Identifying high-risk prostate cancer means more prudent treatment decisions

May 16 2005

While prostate cancer is a very common diagnosis, it is a deadly disease in relatively few men. One in 6 men will develop prostate cancer during his lifetime. However, of these, only one in 10 cases will be life-threatening.

Yet, since the prostate-specific antigen (PSA) screening test became widely available about a decade ago, more men than ever are receiving treatment for prostate cancer even though it's clear that not all patients benefit equally from aggressive therapy. Treatment usually begins with a prostate biopsy and can include radiation, surgery and chemotherapy.

"This is the prostate cancer paradox," said Mark Garzotto, M.D., lead study investigator. "The big question is how to decide which men have life-threatening cancer. These men need aggressive treatment. Men who don't have deadly cancer potentially may instead be closely monitored, sparing them the side effects of treatments."

That's why researchers at the Oregon Health & Science University Cancer Institute and the Portland Veterans Affairs Medical Center (PVAMC) began searching for a way to predict which men have lethal prostate cancer before a biopsy.

What they came up with is a simple chart that urologists and oncologists can use to predict whether a deadly prostate cancer tumor is present. This chart, or nomogram, will help physicians and patients identify whether aggressive cancer is present, as these men are by far the most likely to benefit from treatment.

"Our model can help predict which men may have the most aggressive type of prostate cancer and which men can relax," said Garzotto, director of urologic oncology at the PVAMC, associate professor of surgery (urology) in the OHSU School of Medicine, and member of the OHSU Cancer Institute.

An outpatient procedure that requires local anesthesia, prostate biopsy can cause patient anxiety, pain, bleeding and infection, and can lead to a significant increase in medical and nonmedical costs to health care systems and patients. Three out of 4 prostate biopsies are negative for cancer. In men with a PSA less than 10, only 9% have aggressive cancer.

Gleason score is used to define tumor grade. The Gleason score is the most commonly used prostate cancer scoring system and is considered one of the most important prognostic indicators for prostate cancer. The score is based on tissue findings throughout the prostate that correlate with the aggressiveness of a tumor. High Gleason scores are indicative of aggressive cancers and are not associated with a favorable prognosis. High-grade prostate cancer, the most lethal type, has a Gleason score of 7 or greater.

"Our nomogram identifies the men who are most likely to have high-grade tumors and are most likely to benefit from a biopsy," Garzotto said. "Knowing a patient's age and the results of a few simple clinical tests is all the information we need to accurately predict tumor grade without performing a biopsy."

Garzotto and his colleagues created the nomogram by statistically analyzing clinical variables collected prior to prostate biopsy. In the prospective study, they collected data on 1,699 men with a PSA of less than 10 ng/ml who underwent a prostate biopsy with a minimum of six samples. They analyzed the following variables: age, race, family history of prostate cancer, digital rectal exam, prostate specific antigen (PSA) values, PSA density (PSA divided by prostate volume), prostate volume, PSA doubling time and ultrasound findings. Thirty percent of data were reserved for study validation.

Through prostate biopsies, researchers found that almost 92 percent of the men were found to have no cancer or low to moderate cancer graded with Gleason scores between 1 and 6. About one-third of men with the disease had high-grade prostate cancer, which was detected in 157 subjects, or about 9 percent of the men in the study.

Researchers then used logistic regression analysis to compare clinical variables with biopsy outcomes. Researchers found they could accurately predict a tumor's Gleason score using three clinical variables: age, digital rectal exam findings and PSA density.

"We found that PSA density is by far the clinical variable most predictive of Gleason score," Garzotto said. Men who had a PSA density elevated to above 0.18 had a 24-fold greater chance of high-grade prostate cancer than men whose PSA density was low or normal.