Randomized Trials Needed to Settle Prostate Cancer Controversies

BUFFALO, NY—Prostate cancer screening protocols and treatment for localized prostate cancer are less standardized than for other cancers such as breast cancer, and treatment choices remain difficult for many men and their physicians, Jerome P. Richie, MD, said at the Surgical Oncology Symposium, hosted by Roswell Park Cancer Institute.

“Prostate-specific antigen (PSA), discovered by researchers at Roswell Park, offers physicians a dilemma. We find cancers and then argue about how to treat them,” said Dr. Richie, professor and chair, Division of Urological Surgery, Harvard Medical School and Brigham and Women’s Hospital, Boston.

Although prostate cancer is very common in older men, not all patients will die of their disease, Dr. Richie noted. “It has been shown that more than 30% of men over the age of 50 have clinical prostate cancer at autopsy. There is a clear discrepancy between prevalence and significance,” he said.

The lack of randomized clinical trials has hampered the ability to determine the true impact of the PSA test, Dr. Richie said. Unlike mammography for breast cancer and the Pap smear for cervical cancer, there has been no definitive proof of improved survival by regular screening for prostate cancer with the PSA test.

“Although use of PSA improves early detection, the test has a high false-positive rate, and we need ways to improve the test to better determine the difference between aggressive prostate cancer and benign disease,” he noted.

Dr. Richie mentioned age-specific guidelines to determine when increased PSA levels are indicative of cancer (see Table ). Use of such guidelines is controversial and may be combined with results from serial PSA tests, since an increase in PSA of 0.75 ng/mL/year is predictive of prostate cancer, he added.

Other issues surrounding PSA testing include when men should start being screened and when screening should stop. “It’s probably not efficacious to screen men who have less than 10 years life expectancy,” Dr. Richie said.

Sensitivity of PSA testing can also be improved by use of tests to measure the percentage of PSA bound to proteins in the blood and the percentage that is unbound, or free, PSA. “The lower the percent of free PSA, the more likely an elevation is to be from prostate cancer rather than benign prostatic hyperplasia. The free PSA test can eliminate approximately 30% of unnecessary biopsies without significantly reducing the detection of prostate cancer,” Dr. Richie said.

The future direction for prostate cancer researchers is to find new, sensitive markers for PSA, such as human kallikrein (hk-2), and to develop randomized treatment trials.

“Some trials have begun, but it will be 10 years before we have meaningful data. In the meantime, physicians and patients need to use multiple factors to determine the best treatment—radical surgery, nerve-sparing surgery, brachytherapy, radiation therapy, etc. We will continue to improve the treatments and decrease the morbidity, but we are still lacking critical information about this disease,” Dr. Richie said.