Rethinking the PCPT: New panel convening

February 1, 2005

Chicago--A panel of experts is expected to convene to reconsider the controversial findings of the Prostate Cancer Prevention Trial (PCPT), in particular, the indication that finasteride (Proscar) may prevent prostate cancer and yet lead to more severe grades of cancer in those men who develop it.

Reinterpreting the results of the PCPT may take on a greater significance if upcoming studies on the efficacy of supplements in preventing prostate cancer-such as the Selenium and Vitamin E Cancer Prevention Trial (SELECT)-show limited success, as have past studies on selenium and vitamin E, which indicated that the supplements helped prevent prostate cancer, but only in smokers.

The PCPT clearly demonstrated that finasteride lowered the rate of a man developing prostate cancer. Considering that prostate cancer is the cause of death in 3% to 4% of men, a 25% reduction in the incidence of cancer could have a tremendous effect on mortality, said Judd W. Moul, MD, professor and chief, division of urology, Duke University Medical Center, Durham, NC.

The PCPT, which finished a year-and-a-half ago, compared finasteride with placebo in more than 18,000 men. Over 24% of men in the placebo arm had developed prostate cancer by the end of the 7-year study, compared with slightly over 18% of those in the finasteride arm, Dr. Moul noted.

However, the results were considered disappointing by many physicians because 6.4% of the men had developed prostate cancer with a Gleason number of 7 or greater in the finasteride arm, compared with only 5.1% in the placebo arm.

Also of interest, the PCPT indicated that sexual adverse effects were slightly more common in the finasteride arm, whereas finasteride seemed to show utility for preventing urinary retention and other BPH symptoms.

Dr. Moul said it was unlikely another large trial of finasteride for preventing prostate cancer would ever follow the PCPT, which was sponsored by the National Cancer Institute.

"The drug is getting too close to its patent expiration-Merck only has a year or 2 left," he said.

Possible flaws Still, the expert panel, currently being convened by the NCI, should reappraise the study's findings, Dr. Moul said. He noted that the grade of cancer was a secondary, not a primary, endpoint, and suggested a number of potential flaws that might have skewed the data.

The trial was limited to men age 55 years and older, 92% of whom were Caucasian, Dr. Moul said, and 84% of whom had had an initial PSA of less than 2.0 ng/mL.

One possible source of bias was the manner in which biopsies were conducted, he said.

"Biopsies were to be done when the 7-year study ended, but many refused end-of-study biopsies, and some were lost to follow-up. If the study were done today with a local anesthetic, many patients might be more willing to get the biopsies. The for-cause biopsies for elevated PSA levels were significant, because they were like our real-life practice cases, unlike the more artificial end-of-study biopsies," said Dr. Moul, who helped enroll more than 80 patients in the PCPT at Walter Reed Army Medical Center, Washington.

The results were also surprising considering that finasteride has been approved for some time for BPH. Patients in the PCPT were tested on the same dose used for BPH, 5 mg per day.

"Finasteride is a chronic medication. For BPH, you would use it continuously for the rest of a patient's life if it's working. Longer-terms studies show the effect on BPH is quite durable. A third to half get good results, but we know the prostate will grow back if you stop taking the drug," Dr. Moul said.