cancer rating system to help determine treatment. After the removal of a patient's prostate gland, if a relapse occurs, then doctors monitor how fast PSA levels double, which indicates its aggressiveness. Doubling in four months means the prostate cancer is high risk, which means potentially more aggressive treatment. It's considered indolent if it takes 15 months or longer for the PSA level to double, which could validate a wait-and-see approach.
The CNV test, by improving analysis of prostate cancer in a biopsy, would help doctors better determine a course of treatment. It also would complement the current prostate-cancer grading system, Dr. Luo said.
After reviewing study results, James D. Brooks, a professor of urology at Stanford University who wasn't involved in the research project, said the Pittsburgh project, if validated, could represent "the Holy Grail of prostate cancer" by specifying from the start whether aggressive treatment is necessary.
"It is very intriguing that they find a genetic alteration that correlates to the behavior of prostate cancer that can serve as a diagnostic test to help manage patients," Dr. Brooks said. Such tests "will help tailor a treatment to fit the patients -- less aggressive treatment in patients with the more indolent form and more aggressive in patients with more lethal prostate cancer."
The study involved genome analysis of 238 samples obtained from men undergoing radical prostatectomy, or removal of the prostate gland, along with 104 prostate tumor samples, 85 blood samples from patients with prostate cancer and 49 samples of benign prostate tissues adjacent to the tumor. Based on analysis of those results, the team used the CNV procedure to test 25 new prostate-cancer samples to verify accuracy.
The study also tested how well the CNV test predicted how fast PSA-levels doubled in patients who had had a relapse.
Dr. Luo said his team will do a more extensive clinical trial to see if predictable results of CNV hold up. In the initial study, test accuracy rates for the different cells ranged from 67 percent to 81 percent. If results in the expanded study prove equally strong, he said, he would hope the test could be used in the clinic within three years.
David Templeton: firstname.lastname@example.org or 412-263-1578. First Published May 7, 2012 12:00 AM